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Pain perception and responses to analgesics are influenced by both biological sex and gender-related factors. The findings challenge the long-standing practice of applying a universal approach to pain management and support a more individualized understanding of how patients experience and respond to pain.
Pain treatment is often based on standardized dosing, but a novel narrative review suggests that biological sex and socio-cultural gender can substantially influence how pain is processed and how analgesics work. The review, led by Dominika Domińczak et al., examined recent experimental and clinical evidence on pain neurobiology, neuroimmunology, pharmacokinetics, and treatment outcomes, revealing important differences between males and females.
From microglia to T-cells: different pathways, same pain
One of the most notable findings concerns the immune mechanisms underlying chronic pain. Microglia appear to play a dominant role in chronic pain in males, whereas T-cells have a greater role in females.
This sex-specific neuroimmune response may help explain why patients can experience and respond to pain treatments differently—even when they have apparently similar pain conditions.
Women may process medicines differently
The review also identified numerous pharmacokinetic differences in females. Compared with males, females tend to have:
Together, these differences can alter drug concentrations, clearance, therapeutic effects, and toxicity.
The analgesic response is not one-size-fits-all
The biological differences may have direct clinical consequences. Women may experience different efficacy profiles and a higher risk of adverse drug reactions with non-steroidal anti-inflammatory drugs (NSAIDs) and μ-opioids. I
nterestingly, κ-opioid receptor agonists may provide superior analgesia in females, pointing towards the potential value of sex-specific approaches to analgesic selection.
Could personalised pain treatment close the “pain gap”?
The authors argue that universal analgesic dosing may leave some patients—particularly women—with inadequate pain relief or increased drug toxicity. They call for sex to be routinely considered as a biological variable in pain research, alongside greater use of Sex and Gender Equity in Research (SAGER) guidelines.
The message is clear: the future of pain management may not be “one dose fits all.” Recognizing how sex and gender shape pain pathways and drug responses could help move clinical care towards more equitable and genuinely personalised pain medicine.
Journal of Education, Health and Sport
From Microglia to Stereotypes: The Impact of Sex and Gender on Pain Perception and Analgesic Response
Dominika Domińczak et al.
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