Sex differences in pain: a brief review of clinical and experimental findings

Abstract

Recent years have witnessed substantially increased research regarding sex differences in pain. The expansive body of literature in this area clearly suggests that men and women differ in their responses to pain, with increased pain sensitivity and risk for clinical pain commonly being observed among women. Also, differences in responsivity to pharmacological and non-pharmacological pain interventions have been observed; however, these effects are not always consistent and appear dependent on treatment type and characteristics of both the pain and the provider. Although the specific aetiological basis underlying these sex differences is unknown, it seems inevitable that multiple biological and psychosocial processes are contributing factors. For instance, emerging evidence suggests that genotype and endogenous opioid functioning play a causal role in these disparities, and considerable literature implicates sex hormones as factors influencing pain sensitivity. However, the specific modulatory effect of sex hormones on pain among men and women requires further exploration. Psychosocial processes such as pain coping and early-life exposure to stress may also explain sex differences in pain, in addition to stereotypical gender roles that may contribute to differences in pain expression. Therefore, this review will provide a brief overview of the extant literature examining sex-related differences in clinical and experimental pain, and highlights several biopsychosocial mechanisms implicated in these male-female differences. The future directions of this field of research are discussed with an emphasis aimed towards further elucidation of mechanisms which may inform future efforts to develop sex-specific treatments.

Keywords: gender differences; opioid analgesics; pain; pain perception; sex differences.

Fig 1

Z-scores for multiple pain measures in a sample of healthy young adults (166 female, 167 male). Z-scores were computed such that the mean for the entire sample is 0. Higher Z-scores reflect lower pain sensitivity and lower Z-scores reflect higher pain sensitivity. Sex differences were statistically significant for all pain measures (P <0.05); however, the effect sizes ranged from small to large (Cohen's d in parentheses below), with a mean effect size in the moderate range (d=0.62). HPTH=heat pain threshold (d=0.48), HPTO=heat pain tolerance (d=0.98), IPTH=ischaemic pain threshold (d=0.24), IPTO=ischaemic pain tolerance (d=0.52), CPTH=cold pain threshold (d=0.41), CPTO=cold pain tolerance (d=0.55), PPTTrap=pressure pain threshold at the trapezius muscle (d=0.90), PPTMass=pressure pain threshold at the masseter muscle (d=0.89). Details regarding pain testing methods have been reported previously.