Health Benefits of Tea for Fibromyalgia and Arthritis – The Mighty

Health Benefits of Tea for Fibromyalgia and Arthritis

Quench your thirst while enjoying the health benefits of tea. How tea may improve living with fibromyalgia and arthritis.

There are many health benefits of tea. As long as you are not sweetening it with sugar/honey, or adding milk, it is calorie-free. This is great for anyone watching their weight, but the benefits don’t stop there.

For people like me who live with painful and chronic inflammation from fibromyalgia and arthritis, tea is one of the best beverage choices we can make. Tea is easy to make and can be enjoyed all day long.

Keep reading to discover the various types of teas and their health benefits.

Disclaimer: This blog post contains affiliate links. I may earn a small commission to fund my coffee drinking habit if you use these links to make a purchase. You will not be charged extra, and you’ll keep me supplied in caffeine. It’s a win for everyone.Advertisements

Health Benefits of Black, Green, and White Teas

Black, green, and white teas all have one thing in common. Each one is known for its anti-inflammatory properties. This is great news for those of us doing everything we can to reduce how much inflammation our bodies experience from chronic illness. If that isn’t enough, here are some more health benefits to these popular teas.

Black Teas

Black teas come from the Camellia sinensis plant. They are often blended with other plants to create a variety of flavors. Popular black teas include Earl Grey and chai. While a glass of black tea has less caffeine than a cup of coffee, it contains more caffeine than other teas.

When consumed regularly the health benefits of black tea include but are not limited to:

  • Reduction of inflammation
  • Reduced cholesterol 
  • Improved gut health
  • Reduced blood sugar levels
  • Improved heart health
  • Lower blood pressure

Green Teas

The biggest benefit of green tea is its catechin content. These antioxidants fight cell damage. Brew your next cup of green tea in water with a temperature range of 160-170 degrees. Boiling water is bad for catechins. To increase absorption of catechins, add lemon, and skip the milk as it makes them harder to absorb.

When consumed regularly the health benefits of green tea include but are not limited to:

  • Improved blood flow
  • Lowers cholesterol
  • Improved memory
  • Reduced inflammation

White Teas

Tea that is not processed after drying is called white tea. This gives it a milder flavor compared to black and green teas. It contains tannins, fluoride, catechins, and polyphenols. These compounds are responsible for the various benefits this tea provides.

When consumed regularly the health benefits of white tea include but are not limited to:

  • Reduced inflammation
  • Repair and recovery of damaged skin
  • Improved oral health
  • May help control diabetes
  • Decrease blood pressure
  • Antibacterial properties

Health Benefits of Herbal Teas

Instead of being brewed from the tea plant, herbal teas are made by steeping herbs, flowers, or roots. Herbal teas do not contain caffeine and their health benefits vary depending upon the blend used.

Options for specific health concerns

Improved digestionDandelion, chamomile, cinnamon, peppermint, and ginger teas are great for reducing indigestion, bloating, and vomiting.

Boosting immunityElderberry, echinacea, ginger, and licorice root teas are known for their antioxidants and vitamins that fight disease and infection.

Reduced inflammation: One of the best inflammation-busting herbs is ginger which makes it the ideal tea for people with arthritis and fibromyalgia.

Stress and anxiety reduction: Stress and anxiety can increase pain from inflammatory illnesses. Chamomile tea can help relieve stress and help you sleep better.

Lower blood pressure: Herbal teas such as Hibiscus can decrease blood pressure.

Word of Caution

Always talk to your doctor before beginning any form of treatment for your chronic illness. Some ingredients and plants may cause a negative reaction with your current medications or trigger an allergic reaction. Because of my lemon allergy, I have to avoid all tea blends that include lemongrass. Not knowing every ingredient can be dangerous.

What It’s Like to Reflect on Past Seasons of Suicidality – The Mighty

Illustration of a young woman's face, shy and scared
Suicide

What It’s Like to Reflect on Past Seasons of Suicidality

Lydia Joy Launderville  •  FollowSeptember 9, 2021


Editor’s Note

If you experience suicidal thoughts, the following post could be potentially triggering. You can contact the Crisis Text Line by texting “START” to 741741.

I was suicidal for a period of six months three years ago. It was due to traumatic experiences coming to the forefront of my memory, specifically saving my mother from suicide when I was just a child. Trauma was all around me, in my family, in the people I talked to on a daily basis, in the stories I read and in the work I was doing. Eventually, all of that trauma caught up with me and my mental health suffered immensely.

It was having a suicidal person contact me and getting them help, only for them to refuse it in the end, that triggered those hidden memories to seep back into the front of my mind. I would disassociate during the middle of my day, brought back to the moment my parent nearly ended her life if I hadn’t stepped in to stop her. This triggered six agonizing and grueling months of intrusive thoughts of all things to do with suicide. It got to the point I could not even handle hearing the word “suicide” without spiraling emotionally.

It was a very scary and lonely time. I didn’t know what was going on. I didn’t know it was post-traumatic stress disorder (PTSD) making a bigger entrance into my life and that I wasn’t actually suicidal, but rather, experiencing emotional flashbacks. I did not realize at first it was traumatic memories coming unlocked, those blocked memories that can appear out of nowhere, but are often triggered by a stressful time or crisis. That was true for me. Months of depleting myself and one crisis after another sent me spiraling, not to mention all the ways I wasn’t taking care of my physical health.

I had to step back from my daily responsibilities to make myself and especially my mental health a priority. I turned down triggering conversations, went to nature, grounded myself in the present, left the dark alleyways of trauma and abuse behind for days at a time to focus on the future. It was difficult, traversing triggers countless times a day, and coming back from it emotionally and mentally, even physically. With time, it got easier and then I noticed with self-care, working on my physical health and getting more sleep (I was sleep deprived often during that time), I found my mental health drastically changed, and for the better.

I’m a completely different person three years later. For one, I’m in cognitive behavioral therapy (CBT), have worked on my health all around and have stepped out of the darkness of trauma and into the light of recovery. Now, a suicidal thought comes in passing and only triggered with a severe crisis. To be honest, I have only had the thought of, “I don’t want to be here” maybe once in three years since those very difficult six months of my life. And, say if it did return, if a period so dark and difficult like those six months showed up again, I have a plan in place with my support system and therapist.

It’s difficult for me to say I’m thankful for those dreary days, difficult nights and terrifying moments, but I have found it has helped me understand those who battle with suicidal ideation more on a deeper level. I have more understanding, compassion and overall knowledge on this subject now, and knowledge is wealth.

That difficult time was also a way of my brain and body telling me I needed to take care of myself, and that has been a lesson I have carried with me ever since. It was not lost on me I had put everything and everyone first pending that tough time. I was depressed leading up to that, surrounded by traumatic details and soul shattering realizations. I was bouncing from one crisis to another, and ones not made of my making. I was simply along for the ride, begging it to end. It ended when I took control over what I could control: Eating healthier, getting more sleep, focusing on self-care and so much more.

I’m so thankful to be living a life I want to be alive for. Even on the hard days, even when I hear people say, “How do you live with all of that?” I know down deep in my heart of hearts the beautiful days that were ahead of me three years ago were so worth it. I can’t wait for the next three years, the next three after that and even more to come. I was meant to be here and so are you.

Resources

If you or someone you know needs help, visit our suicide prevention resources.

If you need support right now, call the National Suicide Prevention Lifeline at 1-800-273-8255, the Trevor Project at 1-866-488-7386 or reach the Crisis Text Line by texting “START” to 741741.

We want to hear your story.

How to Start Meditating: A Step by Step Guide – Jan Murdo, CMSC, CMT – Migraine Again

By Jan Mundo, CMSC, CMT

PreventionBehavioral Therapy

How to Start Meditating: A Step by Step Guide

By Jan Mundo, CMSC, CMTLast Updated: Apr 10, 2019

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Fact-CheckedHow to Start Meditating: A Step by Step GuideUnsplash

An excerpt from The Headache Healer’s Handbook by Jan Mundo, CMSC, CMT

Have you ever noticed that you can relax in front of the TV and rest your bones, but not necessarily feel refreshed? Who knew that relaxation was a skill?! Meditation is both the same as and different than simply doing nothing.

Research studies over the past fifty years have confirmed what ancient Eastern traditions have known for centuries: meditation is good for you. In the 1970s Herbert Benson, MD, found that meditation lowers stress, blood pressure, muscle tension, heart rate, and breathing rate. Recent functional magnetic resonance imaging (fMRI) studies have shown that meditation can alter brain-wave states and pain.

Jon Kabat-Zinn, MD, founder of the Mindfulness-Based Stress Reduction (MBSR) Clinic at the University of Massachusetts Medical School, has pioneered MBSR classes and training as part of medical treatment, and his research shows its beneficial effects. Meditation classes are also becoming more widely accepted and available in health and wellness settings for people with cancer, stress and anxiety, chronic pain, addiction, illness, and disease.

Meditating can elicit the kind of relaxation your body and mind crave. You become present, focused, and aware, and you start to notice what is within and around you. You feel rejuvenated and not just running on the proverbial “treadmill of life” in your head. Once you are adept at mindfulness, calming your mind for even five minutes can feel like a mini-vacation.

Cultivating a Practice

Meditation is a skill you master with practice, and, although physically you are “just sitting,” it is very different than doing nothing. The difference lies in where you place your attention, and how you use it.

Meditation can seem hard, and many people say they are not good at it, but that’s because while we’re doing it, life comes up. We think about and remember people, places, and things; and we plan. Emotions and memories bubble up. And then we return to the breath. And again and again.

As you practice over time, you will get better at noticing what comes up and letting your mind settle into a peaceful state. It’s not that your troubles disappear but that your relationship to them and the pull they exert can lift and soften into “being with what is.”

As with almost everything, practice makes it easier.

Notice I didn’t say, “practice makes perfect”! Perfection implies that you are striving to achieve something. In meditation, striving for perfection takes you away from simply being in the moment. Rather than attaining enlightenment or entering into some other state of being, somewhere else, mindfulness is about paying attention in the here and now.

Because thoughts naturally keep arising, sometimes people get discouraged about their inability to meditate, as if it’s a talent only some people are born with. They abandon their practice, reporting that they “can’t do it very well” and feeling as if they’ve failed. I often hear this from clients when I begin working with them. This frustrating predicament is actually the best reason to keep going. A practice of returning to the present in your body is a core skill of working with headaches and their associated pain.

The instructions for mindfulness meditation are simple: Pay attention to your body and your breath as you breathe in and as you breathe out — and return your attention to your breath if your mind wanders. And yet mindfulness is more than sitting on a cushion and following the breath. It is a practice of being awake to life in each moment.

Mindfulness Meditation Setup

This section will help you prepare a place to sit that supports your posture in keeping a straight back and staying alert. Read through the entire section before you begin.

Seating

You can sit on a meditation cushion or in a chair, whichever you find most comfortable. This might vary, depending on whether you are at home, in an office, riding on a train, traveling, or in other settings.

With knee or other issues, sitting on a cushion or the floor can be difficult. It’s fine to use a chair if you prefer.

If you cannot sit, you can lie on your back, arms by your sides, palms facing up.

In a chair: Have your feet flat on the floor, hip-distance apart, toes facing forward. Scoot forward in the chair, with your thighs parallel and your legs perpendicular to the floor, so your feet make solid contact with it.

