Sex differences in pain along the neuraxis

• Published in: Neuropharmacology Vol. 210; p. 109030
• Main Authors: Presto, Peyton, Mazzitelli, Mariacristina, Junell, Riley, Griffin, Zach, Neugebauer, Volker
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2022
• Subjects: Behavior; Central Nervous System; Chronic Pain; Female; Humans; Male; Neuroimmune signaling; Neurophysiology; Pain; Sex Characteristics; Sex differences; Sex Factors; Transcriptomics; Neuroimmune signaling; Sex differences; Pain; Behavior; Transcriptomics; Neurophysiology
• ISSN: 0028-3908; 1873-7064; 1873-7064
• DOI: 10.1016/j.neuropharm.2022.109030

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. This article is part of the Special Issue on ‘Advances in mechanisms and therapeutic targets relevant to pain’. •Sex differences in pain processing and pain modulation exist at the molecular, cellular, and systems levels.•Sex differences are influenced by genetic, hormonal, and neuroimmune factors that may differ across the neuraxis.•Well-documented greater “pain sensitivity” in females may not extend to emotional-affective or cognitive pain components.•Sex differences in pain resilience are not clear as the mechanisms of these dimensional differences are largely unknown.•Important knowledge gaps include sexual dimorphisms in neuroimmune signaling and in brain regions involved in pain.