Genes May Explain Why Gabapentin Works for Some Pain Patients

By Pat Anson

Over the years, gabapentin (Neurontin) has been prescribed for dozens of health conditions, from epilepsy and fibromyalgia to depression and post-operative pain. It’s even been used to treat bipolar disorder. Gabapentin has been marketed for so many different conditions – at times illegally -- that a pharmaceutical company executive infamously referred to the drug as “snake oil.”

Even though it’s been approved for medical use for over 30 years, the UK’s National Health Service admits it’s still “not clear exactly how gabapentin works.”

A new study may finally help explain why gabapentin is an effective pain medication for some patients and an addictive drug with unwelcome side effects for many others.

It could be all in the genes.

Researchers at the University of Edinburgh took another look at a previous study of women with chronic pelvic pain to see why gabapentin worked no better than a placebo for most, but was a moderately effective pain reliever for about 40% of them.

Researchers took saliva samples from 71 women who participated in the study -- 29 who responded to gabapentin and 42 who had no improvement -- and found that the responders were more likely to have a variation of the gene Neuregulin 3 (NRG3). The gene is primarily expressed in the brain, spinal cord and central nervous system, and helps regulate pain sensation and transmission.

The findings, recently published in the journal iScience, may explain why gabapentin works for some women with chronic pelvic pain.

"A genetic factor that can predict how well gabapentin will work in patients offers the prospect of tailored treatment, and provides invaluable insights into understanding chronic pain. We hope eventually to use this genetic marker to optimize personalized treatment decisions and minimize adverse effects for women with chronic pelvic pain," wrote lead author Scott Mackenzie, MD, from the University of Edinburgh's Centre for Reproductive Health.

The study also has implications for other chronic pain conditions. Further research is needed to confirm the findings, but researchers say a genetic test for NRG3 could help limit the use of gabapentin to people who actually benefit from the drug.

"Isolating this single genetic marker is an important discovery that could ultimately help refine treatments for millions of women worldwide who suffer from chronic pelvic pain, as well as increasing our understanding of its role in other pain conditions. We believe this is an exciting opportunity for collaboration with a commercial partner who can help translate the research into a clinical setting," said Susan Bodie, PhD, Head of Business Development for the College of Medicine and Veterinary Medicine at the University of Edinburgh.

Gabapentin and other nerve drugs like pregabalin (Lyrica) have come under increased scrutiny in the UK because they are increasingly involved in overdose deaths.  

A recent analysis of drug tests suggests that gabapentin is also being misused in the U.S. Gabapentin was found in in over 13% of urine samples that tested positive for fentanyl -- about twice the number of drug tests in which prescription opioids were found.

Despite the risks of side effects and addiction, gabapentin is increasingly prescribed “off-label” for conditions it is not approved to treat, such as dental pain. A 2019 study found little evidence that gabapentin and pregabalin should be used for pain and said their effectiveness was often exaggerated by prescribing guidelines.

The CDC’s revised opioid guideline says gabapentin and pregabalin can have “small to moderate improvements” on pain, but with a moderate risk of side effects.

Let’s Talk About Chronic Pain and Sex

By Ann Marie Gaudon, PNN Columnist

Do you remember that catchy song from the early 90’s by the hip hop group Salt-N-Pepa called “Let’s Talk About Sex”? I sure do and I still think it’s fun!

For many people, sexual activity and intimacy are incredibly important factors of living well, being happy, and feeling close to one another. But when chronic pain enters a life, those factors may take a big hit. People don’t talk enough – or at all – about living in pain and sexual intimacy.

Let’s talk now baby!

In my many years of being with people in pain, I’ve seen sex become a taboo subject. It can be denied not only to another, but to oneself as well. It gets complicated when the person in pain worries about their physical performance or if they can even engage in sexual activity without increasing their pain.

This most certainly affects self-esteem and confidence in the bedroom. Then we have a situation where everybody stops talking -- when they should be doing just that.

Why does sex matter if you have chronic pain?

It matters and can have a significant impact on your quality of life. Something amazing happens when you are the recipient of wanted sexual touching and intimacy. Your body will release endorphins, which are the body's natural pain reducers. You will feel better and happier, not to mention all those other good feelings you may experience.

The name endorphin comes from “endogenous morphine,” which means they come from inside the body and mimic the effects of morphine. For that reason alone, I tell my clients to have more sex if possible. And if they are single, to get busy masturbating. An orgasm is an orgasm, and your body doesn’t care how it gets there. Just get there.

In 2017 a functional MRI study was conducted measuring brain activity in women during orgasm. “Brain activity gradually increased leading up to orgasm, peaked at orgasm, and then decreased,” researchers found. This activation included many regions of the brain, including those that process rewarding experiences such as food and sex. 

Another study from 2013 shows that orgasm may have the ability to decrease or alleviate headache pain. Want better sleep? Have regular orgasms. Yet another study in 2015 showed the mediating effect of sexual activity on pain and depression for those suffering from low back pain.  

How are you going to have sex if you have back pain?