On a cushion: Sit with your legs crossed or in half-lotus or full-lotus position. In half-lotus, one foot is placed on the opposite thigh; in full-lotus, both feet are placed on opposite thighs.

  • A zafu, or firm, kapok-filled meditation cushion, provides a supportive way to sit on the floor because it raises your seat and hips higher than your legs and keeps your back straight, posture aligned, and mind alert. (Some people do cross-legged postures in a chair or on a firm couch. Here too, use a cushion to raise your hips.)
  • To cushion your knees and feet, you can place the zafu on a zabuton, a flat, rectangular pad, or just use a folded-up blanket.

Once you’ve chosen your seat, align your ears, shoulders, and hips vertically. Proper alignment helps you settle into gravity, reduces upper body tension, and promotes breathing and alertness.

Feel your seat on the chair or cushion, settle in, and let gravity hold your weight, rather than pulling up and away from it.

Hand Positioning

Position your hands in one of two ways:

  1. Fold your hands together in your lap by placing one over the other and interlacing your thumbs (but don’t interlace your fingers). It doesn’t matter which hand is on top; whatever feels best.
  2. Or, place your hands palm up on your thighs. (I advise against a palms-down position because people tend to grip.)

You Can Use Props

“You can use props, you know,” my meditation teacher assured me. What a relief.

There is no reason to be uncomfortable or suffer pain during meditation. For instance, if your knee sticks up and your thigh and hip joint need support when you’re sitting cross-legged on a cushion, wedge a small pillow underneath your knee and/or thigh, so they can rest comfortably.

If your arms feel “too short,” place a pillow in your lap, whether you’re using a chair or a cushion, to support your hands and arms and reduce shoulder strain. When seated in a chair, you can place a small pillow or rolled-up blanket below your waist to support your back if needed. Sitting under your own power instead of leaning against the chair will strengthen your back and core muscles over time.

Every body is different. What is comfortable for you might not be comfortable for someone else, and even what’s comfortable for you can vary over time, especially if you have a physical challenge or an injury, or are recovering from an injury. Make modifications as necessary whenever your body needs support.

Mindfulness Meditation Instructions

Now that your body is in position, you’re ready to begin. Read through these instructions first, and before you start, set a timer for twenty minutes, so you don’t have to keep checking the clock.

  • First take three full, relaxing breaths and release each with an “ah” sound. Notice where and how you breathe (chest, stomach, or both? shallow or deep?), and pay attention to the quality and mood of your “ah” (loud or soft? relieved or tired?).
  • Now rest your tongue on the roof of your mouth and let your teeth slightly part to soften your jaw.
  • Close your eyes and focus your attention on your breath as you inhale and exhale naturally.
    • Breathe through your nose, if possible, to warm and filter the air and not parse the breath.
    • Focus your attention on the filling and emptying of your lower abdomen, below your belly button. Breathe as if a balloon is gently inflating and deflating with each breath.
    • Let your breathing be easy and circular, without any holding between the inhale or exhale.
  • When your mind wanders, bring it back to your breath. (It may have been drawn away by a thought, a pain, a noise, or something else.)
    • You might notice your attention wandering within the first seconds of the practice, or just a minute before it ends.
    • Whenever you notice your mind wandering, no matter when or how many times during your practice, return your focus to your breathing.
  • To complete your practice after the timer goes off, let your eyes come open slowly and let the world come to you.
  • Check in with yourself to see what is different. How do you feel, compared to when you started? What do you notice? If you feel calmer and less tense in body and mind, note your feelings and sensations. If you were in pain when you began, has the pain shifted?
  • Meditate for twenty minutes, five days per week if possible.

You now know how to meditate, a practice that can set the tone for your day and help you find calm in the midst of chaos and decompress when it is over. You can practice anytime, anywhere, by simply remembering to stop, breathe, and pay attention. Remember to add the time and duration of your practice to your Headache Diary.

Special Instructions for Working with Pain and Other Sensations

In daily life, we might try to ignore, numb, or retreat from the feelings or sensations that make us feel uncomfortable. As in the story of my burning shoulder, meditation gives us an opportunity to work with our pain and discomfort by moving our attention toward it.

When you notice pain or other sensations, bring your attention there, and try to describe what you feel. Keep staying with your sensations and see what happens. Do they get stronger or weaker? Do they change in shape or size? Do they reveal other sensations or emotions as you pay attention?

Keep focused on whatever emerges and happens as a result. When the sensations subside or no longer grab your attention, return to following your breathing.

The Headache Healer's Handbook

Here’s how:

  • When sensations arise, focus on them.
  • Name the sensations. For example, pain, tingling, itching, pulsation, burning, numbness, stabbing, hot, cold, heavy, light.
  • Describe the sensations in the following ways:
    • size and shape (length, width, depth; on the surface or deep inside; structure; anything else)
    • intensity (more or less, stronger or weaker)
    • qualities (for example: feels like a brick, a cord, a sheet-metal plate, a piece of plywood, a bubble; is steady or pulsing, hard or soft, hot or cold)
    • location (stationary or mobile; stuck, travels, or moves from one side to another)
  • Keep following your sensations until they dissipate. Do other sensations, like pain or discomfort, come to the fore? If so, then work with them.
  • Do memories, thoughts, or emotions emerge? If so, is there a connection?
  • After what you are working with subsides, return to following your breathing.

It is fascinating to discover by direct experience that your pain is not necessarily fixed. It can move and morph when you focus your curiosity and attention on it.

Notes:

  1. Thích Nhâ ́t Hanh, Touching Peace: Practicing the Art of Mindful Living (Berkeley, CA: Parallax Press, 1992),
  2. Sylvia Boorstein, “When the Going Gets Tough, the Tough . . . Meditate: Spiritual Practices to Calm the Mind and Support the Heart during Diffi- cult Times” lecture, with Sylvia Boorstein and David Ingber, Sparks: Live Conversation Series, New York, June 1, 2016, romemu.org.

Excerpt from the book The Headache Healer’s Handbook: A Holistic, Hands-On Somatic Self-Care Program for Headache and Migraine Relief and Prevention. Copyright © 2018 by Jan Mundo. Printed with permission from New World Library. http://www.newworldlibrary.com


Find out more about Jan Mundo’s work at www.theheadachecoach.com

25 Things People Living With Chronic Pain Wish Others Understood – The Mighty

25 Things People Living With Chronic Pain Wish Others Understood

The Mighty Staff  •  FollowFebruary 16, 2016


If you’ve never experienced life with chronic pain, it can be hard to understand what it’s really like. Unfortunately, this sometimes leads to a lack of support — and even a lack of empathy — for people going through it.

We reached out to people in our Facebook communities who live with chronic pain and asked them to share one thing they wished others understood about their condition. After reading the responses, the need for increased awareness, validation and overall kindness is obvious.

Here are just some of the things people with chronic pain want you to know:

1. “It’s real.” — Marcia A Johnson

2. “Even on a really bad day, I do as much as I can. I smile, I try to look as human as possible! I try to hide how I am feeling both to stop you from feeling uncomfortable and help me feel better. This does not mean the pain is not there, and even though I have been doing this for years, it is tiring, hard and frustrating. So please try to understand, and think before you make a flippant and hurtful comment.” — Nicky Treagus

3. “Yes, just touching me hurts.” — Stephanie Horton

4. “If I back out on plans at the last minute, I’m not flaky. I just can’t predict how I’m going to feel day to day.” — Brandy Horrell

5. “Please know I appreciate your concern and caring, but I don’t need to know about the ‘latest cure’ or your questions about ‘have you tried this vitamin or that breathing exercise’ for my illnesses. Believe me, I’ve tried them.” — Zoann Murphy

6. “I absolutely do not want your pity. What I do want is your love and acceptance.” — Angie Glenn

Pink heart background with text "I absolutely do not want your pity. What I do want is your love and acceptance." Angie Glenn

7. “Being at work doesn’t equal being ‘healthy’ or pain-free. Yes, physically and externally I am at work, but on the inside, I am engaged in an all-out war to handle doing what I have to do.” — Tabitha Hodges

8. “‘Faking it’ is harder than you think.” — Ashley Mould

9. “Just because I’m 18 doesn’t mean I’m ‘too young’ to be chronically sick. It can happen at any age.” — Rose Hymers

10. “My use of pain meds is not an addiction or a leisurely pastime. It is a necessary survival tool so I can get through my day and live the life I deserve.” — Kate Sytsma

11. “It’s not all in my head. Just because you can’t physically see my pain doesn’t mean it isn’t there.” — Tierra Sprague

12. “‘Well, you look great!’ is not an acceptable answer when I tell you I’m not doing well.” — Nicki Finlayson

13. “Chronic pain doesn’t only involve pain. Insomnia, nausea, vomiting, depression, brain fog, irritability and more are also par for the course.” — Shayna Leeds

14. “When we have a bad day, please be patient and know it doesn’t last forever. We want to have good days, too.” — Cindy Garden

Storm clouds on ocean with text "When we have a bad day, please be patient and know it doesn't last forever. We want to have good days, too.” - Cindy Garden

15. “My pain level can change hourly.” — Mary McCabe

16. “If you think it’s annoying hearing about it, try living it! ” — Tracy Boyarsky Smith

17. “Don’t be mad at me because I can’t be the person I was before. Don’t judge me because I can’t work anymore. Don’t assume I’m lazy. I do the very best I can with the cards I’ve been dealt.” — Patricia Howarth Andersen

18. “You may forget I’m in pain after a while, but I can’t ever forget.” — Haylie Stewart

19. “Chronic means persistent, longterm. It doesn’t just go away. It’s always there. Some times are better than others, but the pain is always there.” — Rachel Higginson

20. “Just because you’ve lived with it for years doesn’t mean the pain is any less over time. You just adapt [and find] new ways to survive it.” — Valma Ashpaugh

21. “If thinking ‘positive thoughts’ would make it go away, I’d already be pain-free.” — Terri Johnson

Woman excitedly in front of chalkboard which has a quote bubble drawn with text "If thinking positive thoughts would make it go away, I'd already be pain-free."

22. “I can’t always keep up with you or work as fast as I’d like to.” — Rhonda Lynn Walker-Trayers

23. “Just because I did something one day doesn’t mean I can do it the next. I can’t plan my good and bad days. But please don’t stop asking me to be included in things, just understand when I just need to rest and be OK with it.” — Tommy Sorg

24. “Every single day is a battle. We just hide it better on our ‘good’ days.” — Marie Oberempt

25. “I’m not seeking attention, drugs, sympathy or special treatment. All I’m seeking is understanding and acceptance, just like anyone else.” — Faith Merryn

What would you add to this list? Share with us in the comment section below.

Editor’s note: Some answers have been shortened for brevity/clarity. These answers are also based on personal experience and shouldn’t be taken as professional advice. Talk to your doctor before starting on any medication.

The Mighty Staff  •  Follow

Friday Morning Inspiration – Marian Griffey

Good morning, everyone ~

It’s only 1:48a.m. as I start this week’s email. The household is sleeping, the neighborhood is silent, and just for now I can pretend that the whole world is at peace. I’m glad to be awake/experiencing such a momentary good feeling, having easy thoughts in my mind.

