Sex differences in mechanisms of pain hypersensitivity

Neurosci Biobehav Rev. 2024 Aug:163:105749. doi: 10.1016/j.neubiorev.2024.105749. Epub 2024 Jun 3.

Abstract

The introduction of sex-as-a-biological-variable policies at funding agencies around the world has led to an explosion of very recent observations of sex differences in the biology underlying pain. This review considers evidence of sexually dimorphic mechanisms mediating pain hypersensitivity, derived from modern assays of persistent pain in rodent animal models. Three well-studied findings are described in detail: the male-specific role of spinal cord microglia, the female-specific role of calcitonin gene-related peptide (CGRP), and the female-specific role of prolactin and its receptor. Other findings of sex-specific molecular involvement in pain are subjected to pathway analyses and reveal at least one novel hypothesis: that females may preferentially use Th1 and males Th2 T cell activity to mediate chronic pain.

Keywords: Hypersensitivity; Pain; Pathway analyses; Sex difference.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Female
  • Humans
  • Hyperalgesia / physiopathology
  • Male
  • Microglia / metabolism
  • Microglia / physiology
  • Pain / metabolism
  • Pain / physiopathology
  • Prolactin / metabolism
  • Sex Characteristics*
  • Spinal Cord / metabolism
  • Spinal Cord / physiopathology

Substances

  • Calcitonin Gene-Related Peptide
  • Prolactin