I found out that the clinical community was in contact regularly with Canadian Dr. Stuart McGill, Chief Scientific Officer for Backfitpro and a distinguished professor emeritus at Waterloo University. McGill is asked repeatedly by clinicians about couples who are celibate because of back pain. Are there any guidelines on sexual technique that can reduce the risk of more pain?

The challenge was on! Professor McGill and graduate student N. Sidorkewicz conducted the only study in the world that took real couples and measured their spine postures and muscle activity while engaged in various sexual positions. This was no small feat, considering the challenges of recruitment, instrumentation and developing an experimental protocol that satisfied the ethics research committee and requests from the medical community. 

The study measured muscle activity and 3D spine and body movements, using the very same technology that was used in the making of Avatar. The object was to create an atlas of sexual positions that did not trigger back pain.

Professor McGill has a short version of a sexual atlas in his book "Back Mechanic," which includes spine-sparing positions that enable sex for people with back problems. The book guides the reader through a self-assessment of their pain triggers. Then, based on the specific trigger, positions and movements are shown to consider and to avoid.

I am super impressed with this work and I only wish that we had guidelines for virtually every source of pain.

Are there other pain conditions that defy sexual activity?

You bet there are! One that comes to mind is pelvic floor dysfunction or PFD. I have known many people with this diagnosis. We all have a pelvic floor, whether you were born with a penis or vagina, and so no one is immune to PFD.

One female patient with this diagnosis -- more specifically “hypertonic pelvic floor muscles” -- told me that just a light touch and/or engorgement from arousal can be enough to create excruciating muscle spasms.

“Spasms beget spasms,” she said. “It is very, very painful and truly sad that we avoid intimacy. I have a Pavlovian response developed over many years of severe pain and flares that lasted for days.”

The forceful, rhythmic contractions that occur for anyone having an orgasm can set off a cascade of painful symptoms. Here are links two simple videos to explain male and female pelvic pain.

PFD is currently treated by specialized physical therapists and yes – there are success stories, thankfully.

How do I get busy?

As a person with any type of pain, you may need to get creative. You may need to adjust positions for yourself or your partner, as well as the time, day and even the environment. If you require minimum body movement, consider self-stimulation while lying beside your partner. Sex toys and lubricants also work wonders, whether you have a partner or are alone.

If being spontaneous is not in the plan, consider making intimate dates either with a partner or yourself. Above all, keep the communication open with your partner. It’s crucial that you understand each other and have realistic expectations without judgment.

If you’re wondering if you can share intimacy without the orgasm, the answer is yes! Orgasm is only one aspect of sexual intimacy, and you can connect and feel great in plenty of other ways.

There comes a time in many couple relationships when sexual intercourse isn’t an option, due to physical, emotional or mental health. When this occurs, there are many alternatives to consider. Make a list for yourself, considering your unique needs, which will support and care for your pained body no matter what stage in life you are in. 

Ann Marie Gaudon is a registered social worker and psychotherapist in the Waterloo region of Ontario, Canada with a specialty in chronic pain management.  She has been a chronic pain patient for over 30 years and works part-time as her health allows. For more information about Ann Marie's counseling services, visit her website. 

Brain Scans Link Fibromyalgia and Pelvic Pain

By Pat Anson, Editor

Fibromylagia and urological pelvic pain would seem to have little in common. The former causes widespread body pain, while the latter is marked by chronic inflammatory pain in the bladder or prostate.

But researchers at the University of Michigan have stumbled upon something that both conditions share – besides being difficult to treat.

While examining MRI brain scans of over 1,000 participants enrolled in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network  -- also known as the MAPP study – they found that people with fibromyalgia or chronic urological pelvic pain both have increased “gray matter” in their brains. Gray matter is tissue in the brain that helps transfer signals between nerves.

"Interestingly, when we put these individuals into the brain imaging scanner, we found that those who had widespread pain had increased gray matter and brain connectivity within sensory and motor cortical areas, when compared to pain-free controls," says Richard Harris, PhD, an associate professor of anesthesiology and rheumatology at Michigan Medicine.

Harris and colleagues want to know if widespread pain, thought to be a marker of centralization in the nervous system, actually originates in the brain. So it was a bit of a surprise to find additional gray matter in the brains of people with urological pelvic pain, a condition that can be caused by interstitial cystitis or chronic prostatitis.

"What was surprising was these individuals with widespread pain, although they had the diagnosis of urological chronic pelvic pain, were actually identical to another chronic pain disorder: fibromyalgia," said Harris.

In addition to the MRI scans, study participants were also asked to draw on a body map where they were experiencing pain. Many of those with pelvic pain indicated they had widespread body pain.

"This study represents the fact that pelvic pain patients, a subset of them, have characteristics of fibromyalgia," Harris says. "Not only do they have widespread pain, but also they have brain markers indistinguishable from fibromyalgia patients."

Harris hopes the study will lead to new ways of treating chronic pain -- as there might be similarities across pain conditions if both show widespread pain.

"We think that this type of study will help treat these patients because if they have a central nerve biological component to their disorder, they're much more likely to benefit from targets that affect the central nervous system rather than from treatments that are aimed at the pelvic region," Harris said.