Stream late night drive by dLWilliam | Listen online for free on SoundCloud

Each time I wake, my first thought is: “Still here!” There have been numerous times since the second week of September that I doubted I would still be here at morning’s light. Many more times I would have chosen not to be. In my lifetime, I have been raped, beaten, mugged, drugged without my consent. I have experienced natural childbirth, broken bones, strangulation, and countless heart breaks. Life brings us to our knees in many ways, drags us to the edge of death, exposes us to the many ways in which humans can/do die. My experiences have been mild compared to many others; yet, the thought/feeling of death as a way to escape indescribable pain remains the same for all humans.

I'm Still Here Poem on Encouragementpraise by Louse Dance | Etsy

“Still here” may not be so homogenous. I’ve read stories, first-hand accounts from survivors of holocaust, genocide, uprising, slavery from every corner of the globe/from people of all color/race/creed. The locations/circumstances may differ; the thoughts/feelings are strikingly similar.

To be captured by pain, held captive by disease/injury, subjected to brutality of body/mind/spirit is a common theme throughout human history. So too the theme of love/kindness/compassion. Sometimes, the two themes are the same “coin” of human nature, inseparable.

The author Terry Tempest Williams states in her book, “Red — Passion and Patience in the Desert”: “The landscape that makes you vulnerable, also makes you strong.”

In that very personal, inner landscape of pain, even the strongest amongst us can be brought to vulnerable landscapes of thought/feelings. Surviving, however, is not the same thing as thriving. Only when we know/feel/believe that we are thriving do we feel strong inside ourselves. Sometimes, if not always, in order to know/feel/believe in our strength/thriving, we need outside validation.

Moving Caregivers from Surviving To Thriving

Through my own personal ordeal with almost constant pain for the past 4 months, validation from others has been the power to keep me “still here”. You, my beloved tribe of family/friends, have provided that. To say “thank you” seems woefully inadequate in balancing out the scales of equity. Thank you, one-n-all! I’m “still here” and beginning to think/ feel stronger. It’s going to be at least several weeks or months more before full recovery. Celebrate the baby-steps with me as this journey continues. As my dad would say: “We’re all put here on Earth to help each other.” Thanks for propping me up!

Thank You Images, Stock Photos & Vectors | Shutterstock

Included in that list of “thank you” recipients, I need to acknowledge the outreach support of the ACPA home office. Not only has the website offered many articles (theACPA.org), but also several staff members have stayed in contact via email/Facebook. My supervisor, Scott Farmer, is starting a virtual group available to any support group member nationwide. No one needs to suffer alone/in silence. There are others ready/willing to help prop up anyone in need of feeling stronger than their pain, needing to think/feel again that vital spark of thriving despite life’s challenges.

The landscape of pain that makes us vulnerable, is also the landscape peopled with support to help us feel strong again. Strong enough to say: “Still here!” with a tone of gratitude.

I know there are some members of our Group who do not have access to email. If you know someone in that category, share a printout of the weekly mass email with them. Call or text them with the topic of the week, inviting a discussion. It’s one way to help others remember that they are “still here”, part of this most wonderful tribe. In these uncertain times, having a tribe to call one’s own can make all the difference between surviving and thriving.

Good morning, everyone ~

It’s only 1:48a.m. as I start this week’s email. The household is sleeping, the neighborhood is silent, and just for now I can pretend that the whole world is at peace. I’m glad to be awake/experiencing such a momentary good feeling, having easy thoughts in my mind.

Each time I wake, my first thought is: “Still here!” There have been numerous times since the second week of September that I doubted I would still be here at morning’s light. Many more times I would have chosen not to be. In my lifetime, I have been raped, beaten, mugged, drugged without my consent. I have experienced natural childbirth, broken bones, strangulation, and countless heart breaks. Life brings us to our knees in many ways, drags us to the edge of death, exposes us to the many ways in which humans can/do die. My experiences have been mild compared to many others; yet, the thought/feeling of death as a way to escape indescribable pain remains the same for all humans.

“Still here” may not be so homogenous. I’ve read stories, first-hand accounts from survivors of holocaust, genocide, uprising, slavery from every corner of the globe/from people of all color/race/creed. The locations/circumstances may differ; the thoughts/feelings are strikingly similar.

To be captured by pain, held captive by disease/injury, subjected to brutality of body/mind/spirit is a common theme throughout human history. So too the theme of love/kindness/compassion. Sometimes, the two themes are the same “coin” of human nature, inseparable.

The author Terry Tempest Williams states in her book, “Red — Passion and Patience in the Desert”: “The landscape that makes you vulnerable, also makes you strong.”

In that very personal, inner landscape of pain, even the strongest amongst us can be brought to vulnerable landscapes of thought/feelings. Surviving, however, is not the same thing as thriving. Only when we know/feel/believe that we are thriving do we feel strong inside ourselves. Sometimes, if not always, in order to know/feel/believe in our strength/thriving, we need outside validation.

Through my own personal ordeal with almost constant pain for the past 4 months, validation from others has been the power to keep me “still here”. You, my beloved tribe of family/friends, have provided that. To say “thank you” seems woefully inadequate in balancing out the scales of equity. Thank you, one-n-all! I’m “still here” and beginning to think/ feel stronger. It’s going to be at least several weeks or months more before full recovery. Celebrate the baby-steps with me as this journey continues. As my dad would say: “We’re all put here on Earth to help each other.” Thanks for propping me up!

Included in that list of “thank you” recipients, I need to acknowledge the outreach support of the ACPA home office. Not only has the website offered many articles (theACPA.org), but also several staff members have stayed in contact via email/Facebook. My supervisor, Scott Farmer, is starting a virtual group available to any support group member nationwide. No one needs to suffer alone/in silence. There are others ready/willing to help prop up anyone in need of feeling stronger than their pain, needing to think/feel again that vital spark of thriving despite life’s challenges.

The landscape of pain that makes us vulnerable, is also the landscape peopled with support to help us feel strong again. Strong enough to say: “Still here!” with a tone of gratitude.

I know there are some members of our Group who do not have access to email. If you know someone in that category, share a printout of the weekly mass email with them. Call or text them with the topic of the week, inviting a discussion. It’s one way to help others remember that they are “still here”, part of this most wonderful tribe. In these uncertain times, having a tribe to call one’s own can make all the difference between surviving and thriving.

Measureless thanks, again, for the many prayers/blessings/contacts through this long ordeal of pain-filled challenges. Know that I love/appreciate each/every one of you!

Gentle hugs/much love,

Marian

12/31/2021 – Friday Morning Inspiration – Marian Griffey

Hello, everyone ~

Happy New Year, and apologies for the lack of a mass email last week. As some if not most of you know by now, I had been hospitalized from Wednesday morning until Friday evening. Ruptured L-2 on Wednesday morning; previously ruptured T-3, 4 (between the second week of September and Wednesday morning of last week). While there, x-rays/CT scan/MRI … hiatal hernia/tear in esophagus repaired. Bed rest/liquid diet from Wednesday forward, including now and likely into the New Year … because, the left hip is non-weight bearing (fractured? insulted? by the efforts to exit the hospital bed/get dressed/walk for the first time since the Wednesday morning incident; just the natural progression of osteoporosis? all the above?) 

Measureless thanks to The Family for getting the word out about that little adventure. More thanks to all who texted/emailed offering prayers and/or assistance with anything. I have been sustained by that outpouring of care/caring.

Needless to say, this has created yet another layer of challenges in our household. No two hours in any given day are similar or predictable. Husband has been great to help when possible; dealing “good enough” with the shock of being the one taking care of home chores/cats/wife as well as his own needs. Some moments are tough to get through (for both of us); some rather miraculous moments bring things back to a point of balance.

Meanwhile, my current status remains bed-bound while bones heal as much as is possible. With the anesthesia events finally dissipating, I can again resume reading/writing. Yeah!  My current book of choice is “Finding Beauty in a Broken World”, by Terry Tempest Williams. My holiday “gift” to you is the following excerpts:

– “… the cosmos works by harmony of tensions …

– We create the future through a rearrangement of forms, what we have learned from the past.

 – When you change your life, you also change your ideas.- The degree of our awareness is the degree of our aliveness.

– The gift I have been given has been in the waiting and in the natural passage of time.

– There are long skeins of time when I feel so confused and lost in the broken world of our own making. I don’t know who we have become or what to believe or whom to trust. … Our bodies remember wholeness in the midst of fragmentation.

– [in telling stories] Fear was transformed into comfort, curiosity melted into love, and the silence was no longer uncomfortable.”

Instead of one last neuron-stretching challenge for you in this fading year, I offer you a few quotes that show how others through the ages got their neurons stretched by Life and thus arrived at these profound conclusions below:

“So the unwanting soul 

sees what’s hidden,

and the ever-wanting soul

sees only what it wants.

Mystery of all mysteries 

the door to the hidden.”                               

Tao Te Ching

“The faith, and the love, and the hope are all in the waiting.”           

T.S. Elliott

“The world is too dangerous for anything but truth and too small for anything but love.”     

William Coffin
So, that’s the “short” version of what has felt like a very LONG series of painful, difficult challenges/partial recoveries and multiple set-backs/ the sum of 67 years on this Earth. Today is Day 6 of my 68th year of Life — a mere blip in the scheme of things; a mere drop in the ocean of human history; but what is an ocean but countless drops, eh? Each drop is part of the whole. Thanks for being part of mystery/magic.

Let’s keep the waves of  this “ocean Tribe” going!

Here’s hoping our private/collective New Year will unfold with healing/resolution/ peace/love/kindness. Take what is broken, dearly beloved, and make something whole! 

whole: (Latin) healthy, healing, healed; wholesome; holy

Gentle hugs/much love,

Marian

Friday Morning Inspiration – Marian Griffey

Good morning, everyone ~

Wow! Sixty-five degrees at 2:25a.m. on the 17th day of December!  or ? Or is this just another “is” in a long list of things we need to adjust to? 

Speaking of adjustments, the process of adjusting to changes/challenges can be made a little easier by developing a flow chart — either starting with the challenge and working forward to the present, or starting with the present and working backwards to the source. For example: Working backwards to the source of my current back-pain challenge, my flow chart looks something like this —

Age-related mild osteoporosis. Thus, bones shift, pulling muscles/tendons/ligaments into abnormal alignment; which pinches a wide range of nerves, producing pain. NOTE: this is a normal reaction to the abnormal development (yet, osteoporosis is a natural and normal part of aging; more so for some than others. 

A normal reaction to a normal condition.

Congenital cardiomyopathy. The condition has been well-tolerated up until recently. Throughout life, it has impeded my ability to do strenuous exercises/sports, and has on rare occasion caused spontaneous fainting. My inheritance of this condition is biologically normal. Just as is the inheritance of eye color and other traits passed along the DNA chain of command. 

congenital cardiomyopathy + age-related osteoporosis

= physical pain, decreased stamina/energy

All of which is NORMAL. My lab tests/physical exams/etc. show that I am within normal limits of organ functions — normal, despite the age-related decrease in bone density/muscle placement/nerve compression … and those three areas are reacting in a NORMAL fashion to the challenges being put upon them by the NORMAL progression of living day-to-day.

What we often fail to realize is that seemingly convoluted meaning of “normal”. If you get cut/scratched, it is NORMAL for your body to bleed. If you suffer with a congenital condition of hemophilia, the NORMAL reaction to the injury would be that you don’t stop bleeding. What is normal for each of us depends on that flow chart of how our DNA expresses itself/makes “me” ME. With all the myriad things that others label as “wrong; defect; flaw; problem…”. 

