Sex and gender differences in pain have clinical and biological implications for medical practice

For clinicians, understanding how sex and gender influence pain is not an academic exercise. These differences affect diagnostic patterns, treatment responses, healthcare use, disability outcomes, and patient–provider communication. Failure to account for them risks both underrecognition and suboptimal management of pain in men and women.In this article, the term “sex” refers to biologically determined attributes (chromosomes, reproductive organs, hormonal milieu), while “gender” refers to socially and culturally shaped roles, behaviours and expectations that influence pain expression and coping.Differences seen in clinical populationsLarge epidemiological studies and systematic reviews consistently demonstrate that many common pain conditions are more prevalent in women than in men. These include: General headaches (up to three-fold higher prevalence); Migraine (three-to-four-fold higher); Temporomandibular disorders (TMD) (two-to-three times higher); Burning mouth syndrome (two-to-three times higher); Shoulder pain (approximately two-fold higher); Knee pain (approximately 1.5-to two times higher); Fibromyalgia (four-to-seven-fold higher). Furthermore, across populations, women are more likely to report multisite pain, known risk factor for chronicity and disability. While prevalence rates vary by condition, age, and methodology, the overall pattern is robust across countries and cultures. However, sex differences tend to diminish after the seventh decade of life, likely reflecting hormonal, survivorship and cohort effects.Women use healthcare services more frequently than men for both painful and non-painful conditions, including specialty pain clinics. Conversely, women are more likely to adhere to physician-recommended activity restrictions.Sex differences also appear in occupational outcomes. Studies of injured workers suggest that men return to work sooner but experience higher rates of recurrent disability, whereas women take longer to return but demonstrate greater long-term work stability. These patterns likely reflect differences in job demands, domestic responsibilities and social roles rather than biological vulnerability alone.The differences between sexes are shown as well in experimental settings using thermal, mechanical, ischemic, and chemical painful stimuli with women, on average, exhibiting lower pain thresholds and tolerance than men. These rather modest differences in magnitude are highly reproducible. What accounts for these differences?We can better understand sex-related differences in pain perception by recognizing that the experience of pain is the composite sum of complex and dynamic interactions—a mixture of biological, psychological social and cultural factors. Our gonadal hormones (estrogens, progesterone and testosterone) play a big role in these differences. These hormones modulate neurotransmitter systems, cytokine signaling and neuroplasticity, and influence virtually every system related to pain processing, including peripheral nociceptors; spinal cord dorsal horn signaling; descending inhibitory and facilitatory pathways; immune and inflammatory responses; and central affective–motivational circuits. The effects not only have implications for pain sensitivity but also for drug metabolism, inflammatory responses to injury and recovery trajectories.Another factor contributing to pain differences between the sexes are sex-specific gene expression and neuroimmune mechanisms. Preclinical studies demonstrate that males and females may rely on different immune cell pathways (e.g., microglia versus T-cells) for pain sensitization. This raises the possibility that optimal analgesia may be achieved by sex-specific targets.Men and women differ not only in pain perception but also in responses to analgesic medications and in the activation of endogenous pain-modulating systems. Only in recent decades regulatory bodies such as the U.S. Food and Drug Administration emphasized the importance of sex-specific drug responses. For example, limited data suggest that women may exhibit a reduced analgesic response to certain NSAIDs (e.g., ibuprofen), though evidence remains sparse; some postoperative studies indicate that men require higher opioid doses for comparable analgesia, although findings are inconsistent; Also women appear to derive greater analgesic benefit from K-opioid receptor–mediated mechanisms, a difference observed in both experimental and clinical settings.Cultural, ethnic and gender norms. While sex differences reflect biology, gender profoundly shapes how pain is interpreted, expressed and communicated. Gender norms influence pain behaviour from early childhood. In almost every culture we see boys taught to suppress pain expression (“tough it out”), whereas girls may receive greater permission to verbalize distress. Even in experimental studies, men and women describe and communicate pain differently: Men are more likely to report embarrassment and reluctance to complain, while women more readily acknowledge pain and seek interpersonal support. In general, cultural background influences beliefs about stoicism, suffering, legitimacy of pain and help-seeking behaviours. Most importantly, sex and culture interact, so that gender expectations are expressed differently across societies, reinforcing or attenuating observed sex differences in pain. Even more, gender stereotypes influence not only self-perception but physiological responses to pain. For example, experimental studies have shown that men “report less pain when tested by an attractive female experimenter” (what I call in my teachings to physicians the “peacock phenomenon”), while this effect is not observed when the experimenter is male or has a rather “neutral (or “no good-looking”) appearance! Similarly, those who strongly identify with traditional masculine or feminine roles, display higher physiological stress responses if they are exposed to a pain task that challenges their male or female identities. The bottom line is that “threats to gender identity” magnify stress and pain, and highlight how important is the context in pain assessment and research.Coping styles, catastrophizing and emotional distress. Finally, men and women differ in coping strategies. Men tend to favour approaches focussing “how to solve a problem,” while women more often emphasize emotional processing and social support. Women report higher levels of pain catastrophizing (a well-established predictor of pain intensity, disability, and poor treatment outcomes across pain conditions), characterized by rumination, helplessness and magnification of threat. Again, this is confirmed in laboratory studies where catastrophizing influences experimental pain responses (variable across sex and culture). Finally, pain and negative affect are bidirectionally linked. Women, on average, report higher levels of psychological distress, depression and somatic awareness. Social norms may also make emotional disclosure more acceptable for women than for men.Clinical implications and key pointsSex and gender differences in pain are real, clinically relevant, and multifactorial. They influence prevalence, perception, communication, treatment response, and outcomes. Recognizing these differences allows clinicians to avoid simplistic assumptions, reduce bias and move toward more individualized, equitable pain care.Key points for cliniciansWomen experience higher prevalence and multisite pain across most pain conditions.Biological factors include sex hormones, genetics, immune responses and neurobiology.Gender roles influence pain expression, coping strategies and help-seeking behaviour.Analgesic responses differ by sex, but data remain limited due to historical underrepresentation.Catastrophizing and psychological distress play a larger role in pain outcomes for women.Pain assessment and management should explicitly consider sex and gender influences.Dr. Angela Mailis is a specialist in Physical Medicine and Rehabilitation and the director and founder of the Pain and Wellness Centre, a chronic pain clinic in Vaughan Ont. She also hosts a YouTube channel that provides explanations of complex topics on pain for a patient audience. References: Fillingim RB, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley JL. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain. 2009;10(5):447–485.Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci. 2012;13(12):859–866.Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013;111(1):52–58.Greenspan JD, Craft RM, LeResche L, et al. Studying sex and gender differences in pain and analgesia: a consensus report. Pain. 2007;132(Suppl 1):S26–S45.Wiesenfeld-Hallin Z. Sex differences in pain perception. Gend Med. 2005;2(3):137–145.Keogh E. Sex differences in pain coping: a selective review. Pain. 2006;121(3):179–191.Sullivan MJL, Thorn B, Haythornthwaite JA, et al. Theoretical perspectives on the relation between catastrophizing and pain. Clin J Pain. 2001;17(1):52–64.