Advancing understanding of migraine pathophysiology and therapy by consideration of patient sex

Recent reports support the startling conclusion that peripheral nociceptors, the first link in pain transmission, are sexually dimorphic. The mechanisms promoting pain in men and women are therefore likely to be different, suggesting the need to consider patient sex as a factor in managing pain and painful conditions such as migraine. Many patients do not achieve sufficient benefit from available therapies and migraine therefore remains a major unmet medical need. The concept of sexual dimorphism in pain mechanism reveals previously unrecognized gaps in knowledge of migraine pathophysiology and in treatment outcomes. As migraine is highly female prevalent, our knowledge is based on studies conducted predominately in women. Data from these studies have rarely been analyzed and reported based on sex, limiting our interpretation of the occurrence, timing and severity of disease symptoms as well as possible differences in treatment efficacy in men. Inclusion of a higher proportion of men in both mechanistic investigations and clinical trials is therefore needed. Advancing our knowledge and improving therapeutic outcomes will require both preclinical and clinical investigations that address the contribution of sex in headache pain and other non-painful symptoms of migraine that impact the quality of life for patients. This viewpoint highlights the importance of considering sex as a variable in advancing our understanding of migraine pathophysiology and therapy. Consideration of patient sex could influence current clinical practice and the design of clinical studies.