My “normal” is not your “normal”. Nor should it be; otherwise, we might as well be cloned or be robots. 

Where we fail ourselves and others, and where the medical community has been hijacked by the Business Model lies in the misinterpretation of words/terms/phrases/diagnoses.

What we want NORMAL to be is “perfect; no flaws; no challenges; no mistakes; no degeneration or restriction”. When did NORMAL life ever unfold without challenges/adjustments/individuality/uniqueness? 

It is NORMAL for me (and only me, because no one else is exactly like me) to avoid strenuous exercise, due to the limited ability of my heart to work perfectly all the time. Challenge me to a foot-race and you’ve wasted both your and my time/energy. If a bear starts chasing us, you have my permission to leave me at the “bait”. Save yourself!  You have my permission to run forth-n-prosper!

It is NORMAL for me to faint if I try to push my body beyond its ability. It is NORMAL for my muscles to change position as osteoporosis decreases my ability to maintain proper posture. It is NORMAL for nerves to be pinched by muscles that shift/cramp/spasm. 

This is my normal life, folks! I’m in the process of adjusting to all the challenges that my Life Path has brought me to.  I have not conquered nor fully resolved any of them, for that is an end-of-life achievement. Growing old is a privilege. It’s not for sissies, and believe me when I say that I’m not now nor ever have been a “delicate flower” at any age. I cannot fight against the NORMALs that Life has given me to face. I can, however, learn how to better adjust to all the NORMALs that are inevitable.

After three months of dealing with back-pain on an almost continuous basis, I’m happy to report measurable progress in my recovery plan!  Until this past week, I had been “living” primarily in my recliner, only venturing forth on the pain-filled journey to the bathroom and back again. Some of those journeys were merely taxing; some were horrors. “Down time” allows much opportunity for thinking (“cogitating” as my dad would say). Knowing that I have adverse reactions to manufactured steroids, I wondered if perhaps too I could be ultra-sensitive to my own adrenaline/stress hormones (natural steroids). To test my hypothesis, I took a single capsule of 25mg Benadryl, and paid attention to the results. 

Yes!  By reducing the allergic reaction to my natural (normal) steroids, inflammation decreased and my mood/internal dialogue improved. By charting my own flow-chart of how I got from There to Here, I could see more clearly how to better manage my physical/emotional/mental/spiritual pain. My recent blood-panel results are proof that my self-care regimen is working. 

I am again able to sit upright at my desk with very little pain/discomfort, and only intermittent bouts of muscle spasm/cramping. (They are trying to remember their job, bless ’em!) Not for long periods, of course, for muscles have grown weaker from lack of exercise, and cannot adjust to their new positions/textures. Measurable progress, however, remains a blessing! Hallelujah! 

Not yet able to pull those 10-hour days of steady work/activity. Those days may be and likely are behind me. If so, I will adjust. Just for now, it is “good enough” to sit at my desk sometimes … to sleep more often in my own bed and only sometimes in my recliner … to do some gentle Yoga stretches and carry on a conversation without being interrupted by yelps of spontaneous pain. 

Thank you all for those continuous prayers and many offers of help/support! Better than Benadryl!  

Let’s continue that brand of “good medicine” regimen for one another! Not just praying for one another but letting one another know that prayers are being said. Otherwise, it’s very LONE-n-lonely day-to-day we’re living. 

Also, thank you for the prayers for my husband during this difficult time. Poor lamb, he has had his adjustments to make too. 

Another bit of good news to share — we have a new member in our Group. Her name is Susan; she lives in Orlando; she suffers with chronic back pain and is recovering from a second surgery. She has asked that I share her email information with the Group in hope of generating a support network as she faces her personal list of “things to adjust to”. Being so far away, and being in chronic pain, it is nearly impossible for her to attend any of our in-person meetings. Emails know no borders or geographic boundaries and are a way of helping us feel NOT ALONE in the world. I have been in email contact with Susan and have enjoyed one phone session with her thus far. If you feel inclined to get acquainted, here is her contact info:

susanhavill@yahoo.com

Which brings up another thing to ponder: “virtual Group sessions”. Who is in favor of this? I am a dinosaur when it involves anything electronic; however, I’m willing to get “baptized” into that congregation (only in the shallow part of the pool, LOL). I know nothing in this particular realm. If someone else is willing to be our i.t. coordinator, that would be fabulous! I do realize that with chronic pain, we can seldom plan in advance, never knowing what any day or hour will hold in store. Just let me know your thoughts/feelings on the matter. Thank you!

In regard to in-person meetings, after the New Year I hope we can resume those. Let me know, please-n-thanks, what is the best day/time for your personal schedule, in regard to a weekly small-group meeting. I will focus on the majority agreement for this. It may be that we hold two small-group meetings — one for the vaccinated and one for the non-vaccinated. (Regardless of personal beliefs/choices, persons in pain remain deserving of pain-management support-group meetings.) SenCen Programs Manager, Nick Hauser, has generously agreed to put our meetings back on the calendar whenever I am ready to do so. We could, for instance, offer a 2-hour session for the non-vaccinated, followed by the remainder of the afternoon being reserved for the vaccinated. I am open for suggestions/ideas about this.

I hope to be able to host small-group sessions here in my home as we have done in the past. Also, to resume private sessions after the New Year. There is no crystal ball that can guarantee anything, of course. Adjustment is like a river — you can never step into the same water twice; and, what is expected usually turns out to be a surprise. (How grateful I am that Life is full of surprises … never boring … flowing forward.) 

Thus far, this week’s mass email has been about GRATITUDE. That adage from my younger (somewhat hippie) days remains a timeless truth: Attitude of Gratitude will get us through much! The word comes to us from the Greek, from the root word “grace”. It’s the “amen” we whisper at the end of our private list of gratitude for such things as food on the table, shoes on our feet, ability to survive some rather dire situations/painful consequences. It is the Spirit of our major holidays, minor celebrations, milestones and baby-steps. It is the secret of how we can step into our right-brain whenever the left-brain is overwhelmed by life’s challenges, brain-file cascade events, fresh shocks, compassion fatigue, simple or complex fears, pain on every level of our being.

We have gratitude. We can take it one step further: cultivate an attitude of gratitude. We just cannot live perpetually/indefinitely in that state of being. Not even the saints throughout history could do so; and there have been those who tried.

No growth without challenges! Our brains need multitudes of varied experiences. Our minds need growth that yields deeper compassion, increased understanding. We need a few challenges along the way! Some big, some small, some mysterious and others so simple we tend to overlook them. The past few years … well, that’s another “dead horse” that does not bear repeating nor beating; yet, even this depth of long-term challenge-of-challenges has taught us much!

The next time you look at yourself in a mirror, tell yourself: “Good job! Thank you!” Then, take note of what else your right-brain observes. We can step into our right-brain realm a thousand-thousand times a day. But, we also need to deal with the left-brain challenges, knowing that we will eventually have something else to tell our reflection, some other “good job” that increases our sense of grace/gratitude. 

As the hours pass and bring a slowly rising level of unseasonal warmth into our shared Friday, may our personal/collective mantra for the week ahead be: “Love, Peace, Kindness”. These three attitudes, to increase our gratitude and to bless ourselves as well as others ~ ’tis the season, eh?

Gentle hugs/much love,

Marian

Friday Morning Inspiration – Marian Griffey – ACPA Facilitator

Good morning, everyone ~

Apologies for getting this out later than usual. My days/nights have been mixed up for several weeks now, and the calendar in my head doesn’t always match the one on the wall. 😯

It has been a rough experience; sometimes more so than others. For weeks now, I’ve been sleeping in my recliner, unable to get into/out of bed without causing severe pain. Then, as the pain subsided, I thoroughly enjoyed sleeping in my own bed. The only problem: I slept from 7:00a.m. until 5:00 p.m.! 😯 For several days in a row! Which left me wide awake at night … sitting upright in my recliner … watching Netflix, catching up on history, documentaries, Sci-Fi, and favorite series.

If you have a Facebook account, you may want to check out the ACPA’s monthly newsletter. There are lots of helpful hints for how to manage various types of pain, especially during the holidays. As I myself get older and develop more physical challenges, I do less-n-less in every area of my life. This greatly disappoints me, even though I understand that this is a normal progression. My disappointment plays a major role in the level of pain my body suffers. That dual role can ooze outward, affecting others around me. Even the cats can sense when I am not at my perky best. Knowing this, my disappointment grows, for I don’t want to negatively affect those I love.

My sister, who is 13 years older than I, understands this all too well. As we email one another each day, we speak honestly about our disappointments. We are a safe place for one another to voice our honest feelings. We also list our blessings, which helps remind one another that it’s the blessings in our lives that bring perspective back into balance. Yes, we are genuinely disappointed; and, yes, we are blessed! The point of balance is halfway between the two extremes.

Several dear friends and I have developed a similar method of pain management. By having a safe place and being a safe place for others to express true feelings is a priceless partnership … and one of the leading blessings in anyone’s life. Most of us have been through the harsh experience of being rebuffed, disbelieved, lectured, or ignored when we’ve attempted to find that safe place in family/friends/loved ones, even in trusted clergy or medical professionals. That adds a sense of betrayal to our list of disappointments.

Don’t give up the search! There’s a “safe place” person somewhere! Remember that adage: “You have to kiss a lot of frogs to find a prince.” Finding a person with whom you can share your personal truths may take a few frog-kisses. Knowing who you CAN trust to and who knows they CAN trust you is a priceless “magic potion” in our pain-management toolbox.

If you have that sort of safe-place person in your life, let them know what a blessing they are in your life. it could be the best Christmas gift they get in this challenging season/uncertain world. If you don’t have one, grab hold of your courage and reach out one more time in your search to find such a person. Discover just how courageous you are in the face of pain/disappointment/betrayal and celebrate the blessing of that courage.

In these uncertain times, let’s make a list of what we are certain about … and let’s start with naming those safe-place people in our lives, and those for whom we ourselves are a safe place.

Know that each of your names is on my list! 🤗😍😊🎉 Know that I cherish each of you and am measurelessly grateful for being part of such a “medicinal” tribe!

Gentle hugs/much love,

Marian

Endogenous opioids contribute to the feeling of pain relief in humans – PAIN

https://journals.lww.com/pain/Fulltext/2021/12000/Endogenous_opioids_contribute_to_the_feeling_of.5.aspx

RESEARCH PAPER

Endogenous opioids contribute to the feeling of pain relief in humans

Sirucek, Lauraa,b,c,*; Price, Rebecca Christined,e; Gandhi, Wiebkee,f,g; Hoeppli, Marie-Eved,e,h; Fahey, Emmae; Qu, Anniee; Becker, Susannea,b,c,e,i; Schweinhardt, Petraa,b,c,d,e,fAuthor InformationPAIN: December 2021 – Volume 162 – Issue 12 – p 2821-2831doi: 10.1097/j.pain.0000000000002285


Endogenous opioids mediate the pleasurable responses to positively reinforcing stimuli such as palatable food. Yet, the reduction or omission of a negative experience can also be rewarding (negative reinforcement). As such, pain relief leads to negative reinforcement and evokes a pleasant feeling in humans. Although it has been shown that the feeling of pleasure associated with positive reinforcement is at least partly mediated through endogenous opioids, it is currently unknown whether similar neurochemical mechanisms are involved in the pleasant feeling evoked by pain relief. In this study, 27 healthy participants completed 2 identical experimental sessions, 1 with placebo and 1 with naltrexone, an endogenous opioid antagonist. Pain relief was induced by superficial cooling after heat stimulation of capsaicin-sensitized skin. Participants rated the relief and pleasantness in response to the cooling. Endogenous opioid blockade by naltrexone decreased relief and pleasantness ratings compared with placebo (P = 0.0027). This study provides evidence that endogenous opioids play a role in mediating the pleasant feeling of pain relief in humans. Clinically, the rewarding nature of pain relief and its underlying mechanisms require consideration because of their potential reinforcing effects on behaviors that might be beneficial short-term but maladaptive long-term.

