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Sex differences in pain: a tale of two immune cells

Josiane C S Mapplebeck1, Simon Beggs, Michael W Salter

  • 1Program in Neuroscience & Mental Health, Hospital for Sick Children, Toronto, ON, Canada Department of Physiology, University of Toronto, Toronto, ON, Canada University of Toronto Centre for the Study of Pain, Toronto, ON, Canada.

Pain
|January 20, 2016
PubMed

Insights

Neuropathic pain mechanisms differ between sexes. In females, microglia do not drive pain hypersensitivity via P2X4 receptors, suggesting alternative pathways involving immune cells like T cells.

Area of Science:

  • Neuroscience
  • Immunology
  • Pain Research

Background:

  • Microglia are implicated in neuropathic pain through P2X4 receptor activation and brain-derived neurotrophic factor release, leading to neuronal disinhibition and pain hypersensitivity.
  • This established pathway was primarily elucidated using male rodents, overlooking potential sex-based differences in pain mechanisms.

Purpose of the Study:

  • To investigate the role of microglia and P2X4 receptors in neuropathic pain in female rodents.
  • To explore potential sex differences in the cellular mechanisms underlying neuropathic pain.

Main Methods:

  • Peripheral nerve injury model in rodents.
  • Analysis of microglial proliferation and P2X4 receptor expression in the spinal cord dorsal horn.
  • Assessment of pain hypersensitivity in male and female subjects.

Main Results:

  • Microglia proliferate in the dorsal horn in both sexes following nerve injury.
  • Females do not upregulate P2X4 receptors, unlike males.
  • Pain hypersensitivity in females appears to be mediated by a microglia-independent pathway, potentially involving adaptive immune cells.

Conclusions:

  • The role of microglia in neuropathic pain is sexually dimorphic.
  • Females utilize a different cellular pathway, possibly involving T cells, to mediate pain hypersensitivity.
  • Preclinical pain research must include both sexes to fully understand and treat neuropathic pain.

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