Healthy women show more experimentally induced central sensitization compared with men.

Women more often experience chronic pain conditions than men. Central sensitization (CS) is one key mechanism in chronic pain that can differ between the sexes. It is unknown whether CS processes are already more pronounced in healthy women than in men. In 66 subjects (33 women), a thermal CS induction protocol was applied to the dorsum of one foot and a sham protocol to the other. Spatial extent [cm2] of secondary mechanical hyperalgesia (SMH) and dynamic mechanical allodynia were assessed as subjective CS proxy measures, relying on verbal feedback. Changes in nociceptive withdrawal reflex magnitude (NWR-M) and response rate (NWR-RR) recorded through surface electromyography at the biceps and rectus femoris muscles were used as objective CS proxies. The effect of the CS induction protocol on SMH was higher in women than in men (effect size 2.11 vs 1.68). Nociceptive withdrawal reflex magnitude results were statistically meaningful for women (effect size 0.31-0.36) but not for men (effect size 0.12-0.29). Differences between men and women were not meaningful. Nociceptive withdrawal reflex response rate at the rectus femoris increased in women after CS induction and was statistically different from NWR-RR in men (median differences of 13.7 and 8.4% for 120 and 140% reflex threshold current). The objective CS proxy differences indicate that dorsal horn CS processes are more pronounced in healthy women. The even larger sex differences in subjective CS proxies potentially reflect greater supraspinal influence in women. This study shows that sex differences are present in experimentally induced CS in healthy subjects, which might contribute to women's vulnerability for chronic pain.