1. Introduction

Endogenous opioids are involved in a multitude of physiological and psychological processes, including an important role in mediating analgesia and pleasure associated with reward [annually reviewed in the “Endogenous Opiates and Behavior” series12]. The link between reward-associated pleasure and endogenous opioids is supported by animal studies implementing food or sucrose as the rewarding stimulus leading to positive reinforcement of hedonic “liking” reactions.15,50 In humans, also the feeling of pleasure in response to positively reinforcing stimuli such as food intake has been shown to involve endogenous opioids signaling.16,57 In addition to positively reinforcing stimuli, the reduction or omission of an aversive experience, such as pain, can be rewarding, leading to negatively reinforced behavior. Negative reinforcement associated with pain relief has consistently been shown in conditioned place preference paradigms, with rodents favoring locations not previously paired with painful stimuli over those previously paired.26,38,39 Thus, pain relief seems to have rewarding properties.

In line with the notion that pain relief is rewarding, negative reinforcement might be associated with a similar feeling as positive reinforcement, ie, pleasure. For example, attenuation of experimental pain in healthy volunteers leads to the feeling of pleasure in addition to reduced perceived pain intensity.29 In rodents, negative reinforcement produced by pain relief has been demonstrated to require supraspinal endogenous opioid signaling,39 similarly to positive reinforcement. Whether the feeling of pleasure associated with pain relief also depends on endogenous opioid action, however, remains an open question. Therefore, it was tested in this study whether the feeling of pleasure associated with pain relief is mediated by endogenous opioids in healthy humans. Pain relief was achieved by the application of cool stimuli after heat stimulation of capsaicin-sensitized skin, similar to Mohr et al.36 and Leknes et al.,29 and the effect of the opioid-receptor antagonist naltrexone on participants’ ratings of relief and pleasantness was assessed using a randomized, placebo-controlled, double-blind, counterbalanced, crossover study design. It was hypothesized that blocking endogenous opioids with naltrexone, a potent μ-receptor antagonist,54 decreases subjective relief and pleasantness ratings compared with the placebo condition. Because endogenous opioid blockade can increase perceived pain intensity,2 which in turn has been shown to influence the magnitude of pain relief,29 this study used perception-adjusted, rather than temperature-adjusted, painful heat stimulations and analyzed naltrexone effects on pain sensitivity. Furthermore, because pleasure depends on the internal state of an individual,14 the baseline emotional state of participants between the naltrexone and placebo condition was examined as additional potential confounding factor.

2. Methods

2.1. Participants

Healthy male and female volunteers between 18 and 35 years of age were recruited through advertisement on the internal McGill University web page. Exclusion criteria were any present or past pain condition, psychiatric disorders, substance abuse behaviors, alcohol consumption of more than 100 mL alcohol per week, tobacco use, regular night shifts, sleep disorders, or any medical conditions including neurological diseases. The study was approved by the McGill University Institutional Review Board in accordance with the Declaration of Helsinki (2013). Written informed consent was obtained from all participants before the start of the experiment.

A priori sample size calculation for a similar experimental design yielded a target sample size of 28 participants to detect a desired medium effect size of drug (ie, placebo vs naltrexone) in a 2-way (drug: 2 levels, stimulation type: 3 levels; in this study: 2 levels for all fixed factors) repeated-measures analysis of variance (ANOVA) design with a 5% probability to commit a type I error (α = 0.95) and a 20% probability to commit a type II error (β = 0.8).

For this study, the recruited sample comprised 31 participants. Four participants did not return for the second session, 2 due to nausea (both received naltrexone in the first session) and 2 for unknown reasons. This resulted in a final sample of 27 participants (mean age ± SD 21.70 ± 2.77 years, 14 women). Of this final sample, 3 did not complete the trials at the higher target pain intensity because the temperature safety cutoff (46°C) was exceeded during the calibration procedure. Of these 3 participants, one also reached the temperature safety cutoff during the “self-adjustment phase” in 1 trial at the target pain intensity “170”. Because the applied statistical methods (ie, general linear mixed models [GLMMs]) account for missing datapoints, these participants were still included in the analyses.

2.2. General study design

Participants completed 2 identical experimental sessions, 1 with placebo and 1 with naltrexone following a randomized, placebo-controlled, double-blind, counterbalanced, crossover study design. Superficial cooling after heat stimulation of capsaicin-sensitized skin was used to induce pain relief. A timeline of the experimental sessions is shown in Figure 1A.

Figure 1.
Figure 1.: Study design. (A) Timeline of 1 experimental session. (B) Overview of 1 trial. HPT, heat pain threshold; HTT, heat tolerance threshold; HRV, heart rate variability; PCS, Pain Catastrophizing Scale; POMS-Bi, Profile of Mood States Bipolar Scale; SCR, skin conductance response; TEPS, Temporal Experience of Pleasure Scale.

Participants were seated upright throughout the whole session. Before placebo/naltrexone administration, participants filled in the Profile of Mood States Bipolar Scale (POMS-Bi)32 and a naltrexone side-effect survey. Resting heart rate was recorded for 5 minutes. Subsequently, the participants received 1 of 2 identically looking capsules that was administered orally, containing either placebo (microcrystalline cellulose powder) or naltrexone (both at 1 mg/kg body weight). The order of placebo or naltrexone session was randomized and counterbalanced across participants. Testing started 1 hour after placebo or naltrexone administration to correspond with the peak blood concentration of naltrexone.21 Immediately after placebo or naltrexone administration in the first session, participants completed the Pain Catastrophizing Scale (PCS)52 and Temporal Experience of Pleasure Scale (TEPS).20 Subsequently, heat pain and heat tolerance thresholds were determined in the testing area (ie, volar forearm) using the method of limits19 to assess whether early naltrexone effects on pain sensitivity occurred. During the remaining waiting period, participants could read or study quietly. A second side-effect survey was performed 35 minutes after placebo/naltrexone administration. One hour after placebo/naltrexone administration, participants completed calibration procedures to determine the individual target temperatures followed by the trials to induce pain and pain relief (at 2 different target pain intensities, 4 trials each, resulting in 8 trials in total) as described in detail in section “Thermal testing procedures”. Skin conductance was recorded during pain and pain relief at both target pain intensities. After the last trial, participants filled in a second POMS-Bi and a third naltrexone side-effect survey. In addition, an exit interview was performed assessing the blinding of participants and the experimenter. The experimental sessions lasted approximately 1.5 hours each, with testing occurring between minutes 60 and 90 (half-life of naltrexone: 3.5 hours21).

2.3. Thermal testing procedures

Capsaicin was applied topically 40 minutes after placebo/naltrexone administration on a 3 × 3-cm2 skin area on the nondominant volar forearm 3 cm below the elbow crease using a cream with 0.4% capsaicin, prepared by a compound pharmacy. After 20 minutes, the cream was removed and thermal stimuli were delivered to the sensitized skin area with a 3 × 3-cm2 thermode (Pathway, Medoc, Israel) to evoke painful hot and relieving/pleasant cooling sensations. The thermode was fixed to the forearm with a Velcro strip. Before testing, participants were instructed regarding all thermal testing procedures. During thermal testing, participants provided ratings on computerized rating scales or controlled the thermode temperature using a computer mouse. Right mouse button presses increased ratings/temperature (by 0.1°C), and left mouse button presses decreased ratings/temperature (by 0.1°C). Short instructions and visual feedback were provided on a computer screen throughout the thermal testing (Fig. 1B).

2.3.1. Rating scales

Pain intensity was rated on a horizontal visual analogue scale (VAS) ranging from 0 “no sensation” (left end of the scale) to 200 “most intense pain tolerable” (right end of the scale) with 100 being the pain threshold. Unpleasantness ratings were provided on a VAS ranging from 0 “neutral” to 100 “extremely unpleasant”. Relief was rated on a VAS ranging from “no relief” to “intense relief”, and the instructions displayed on the computer screen were “press to rate any relief you feel”. The pleasantness VAS ranged from “neutral” to “extremely pleasant”, and the instructions displayed on the computer screen were “press to rate how pleasant your sensation feels”. Because the construct “relief” has rarely been used in human perceptual studies, participants were instructed before testing that relief is considered akin to the sensation of putting something cool on sunburned skin or taking a cool shower on a hot day. The experimenter avoided associating words such as “pleasant”, “better”, or “good” with relief.

2.3.2. Experimental trials

Trials were performed using 2 target pain intensities: “170” and “195”. In each session, all trials at “170” were performed before the trials at “195” to reduce sensitization effects. Immediately before the first trial of each target pain intensity, individual temperatures for the respective target pain intensity were determined with the following calibration procedure: The thermode temperature started at 32°C and increased at a rate of 1°C/s. Participants were asked to constantly rate their perceived intensity on the computerized intensity rating scale using the computer mouse. When participants reached the intensities of “170” and “195”, the computer adjusted the temperature during 60 seconds for “170” and during 30 seconds for “195”, so that the rated intensity stayed constant at “170” or “195” by decreasing the temperature of the thermode if ratings were above the target pain intensity or increasing if ratings were below the target pain intensity. The duration for the target pain intensity of “195” was shorter compared with “170” to decrease the likelihood of participants not tolerating the entire length of the stimulation. The resulting average temperatures for the 2 target pain intensities of “170” and “195” were used as the starting temperatures for all trials of the participant at the respective target pain intensity.

Each trial consisted of 2 phases starting directly after calibration: (1) a painful phase (heating) followed by (2) an outcome phase (cooling). Between the painful and the outcome phase, participants completed a short (5 seconds) motivation task with the thermode temperature remaining at the level of the painful phase. Briefly, participants had to press a mouse button as often as they could while a visual cue was presented on the screen. The motivation task was not part of the present research question and will therefore not be discussed further; important for the current study is that it was identical between the placebo and the naltrexone sessions. Four trials were performed at each target pain intensity (ie, “170” and “195”), resulting in 8 trials in total. An overview of 1 trial is depicted in Figure 1B.

2.3.2.1. Painful phase

The thermode temperature increased from baseline (32°C, rate 1°C/s) to the predetermined individual target temperature for the respective target pain intensity (ie, “170” or “195”). During this ramp, participants were presented with a fixation cross on the computer screen. After reaching the target temperature, the painful phase comprised 3 intervals. First, participants were instructed to control the thermode temperature using the computer mouse to maintain a constant perceived pain intensity, ie, “170” or “195”, for 1 minute or 30 seconds, respectively (“self-adjustment phase”). Second, immediately after the “self-adjustment phase”, participants were asked to rate the unpleasantness of the perceived pain. The unpleasantness rating scale was displayed for 8 seconds. Subsequently, participants were asked to rate the overall pain intensity (0-200) they had perceived during the “self-adjustment phase”. This served as manipulation check if participants had managed to maintain the respective target pain intensity (ie, “170” or “195”). The intensity rating scale was displayed for 8 seconds.

