From Microglia to Stereotypes: The Impact of Sex and Gender on Pain Perception and Analgesic Response
DOI:
https://doi.org/10.12775/JEHS.2026.93.72629Keywords
sex characteristics, gender bias, pain perception, pharmacokinetics, analgesics, precision medicineAbstract
Background: Despite the shift towards personalized medicine, pain management frequently relies on universal dosing based on a standard male model. Both biological sex and socio-cultural gender significantly influence nociception and treatment efficacy, contributing to the clinical "pain gap" and unequal care.
Aim: To systematize current knowledge regarding sex-specific differences in pain neurobiology, perception and the pharmacokinetics of commonly used analgesics.
Materials and methods: A narrative literature review was concluded, analyzing recent experimental and clinical studies focusing on pain neuroimmunology, pharmacokinetics and clinical outcomes in both sexes.
Results: Evidence demonstrates marked sexual dimorphism in pain processing. Chronic pain is mediated by microglia in males and T-cells in females. Pharmacokinetically, females exhibit a higher volume of distribution for lipophilic drugs and higher CYP3A4 activity, but slower phase II metabolism and lower glomerular filtration rates. Clinically, this translates to distinct efficacy profiles and higher risks of adverse drug reactions for NSAIDs and mu-opioids in women, whereas kappa-opioids agonists provide superior analgesia in females.
Conclusions: Universal analgesic dosing is inadequate, often exposing women to suboptimal pain relief and increased toxicity. Integrating sex as a biological variable and implementing SAGER guidelines in future research are essential for equitable, precision pain medicine.
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Copyright (c) 2026 Dominika Domińczak, Aleksandra Kurek, Aleksandra Głowacka, Anhelina Kaminskaya, Hubert Feretycki, Aladdin Salama, Tetiana Savchak, Patryk Górecki, Sofiia Ivanchuk, Shafea Abdulla
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