Sex-specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury

Abstract

Recent studies have suggested a sexually dimorphic role of microglia in the maintenance of neuropathic pain in rodents. Here, we utilized RNA sequencing analysis and in vitro primary cultures of microglia to characterize the sex differences in microglia in pain-related regions in nerve injury and chemotherapy-induced peripheral neuropathy mouse models. Whilst mechanical allodynia and behavioral changes were observed in all models, transcriptomic analysis revealed a substantial change in microglial gene expression only within the ipsilateral lumbar spinal cord 7-days after nerve injury. Both sexes upregulated genes associated with inflammation, phagosome, and lysosome activation, though males revealed a prominent global transcriptional shift not observed in female mice, reflecting acute activation. Further, in vitro studies revealed that only male microglia from nerve-injured mice developed a reactive phenotype with increased phagocytotic activity. This study indicates distinct sex differences in spinal microglia and suggests they contribute to the sex-specific pain processing following nerve injury.

Meta-Analysis on the Effects of Electric Acupuncture on Neural Functional Recovery and Related Pathways of Rats after Spinal Cord Injury

“…It mediates the transfer of inflammatory cytokines, causes the collapse and retraction of growth cones, and induces apoptosis of glial cells and neurons, thereby inhibiting axonal elongation. Therefore, inhibition of this signaling pathway is an important target in the treatment of spinal cord injury [12,13].…”

Conserved transcriptional programming across sex and species after peripheral nerve injury predicts treatments for neuropathic pain

“…The primary afferent neurons in peripheral nerves project into the dorsal horn of the spinal cord, which is the critical first site in the CNS for integrating, processing, and transmitting pain information. Transcriptomic changes in the dorsal horn produced by peripheral nerve injury have been increasingly described (7)(8)(9)(10) with a large emphasis on characterizing sex differences in changes in gene expression. Such studies are touted to hold promise to characterize pathological biochemical pathways that might in the future reveal targets for new therapies.…”