2.3.2.2. Outcome phase

After the painful phase, the thermode temperature decreased to 25°C. The temperature of 25°C was determined to be perceived as nonpainful and pleasant after the same heat-capsaicin stimulation in pilot experiments. During the decrease, a fixation cross was shown on the screen. When the thermode had cooled down to 25°C, the participants were asked to continuously rate the perceived relief in 2 of the 4 trials with the 2 pain intensities (“outcome relief”) and perceived pleasantness in the other 2 trials (“outcome pleasantness”). The cooling stimulus was applied for 15 seconds. The order of trials with the “outcome relief” and the “outcome pleasantness” was counterbalanced across participants.

2.4. Autonomic responses

Heart rate and skin conductance were obtained to calculate heart rate variability (HRV) and skin conductance responses (SCR). Heart rate variability can be used to examine the autonomic control of the heart22 and was used here as a physiological measure of the participants’ emotional responding.3 Skin conductance responses served as measure of physiological responses to painful or relieving thermal stimuli.30,48 Heart rate and skin conductance were recorded using a Biopac MP150 system (Biopac Systems Inc, Goleta, CA).

Electrocardiograms were measured at rest at the beginning of each session with surface electrodes (type EL503, Biopac Systems Inc, Goleta, CA) for 5 minutes (sampling frequency 1000 Hz). Data were visually inspected, and any artifacts were manually removed. Heart rate variability was calculated from heart rate data through power spectral density analysis using the AcqKnowledge software (Biopac Systems Inc, Goleta, CA) recommended settings. The ratio of low-frequency to high-frequency (LF/HF) components were assessed which is used as index of sympathovagal balance, ie, the balance between the sympathetic and parasympathetic autonomic nervous system.53

Skin conductance was recorded during the painful phase and the—relieving—outcome phase at both target pain intensities. Surface electrodes (type EL507, Biopac Systems Inc, Goleta, CA) were placed at the distal phalanx of the index and middle fingers of the participant’s nondominant hand. Skin conductance was sampled at 1000 Hz and high-pass filtered (0.05 Hz). Using Ledalab 3.4.9,10 integrated SCRs (ie, area under the curve) were calculated of identified SCRs (amplitude threshold: 0.01 µS) in the extracted phasic driver between the first 1 to 7 seconds after the onsets of the painful phase and the outcome phase, respectively. Compared with SCR amplitudes, the integration of SCRs reduces bias because of the superposition of SCRs and takes into account their continuous nature.10

2.5. Questionnaires

Psychological factors are known to influence pain perception43,56 and, conceivably, might affect pain relief. To assess the influence of psychological factors, self-report measures were included in this study, specifically the POMS-Bi, the PCS, and the TEPS.

The POMS-Bi was used to evaluate possible naltrexone effects on participants’ mood and the participants’ mood on the 2 testing days. The POMS-Bi assesses positive and negative affective states, rated on a 4-point rating scale ranging from “much unlike this” to “much like this” (score range: −36 to 252; −36 meaning max. negative affect, 252 max. positive affect, and 108 a balanced negative-positive affect). The total POMS-Bi score and the 2 subscores POMS-Bi “composed-anxious” (score range: 42 to −6) and “elated-depressed” (score range: 42 to −6) were used for further analysis.

The PCS and the TEPS were completed by the participants during the first session immediately after placebo/naltrexone administration with the assumption that naltrexone did not yet exert pharmacodynamic effects. The PCS consists of 13 questions about past painful experiences, each rated with a score between 0 “not at all” to 4 “all the time” (score range: 0-52; 0 meaning no catastrophizing). The TEPS is a measure of the individual pleasure experience and includes 2 subscales for anticipatory (ie, pleasure of forthcoming positive events) and consummatory (ie, “in-the-moment” pleasure) pleasure. Eighteen questions (10 for anticipatory pleasure and 8 for consummatory pleasure) are rated on a 7-point rating scale ranging from 0 “very false for me” to 6 “very true for me” (score range: 0-108; 0 meaning no pleasure). The subscale for consummatory pleasure (score range: 0-54) was used for further analysis.

Potential side effects of placebo or naltrexone were assessed using a side-effect survey at different timepoints throughout each session (Fig. 1A). The side-effect survey included 7 items: “dry mouth”, “dry skin”, “blurred vision”, “tiredness”, “nausea”, “dizziness”, and “headache”. For each item, participants were asked to choose the best descriptor of how they felt at that moment on a 5-point rating scale ranging from 0 “none” to 4 “extremely strong” (score range: 0-28; 0 meaning no side effects). The sum of all side effects was calculated for each timepoint.

2.6. Exit interview

At the end of each session, the participants and the experimenter were asked whether they believed placebo or naltrexone had been administered in that session (possible answers: “placebo”, “drug”, or “I do not know”). After the second session, participants were additionally asked what they believed the purpose of the experiment was.

2.7. Data analysis

Statistical analyses were performed using R 3.6.1/RStudio 1.2.5001 for Mac. Statistical significance was set at α = 0.05.

2.7.1. Naltrexone effects

Naltrexone effects and between-session differences were analyzed using GLMMs (function lmer() from R package “lme4”). All models included at least drug (2 levels: placebo and naltrexone) and sex (2 levels: female and male) as independent variables. Sex was included in the model because sex differences are frequently reported in pain-related outcomes [reviewed in Ref. 18], which might also apply for pain relief. Participant identifier was included as a random effects factor. All independent variables were first entered into the model including interaction effects, except for sex, which was included as main effect only. If interactions were not significant, they were removed from the model. Because sex effects were not part of the main research question, sex was removed from the model if its effect was not significant. Model diagnostics (inspection of residual distribution, leverage, and DFBETA values) were used to check requirements for GLMMs. Unless reported otherwise, requirements were met. If potential influential observations were identified (datapoints exceeding a DFBETA value of 2/√n9), the final model was repeated without the respective datapoints (reported in the respective section). If removal of influential observations led to changes of the statistical inference, the model without the influential case is reported. Otherwise, the model with the full data set is reported. Effect sizes are not reported because there exists no agreement on how to calculate standard effect sizes for mixed model structures because of the way variance is partitioned.45 Nevertheless, GLMMs were used for their advantages in controlling for type I errors compared with alternative approaches, which make results from mixed models more likely to generalize to new observations.4

2.7.2. Naltrexone effects on relief/pleasantness

Relief/pleasantness ratings were translated into numerical ratings from 0 “no relief”/“neutral” to 100 “intense relief”/“extremely pleasant”. The maximum ratings of the 8 trials (4 trials at “170” and 4 trials at “195”) were averaged over the 2 trials ending with the same outcome phase, ie, relief or pleasantness, and used for further analysis. Target pain intensity (2 levels: “170” and “195”) and outcome (2 levels: relief and pleasantness) were additionally included as independent variables in the GLMM.

2.7.3. Potential confounders

Endogenous opioid antagonists might have potentially confounding effects on the main outcomes of relief/pleasantness ratings, eg, by influencing pain sensitivity.42 Pain relief might further be influenced by participants’ mood.31 To investigate such potentially confounding effects, the following exploratory analyses were performed.

2.7.3.1. Naltrexone effect on pain sensitivity

The temperatures as well as the unpleasantness and pain intensity ratings of the painful phase were examined for naltrexone effects. For temperature, the average during the “self-adjustment phase” was used. Target pain intensity (2 levels: “170” and “195”) and outcome (2 levels: relief and pleasantness) were included as additional independent variables in the GLMMs.

Furthermore, naltrexone effects on SCRs, as a measure of physiological responses to painful or relieving thermal stimuli,30,48 were examined. Integrated SCRs were log10 (x + 1)-transformed to meet requirements for GLMMs. The additional independent variables target pain intensity (2 levels: “170” and “195”), phase (2 levels: painful phase and outcome phase), and outcome (2 levels: relief and pleasantness) were included in the GLMM.

2.7.3.2. Participants’ mood

It was first analyzed whether naltrexone influenced participants’ mood over the course of the sessions. Timepoint (2 levels: start of session and end of session) was included as additional independent variable in the GLMM. Each POMS-Bi score (“composed-anxious” subscore, “elated-depressed” subscore, and total score) was examined for a drug x timepoint interaction effect in a separate GLMM.

Second, potential between-session differences of the participants’ emotional state at baseline (ie, start of the session) were examined. General linear mixed models were used to compare each POMS-Bi score (“composed-anxious” subscore, “elated-depressed” subscore, and total score at start of the session) between sessions, as well as the baseline resting HRV LF/HF component, here used as a physiological measure of participants’ emotional responding.3

2.8. Pain relief: exploring interindividual differences

Correlations with questionnaire scores were performed using Spearman’s rho because questionnaire scores are based on an ordinal level of measurement. For all other correlational analyses, data were assessed for normality through visual inspection of histograms and QQ-plots. Pearson’s r was used for correlations of normally distributed data, and Spearman’s rho was used for non-normally distributed data.

2.9.1. Association with psychological factors

Taking an exploratory approach, it was investigated whether (1) the magnitude of perceived relief/pleasantness is associated with pain catastrophizing or consummatory experience of pleasure and (2) naltrexone effects on relief/pleasantness are associated with these 2 psychological factors.

For (1), Spearman’s rho was calculated between maximal relief/pleasantness ratings in the placebo session at both target pain intensities (ie,“170” and “195”) and PCS as well as TEPS consummatory scores.

For (2), Spearman’s rho was calculated between the differences in maximal relief/pleasantness ratings between the naltrexone and placebo session (ie, naltrexone relief/pleasantness ratings—placebo relief/pleasantness ratings, further referred to as “delta NX-PL”) at both target pain intensities (ie,“170” and “195”) and PCS as well as TEPS consummatory scores.

2.9.2. Interindividual variability

Because of the observed high interindividual variability of relief/pleasantness ratings, an additional exploratory analysis was performed. Before investigating interindividual differences in rating behavior of relief/pleasantness, the intraindividual stability of participants’ relief/pleasantness ratings in the placebo session was examined using a single-measurement, absolute-agreement, 2-way mixed-effect intraclass correlation coefficient analysis.35 Because the relief ratings were not different from the pleasantness ratings, nor between the trials at target pain intensity “170” and the trials at “195”, all 8 trials were included in the analysis. To gain insight into observed interindividual differences in relief/pleasantness ratings, it was investigated whether there was an association between how much relief/pleasantness the participants reported in the placebo session and the magnitude of naltrexone effects on these relief/pleasantness ratings. Maximal relief/pleasantness ratings in the placebo session at both target pain intensities (ie,“170” and “195”) were correlated with the respective delta NX-PL (Spearman’s rho). Because a random string A (here: relief/pleasantness ratings in the placebo session) will typically correlate with a random string B-A (here: the respective delta NX-PL), the following statistical analysis was performed to dissociate the observed correlation effects from effects occurring by the flaw A ∼ B-A: 10’000 random samples with the same sample size as in this study (N = 27) were created using the same mean values and SDs of the relief and pleasantness ratings (at “170” and “195”) of the naltrexone and placebo session, respectively. To account for the inherent correlation of within-subject ratings, the strength of correlations between the random sample A (ie, random relief/pleasantness ratings in the placebo session) and the random sample B (ie, random relief/pleasantness ratings in the naltrexone session) was adjusted to reflect the respective correlations observed in this study. Differences between the random naltrexone and placebo ratings (ie, random delta NX-PL) were calculated and correlated to the random ratings in the placebo session. The resulting distribution of the 10′000 random correlation coefficients represents what could be expected in 10′000 random samples, given the flaw A ∼ B-A and an inherent correlation of A and B. From this distribution, the mean, the 97.5% quantile and the 0.25% quantile were calculated. If the observed correlation coefficients fall within the limits of the 0.25% and the 97.5% quantiles of the random distribution, the observed effects are deemed not to be different from an effect expected, given the flaw of A ∼ B-A and an inherent correlation of A and B. If the observed correlation coefficients are outside of the limits of the 0.25% and the 97.5% quantiles of the random distribution, the observed effects are deemed to be different from an effect expected by the flaw of A ∼ B-A and an inherent correlation of A and B. with the probability of 5% to commit a type I error.

