Sex-specific pain relief: Study reveals distinct biological pathways in men and women
New research reveals that men and women rely on distinct biological mechanisms for pain relief, potentially explaining sex differences in chronic pain prevalence and opioid treatment efficacy.
Groundbreaking research from the University of California San Diego School of Medicine has uncovered fundamental differences in how men and women experience pain relief. The study, which combined data from two clinical trials involving both healthy individuals and those with chronic lower back pain, found that men primarily rely on endogenous opioids – the body’s natural painkillers – to alleviate pain. In contrast, women appear to utilise non-opioid pathways for pain reduction.
Different pathways to pain relief
The research team, led by Dr Fadel Zeidan, professor of anesthesiology and Endowed Professor in Empathy and Compassion Research at UC San Diego Sanford Institute for Empathy and Compassion, conducted a series of experiments involving meditation training and the administration of naloxone, a drug that blocks both synthetic and endogenous opioids.
Participants underwent a meditation training programme and then practised meditation while receiving either a placebo or a high dose of naloxone. Simultaneously, they were subjected to a painful but harmless heat stimulus applied to the back of the leg. The researchers measured and compared the level of pain relief experienced from meditation when the opioid system was blocked versus when it was intact.
The results were striking. For men, blocking the opioid system with naloxone significantly inhibited meditation-based pain relief, suggesting that they rely heavily on endogenous opioids to reduce pain. In women, however, naloxone actually increased meditation-based pain relief, indicating that they rely on non-opioid mechanisms for pain reduction.
Implications for chronic pain and opioid use
These findings have significant implications for understanding sex differences in chronic pain prevalence and treatment efficacy. Women are known to have a higher prevalence of chronic pain conditions and often respond poorly to opioid therapies compared to men.
Dr Zeidan commented on the potential implications of these findings: “Although speculative, our findings suggest that maybe one reason that females are more likely to become addicted to opioids is that they’re biologically less responsive to them and need to take more to experience any pain relief.”
The study also found that individuals with chronic pain experienced greater pain relief from meditation compared to healthy participants, regardless of sex. This suggests that meditation may be particularly effective for managing chronic pain conditions.
A new approach to pain management
The research underscores the need for more sex-specific approaches to pain treatment. By tailoring pain therapies to an individual’s sex, it may be possible to improve patient outcomes and reduce reliance on opioids, which carry significant risks of dependence and addiction.
“These results underscore the need for more sex-specific pain therapies, because many of the treatments we use don’t work nearly as well for women as they do for men,” said Dr Zeidan.
He added, “This study provides the first clear evidence that sex-based differences in pain processing are real and need to be taken more seriously when developing and prescribing treatment for pain.”
Methodological strengths and limitations
The study combined data from two clinical trials, involving a total of 98 participants. This relatively large sample size and the inclusion of both healthy individuals and those with chronic pain strengthen the generalisability of the findings.
However, it’s important to note that the study did not measure endocannabinoid concentrations, menstrual cycle, or gonadal hormone levels – factors known to play a role in sex-based pain differences. Future research incorporating these measures could provide a more comprehensive understanding of the mechanisms underlying sex differences in pain processing.
Meditation as a pain management tool
An interesting secondary finding of the study was that extensive mental training is not required to elicit the capacity to directly reduce acutely evoked pain through meditation. This suggests that meditation could be a valuable tool for pain management, even for individuals with limited prior experience.
The research also found that individuals with chronic pain produced greater meditation-induced analgesia (-18%) than pain-free individuals (-3%). This indicates that meditation may be particularly beneficial for those suffering from chronic pain conditions.
Looking ahead
This research opens up new avenues for exploring sex-specific pain treatments and understanding the complex interplay between biological sex and pain processing. As our understanding of these differences grows, it may lead to more effective, personalised approaches to pain management that take into account an individual’s sex and unique biological makeup.
Future studies could explore whether these sex differences in pain processing extend to other forms of pain relief beyond meditation and investigate the specific non-opioid mechanisms that women rely on for pain reduction. Such research could potentially lead to the development of new pain therapies that are more effective for women.
Reference:
Dean, J. G., Reyes, M., Oliva, V., et. al. (2024). Self-regulated analgesia in males but not females is mediated by endogenous opioids. PNAS Nexus, pgae453. https://doi.org/10.1093/pnasnexus/pgae453
