Pain: sex differences and implications for treatment.

Women have a higher prevalence than men of several clinical pain conditions and of inflammation-mediated disorders. There is also increasing evidence for sex differences in sensitivity to experimental pain and in the response to analgesics. Estrogen, progesterone, and other gonadal hormones have a complex role in inflammatory processes and the pain response. Microglia cells in the central nervous system, which have sex hormone receptors, become activated in response to inflammatory stimuli, releasing cytokines and other mediators that are pronociceptive and can amplify the pain response. Although the mechanisms underlying sex differences in pain and analgesia have not been fully elucidated, both peripheral and central nervous systems pathways may be involved. Sex differences in the opioid, dopaminergic, serotoninergic, and other pain-related systems have been documented; and some evidence suggests that differences are most pronounced during the peak reproductive years. Psychosocial factors also play an important role. Given the important role of inflammation in mediating pain, nutritional factors that modulate the inflammatory response offer a promising and exciting new avenue for the prevention and treatment of chronic pain disorders. Of particular interest is the potential role of moderate- to high-dose vitamin D and omega-3 fatty acid supplements, both of which have powerful anti-inflammatory effects. These nutritional interventions, which influence cytokine, leukotriene, and prostaglandin pathways, may be of particular benefit to women due to their higher prevalence of inflammatory chronic pain disorders. The recent launch of a new large-scale randomized trial of these nutritional supplements provides an opportunity to assess their potential antinociceptive role. Additional research is needed to clarify the mechanisms for sex differences in pain and to develop new treatment modalities that improve pain management for both men and women.