2.9. Side effects and exit interview

Side effects were compared between placebo and naltrexone sessions for each timepoint using the difference to before placebo/naltrexone administration, with Pratt signed-rank tests (an alternative for Wilcoxon signed-rank tests accounting for ties41). To assess whether participants and/or experimenter could distinguish placebo and naltrexone sessions better than by chance, a chi-square goodness-of-fit analysis of correct and incorrect responses of the exit interview was performed. If participants or experimenters reported “I do not know”, it was assumed that placebo/drug administration could not be distinguished and the answer was excluded from further analysis. “Placebo”/“drug” answers were categorized into correct and incorrect responses and compared with the expected frequency of 0.5 (corresponding to a 50% chance of correct guessing). Two chi-square goodness-of-fit analyses were performed: 1 for participant responses and 1 for experimenter responses. The exit interviews about the experiment’s purpose were assessed qualitatively.

2.10. Bayesian analysis of null effects

Several null effects (ie, no statistically significant differences) were observed. Because any null effect of the tests used here (GLMMs, correlation analyses, and Pratt signed-rank tests) only indicates that the null hypothesis (H0) cannot be rejected, Bayesian factors were calculated to assess the strength of the evidence for H0.24 Bayes factors are usually expressed as the ratio of the likelihood of the alternate hypothesis (H1) to the likelihood of H0 (BF10). A value for BF10 between 1 and 3 is considered anecdotal (ie, weak) evidence for H1, while a value between 3 and 10 suggests moderate evidence for H1. BF10 values between 1 and 0.33 represent anecdotal evidence for H0, and values between 0.33 and 0.1 are considered moderate evidence for H0.24,28

Bayes factors were calculated for all detected null effects. This was deemed particularly important to reduce the likelihood that the main results were influenced by potential confounding factors, foremost different pain sensitivities across sessions.

Bayes factor analysis was performed in R 3.6.1/RStudio 1.2.5001 for Mac using the “BayesFactor” package except for the nonparametric analysis of side effects, which was performed using Jeffreys’s Amazing Statistics Program 0.14.0.0. Because the Pratt signed-rank test is unavailable for Bayes factor analysis, a Bayesian Wilcoxon signed-rank test was performed (which, in the conventional analysis confirmed the result of the Pratt signed-rank test). Priors on the effect were specified as Jeffreys-Zellner-Siow priors5,46 for all ANOVA designs (ie, GLMMs), as shifted, scaled beta priors34 for all correlational designs, and as zero-centered Cauchy priors24 for the Bayesian Wilcoxon signed-rank test. Results from analyses with standard medium-width priors (ie, r = 0.71 for ANOVA designs and Bayesian Wilcoxon signed-rank test, r = 0.33 for correlational designs) were used for interpretation (Figures, Supplemental Digital Contents 1 and 2, for details and results for different prior widths, available at https://links.lww.com/PAIN/B355).

3. Results

3.1. Naltrexone decreases relief/pleasantness ratings

Naltrexone intake resulted in reduced relief (mean ± SD at “170”: 54.6 ± 21.6, “195”: 55.8 ± 23.7) and pleasantness ratings (“170”: 58.7 ± 21.2, “195”: 53.8 ± 26.3) compared with placebo (relief “170”: 61.8 ± 21.4, “195”: 64.9 ± 24.6; pleasantness “170”: 63.1 ± 25.0, “195”: 63.5 ± 24.8) at both target pain intensities (F[1177.5] = 9.29, P = 0.0027; Fig. 2A). The target pain intensity had no effect on relief or pleasantness ratings (F[1178.4] = 0.0046, P = 0.95), and relief and pleasantness ratings did not differ from each other (F[1177.2] = 0.034, P = 0.85). Neither interaction effects nor the effect of sex was significant and therefore removed from the model. In the final model, 14 potential influential observations (of 207) were identified. Removal of the respective datapoints did not change the statistical inference of the model.

Figure 2.
Figure 2.: Naltrexone reduces relief/pleasantness ratings. Naltrexone effect on relief/pleasantness ratings at target pain intensities “170” and “195” displayed as raw values in the naltrexone and placebo session (A) and as difference in relief/pleasantness ratings between the naltrexone and the placebo session (negative value denoting a reduction of the ratings by naltrexone) (B). The raincloud plots1 display the raw data (coloured dots), mean values and 95% confidence intervals (black dots/diamonds and bars) and probability distributions (vertical “clouds”). In (A), each dot represents the maximum relief/pleasantness rating averaged over 2 trials at the respective target pain intensity in the respective condition (PL or NX) for each participant (N = 27). In (B), each dot represents the difference in the averaged maximum relief/pleasantness ratings between the naltrexone and the placebo session for the respective target pain intensity for each participant. **P < 0.01. NX, naltrexone; PL, placebo.

3.2. Potential confounders

3.2.1. Naltrexone did not affect pain sensitivity

Naltrexone had no influence on participants’ self-regulated temperatures as well as pain unpleasantness and pain intensity ratings (Fig. 3; Table, Supplemental Digital Content 3, available at https://links.lww.com/PAIN/B355), suggesting no effect on pain sensitivity. The lack of naltrexone effects on the participants’ pain sensitivity was supported by an analysis of heat pain thresholds and heat tolerance thresholds (using the same GLMM procedure as described in naltrexone effects), which did not differ between naltrexone and placebo sessions (Figure, Supplemental Digital Content 4; Table, Supplemental Digital Content 3, available at https://links.lww.com/PAIN/B355). Integrated SCRs (after the onset of the painful phase or after the onset of the outcome phase) were neither influenced by naltrexone, in line with the absence of an effect of drug on perceptual pain responses (Figure, Supplemental Digital Content 4; Table, Supplemental Digital Content 3, available at https://links.lww.com/PAIN/B355). Bayes factor analyses supported anecdotal to moderate evidence for H0, ie, the absence of an effect of naltrexone, for all measures of pain sensitivity (Figure, Supplemental Digital Content 1; Table, Supplemental Digital Content 5, available at https://links.lww.com/PAIN/B355).

Figure 3.
Figure 3.: Naltrexone had no effect on participants’ self-regulated temperatures (A), pain unpleasantness (B), nor pain intensity ratings (C) at both target pain intensities “170” and “195”. The raincloud plots1 display the raw data (coloured dots), mean values and 95% confidence intervals (black dots/diamonds and bars), and probability distributions (vertical “clouds”). In (A), each dot represents the self-regulated temperature averaged over 2 trials with the same outcome phase (ie, relief or pleasantness) at the respective target pain intensity resulting in 2 datapoints per participant (N = 27) per raincloud plot. The same rule applies for pain unpleasantness ratings in (B) and pain intensity ratings in (C). ***P < 0.001. NX, naltrexone; PL, placebo.

Despite the absence of a naltrexone effect on perceptual and physiological pain responses, heat pain thresholds and heat tolerance thresholds were lower for women compared with men and integrated SCRs were greater after the onset of the painful phase compared with after the onset of the outcome phase (ie, pain relief) (Table, Supplemental Digital Content 3, available at https://links.lww.com/PAIN/B355), as expected from previous work.47 During the trials at target pain intensity “195”, smaller integrated SCRs were elicited compared with the trials at target pain intensity “170” (Table, Supplemental Digital Content 3, available at https://links.lww.com/PAIN/B355).

3.2.2. Participants’ mood was neither affected by naltrexone nor different between testing days

Changes in the POMS-Bi scores were not different between the naltrexone session compared with the placebo session (Figure, Supplemental Digital Content 4; Table, Supplemental Digital Content 3, available at https://links.lww.com/PAIN/B355). Bayes factor analyses supported anecdotal to moderate evidence for H0, ie, the absence of a drug:timepoint interaction effect, for all POMS-Bi scores (Figure, Supplemental Digital Content 1; Table, Supplemental Digital Content 5, available at https://links.lww.com/PAIN/B355).

Participants’ mood was also comparable between the 2 testing days because none of the POMS-Bi scores (“composed-anxious” subscore, “elated-depressed” subscore, and total score) was different between the naltrexone and the placebo sessions at baseline (before drug administration) (Figure, Supplemental Digital Content 4; Table, Supplemental Digital Content 3, available at https://links.lww.com/PAIN/B355).

A comparable emotional state of the participants on both testing days was further supported by the baseline resting HRV LF/HF component not differing between the naltrexone and placebo sessions (Figure, Supplemental Digital Content 4; Table, Supplemental Digital Content 3, available at https://links.lww.com/PAIN/B355).

The notion of comparable baselines of participants’ mood and emotional state between sessions was additionally supported by the Bayes factor analysis showing anecdotal evidence for H0, ie, no difference between sessions (Figure, Supplemental Digital Content 1; Table, Supplemental Digital Content 5, available at https://links.lww.com/PAIN/B355).

3.3. Pain relief was not associated with psychological factors

There was no correlation between PCS or TEPS consummatory scores and maximal relief and pleasantness ratings in the placebo session at either target pain intensity (rho’s ≤ 0.17, P‘s ≥ 0.38) (Figure, Supplemental Digital Content 6, available at https://links.lww.com/PAIN/B355), a result supported by Bayes factor analyses with anecdotal evidence for H0 for all correlations (Figure, Supplemental Digital Content 2; Table, Supplemental Digital Content 5, available at https://links.lww.com/PAIN/B355). In addition, neither PCS nor TEPS consummatory scores correlated with delta NX-PL relief or pleasantness ratings at either target pain intensity (rho’s ≤ |0.20|, P‘s ≥ 0.085) (Figure, Supplemental Digital Content 6, available at https://links.lww.com/PAIN/B355). Bayes factor analyses showed mixed evidence for correlations between PCS or TEPS consummatory scores and delta NX-PL relief or pleasantness. For all correlations, anecdotal evidence for H0 was suggested, except the following 5 correlations: PCS with delta NX-PL relief at “170”, PCS with delta NX-PL pleasantness at “170”, TEPS consummatory score with delta NX-PL relief at “170”, TEPS consummatory score with delta NX-PL pleasantness at “195”, and TEPS consummatory score with delta NX-PL relief at “195”. Despite favoring H1, none of these correlations were significantly different from 0 and were therefore not considered for further interpretation (Figure, Supplemental Digital Content 2; Table, Supplemental Digital Content 5, available at https://links.lww.com/PAIN/B355).

