Abstract
Despite the overwhelming female-predominance in chronic pain disorders, preclinical pain studies have historically excluded females as research subjects. Male-biased explanations of pathological pain mechanisms may not fully translate to pain processes in females, necessitating the exploration of pain processing and modulation in both sexes at the preclinical and clinical levels. This review highlights historical trends in the study of sex differences within the pain field and examines the current literature regarding new techniques for the mechanistic analysis of pain modulation in males and females. A large body of evidence suggests that sex differences exist at the molecular, cellular, and systems levels of pain processing, likely influenced by a combination of genetic, hormonal, and neuroimmune factors that may differ at distinct levels of the neuraxis.