3.4. Individual pain relief was not related to individual decrease in pain relief by naltrexone

The high interindividual variability of relief/pleasantness ratings was the reason for exploring first, the intraindividual stability of participants’ relief/pleasantness ratings and second, a potential association between how much relief/pleasantness the participants reported in the placebo session and the magnitude of naltrexone effects on these relief/pleasantness ratings. Assessing the intraindividual variance of participants’ relief/pleasantness ratings across the 8 trials in the placebo session, a “moderate”-to-“good” test–retest reliability was observed (intraclass correlation coefficient = 0.76, 95% confidence interval = 0.65-0.86), indicating a stable rating behavior of the participants. Correlational analyses showed that individuals reporting higher relief/pleasantness ratings in the placebo session showed greater naltrexone effects on their relief/pleasantness ratings (relief ratings at target pain intensity “170”: rho = −0.37, P = 0.060; relief ratings at target pain intensity “195”: rho = −0.49, P = 0.016; pleasantness ratings at target pain intensity “170”: rho = −0.56, P = 0.0027; pleasantness ratings at target pain intensity “195”: rho = −0.43, P = 0.04). Because a random string A (here: relief/pleasantness ratings in the placebo session) will typically correlate with a random string B-A (here: the respective delta NX-PL), the observed correlation coefficients were compared with 10′000 randomly created correlation coefficients using inherently correlated samples A and B. All observed correlation coefficients fell within the 97.5% and 2.5% quantiles of the random correlation coefficient distribution, indicating that the observed effects did not differ from what would have been expected, given the flaw of A∼B-A and an inherent correlation of A and B (Table, Supplemental Digital Content 5, available at https://links.lww.com/PAIN/B355).

3.5. No side effects and successful blinding

Side effects (differences after placebo/naltrexone administration to before placebo/naltrexone administration) did not differ between placebo (35 minutes—before: median = 0, range = −4 to 3); end of session—before: median = 0, range = −4 to 4) and naltrexone sessions (35 minutes—before: median = 0, range = −2 to 2; end of session—before: median = 0, range = −3 to 13) (35 minutes after placebo/naltrexone administration—before placebo/naltrexone administration: Z = 0.33, P = 0.74; end of session—before placebo/naltrexone administration: Z = −1.50, P = 0.13). The absence of an effect of naltrexone on side-effect reports, ie, H0, was supported by Bayes factor analyses with anecdotal to moderate evidence for both timepoints after placebo/naltrexone administration (Figure, Supplemental Digital Content 1; Table, Supplemental Digital Content 5, available at https://links.lww.com/PAIN/B355).

The exit interview revealed that neither participants nor the experimenter identified placebo or naltrexone sessions better than by chance (participants: X2 = 0.087, df = 1, P = 0.77; experimenter: X2 = 1.85, df = 1, P = 0.17), indicating that blinding of participants as well as the experimenter was successful. Across both experimental sessions, participants correctly guessed placebo/naltrexone administration in 24 cases and incorrectly in 22 cases (“I do not know” in 8 cases). The experimenter was correct in 32 cases and incorrect in 22 cases (“I do not know” in 0 cases).

4. Discussion

This study investigated whether endogenous opioids play a role in mediating the feeling of pain relief in humans. Endogenous opioid blockade using naltrexone diminished self-reported relief in response to cooling after a painful heat stimulation. Pain sensitivity was not influenced by naltrexone. These results provide evidence that the feeling of pain relief in humans involves endogenous opioids.

The omission of an aversive stimulus is accompanied by 2 distinct processes: The negative valence of the stimulus is reduced and a feeling with a positive valence arises.51 In the case of nociceptive stimulation as an aversive stimulus, these 2 processes correspond to a reduction of perceived pain and an additional feeling of pain relief.29,49 The positive valence of pain relief has been demonstrated repeatedly29,30,49 and is reflected in this study by the highly correlated relief and pleasantness ratings (placebo session: r = 0.93, P < 0.001) in response to the relieving cooling stimulation. Not only is pain relief pleasant, it also has rewarding properties. In conditioned place preference paradigms, rodents prefer locations not previously paired with a painful stimulus over those previously paired, demonstrating that pain relief leads to negative reinforcement.26,38,39 Recently, Navratilova et al.39 have shown that this negative reinforcement associated with pain relief requires endogenous opioid activity, similarly to positively reinforced behavior by rewarding stimuli such as food.25,40 This study adds to these findings by demonstrating that endogenous opioids contribute to the positive feeling of pain relief in humans.

The average magnitude of the endogenous opioid blockade effect across participants (ranging from −8.13 to −4.71 points on the VAS) is comparable with observed reductions in placebo and relative relief-induced analgesia after opioid blockade.11,17 The exploratory analysis of how much pain relief the individuals reported in the placebo session and the magnitude of naltrexone effects on pain relief first revealed a negative association, ie, the greater the pain relief in the placebo session, the greater the naltrexone reduction of pain relief. However, the comparison to a randomly generated sample of 10′000 correlation coefficients showed that none of the observed correlations was different from what would be expected by the statistical flaw of a random string of numbers A typically correlating with a random string B-A using inherently correlated samples A and B. The observed high interindividual variability of perceived pain relief therefore seems not to be related to how pain relief is modulated by endogenous opioid blockade on an individual level. Nevertheless, interindividual differences in the endogenous opioid system might contribute to differences across individuals in how they perceived pain relief, similar to what has been described for pain perception37 and clinical opioid effects.33 It is also conceivable that the feeling of pain relief involves other neurotransmitter systems than endogenous opioids which would not be modulated by naltrexone. Besides, individuals may present with inherently different pain relief rating behaviors, as has been reported for pain ratings.8 Clinically relevant insights might be gained from future studies investigating the reasons for interindividual differences in the perception of pain relief.

Interestingly, relief/pleasantness ratings were not higher after more intense painful stimuli, in contrast to a previous report.29 This discrepancy might be explained by differences in the study designs: Leknes et al.29 used shorter stimuli (ie, 3 seconds compared with 30 seconds and 1 minute here) without capsaicin and subsequent cooling. In another experiment of the same study, cooling after painful heat was shown to increase relief ratings compared with painful heat without subsequent cooling.29 The combination of relatively long painful stimuli and subsequent cooling in this study might have resulted in a ceiling effect of relief/pleasantness ratings (mean of 62.45 and a 95th percentile of 91.25 at the lower target pain intensity “170” in the placebo session), thereby eliminating a potential association between pain relief and preceding pain intensity.

Nevertheless, care was taken in the study design to avoid that potential differences in perceived pain intensity between placebo and naltrexone sessions might impact relief ratings. For this reason, perception-adjusted, rather than temperature-adjusted, painful heat stimulations were used in this study. Pain intensity ratings did not differ between the naltrexone and placebo sessions, confirming successful pain intensity adjustment. Moreover, the temperatures required to reach the respective pain intensities (ie, “170” and “195”) neither differed between sessions, indicating that the participants’ pain sensitivity was comparable for naltrexone and placebo. The additional lack of naltrexone effects on pain unpleasantness ratings, heat pain thresholds, and heat tolerance thresholds, as well as autonomic nervous system responses (ie, SCRs), further confirm that naltrexone did not induce hyperalgesia in this study. This finding is in line with most studies assessing opioid antagonist effects on pain sensitivity in experimental pain paradigms [reviewed in Ref. 55]. The observation that SCRs were greater after painful stimuli compared with relieving stimuli is in line with a previous report,47 indicating that SCR recordings were valid. The finding of smaller SCRs in the trials with higher pain intensity (ie, “195”) compared with the “170” trials is probably explained by the order of the trials: The “195” trials were always performed after the “170” trials, which might have resulted in a habituation of the SCRs as demonstrated for repetitive painful electrical stimuli.13,44

The participants’ emotional state assessed by self-reports (ie, POMS-Bi) and autonomic responses (ie, HRV) did not differ between the naltrexone and the placebo session and could therefore be ruled out as a potential confounder of the finding that naltrexone diminished the feeling of pain relief. Furthermore, no effect of sex was observed, except for heat pain and heat tolerance thresholds being lower for women, in line with the literature on sex differences in pain sensitivity [reviewed in Ref. 18]. None of the assessed psychological factors, ie, pain catastrophizing and consummatory pleasure, was associated with pain relief, possibly because of the sample used here, ie, healthy, young volunteers. Future investigations in patient populations, eg, patients with chronic pain, might be of interest to examine the role of the psychological factors in pain relief.

The rewarding nature of pain relief is an important aspect in the clinical context. For instance, pain relief might reinforce behavioral strategies that are beneficial short-term, but maladaptive long-term. Indeed, operant learning with pain relief as negative reinforcement has been demonstrated in healthy controls and fibromyalgia patients who learned to increase sensitization and habituation responses to painful stimulation.6,7,23 The effectiveness of operant learning using pain relief as reinforcement might depend on neurochemical systems involved. Conceptually, there is a fundamental difference in whether the termination of an aversive stimulus is neurochemically reflected in a mere reduction in “substance A” (mediating the aversiveness of the stimulus) or by a release of “substance B” (mediating the subsequent pleasure). In the case of pain relief, this study provides evidence that the feeling of pain relief is at least partly mediated by an increase in “substance B”, namely endogenous opioids. Consequently, behaviors that provide pain relief may trigger addiction pathways [reviewed in Ref. 27]. This in turn might make the prevention of maladaptive behaviors providing pain relief more difficult. In addition, pain relief and its consequences, beneficial or maladaptive, might vary between individuals. This notion is suggested by the interindividual differences in pain relief and naltrexone effects on pain relief observed here and supported by previous literature on interindividual variability in endogenous opioid systems.33,37

5. Conclusion

Pain relief is rewarding and evokes a pleasant feeling in humans. Here, it is shown that the feeling of pain relief involves endogenous opioid signaling. Furthermore, the present results provide evidence of interindividual differences in experienced pain relief which merits closer investigation in future studies. Endogenous opioids mediating pain relief might contribute to its reinforcing properties, which, in a clinical context, are relevant regarding the acquisition and maintenance of behavioral strategies providing pain relief.

Finally, this study demonstrates the involvement of endogenous opioid signaling in the subjective feeling associated with the termination/reduction of nociceptive stimuli as aversive experiences. It would be interesting to investigate whether positive feelings associated with the reduction of aversive stimuli other than nociceptive stimuli are also mediated by endogenous opioids or whether other neurotransmitters are involved.

Conflict of interest statement

The authors have no conflicts of interest to declare.

Poster presentation at ZNZ Symposium 2020, ETH Zurich, Switzerland, September 10, 2020, and at the Annual Meeting of the Swiss Pain Society 2020, Bern, Switzerland, October 1 and 2, 2020. Poster presentation of a previous version: Canadian Pain Society Meeting, Charlottetown, Prince Edward Island, Canada, May 2015.

Appendix A. Supplemental digital content

Supplemental digital content associated with this article can be found online at https://links.lww.com/PAIN/B355.

Supplemental video content

A video abstract associated with this article can be found at https://links.lww.com/PAIN/B356.

Acknowledgments

This research was funded by a Canadian Institutes of Health Research grant (to P. Schweinhardt). L. Sirucek is supported by a Clinical Research Priority Program of the University of Zurich (CRPP Pain). The authors thank an anonymous reviewer for suggesting additional statistical analyses, which improved the quality of the manuscript.

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Pain relief; Endogenous opioids; Reward; Pain modulation; Pleasantness; Naltrexone; Opioid antagonist

Supplemental Digital Content

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.