Dermal macrophages control tactile perception under physiological conditions via NGF signaling

Sci Rep. 2024 Nov 8;14(1):27192. doi: 10.1038/s41598-024-78683-x.

Abstract

We demonstrated previously that sorting nexin 25 (SNX25) in nerve-associated macrophages plays critical roles in pain sensation by regulating tissue NGF content under both physiological and neuropathic conditions. In the present study, we apply the SNX25-NGF paradigm to tactile perception by showing that Snx25+/- mice or macrophage-specific Snx25 conditional knock-out (mcKO) mice had weaker responses to tactile stimuli in normal conditions. Snx25 mcKO mice responded poorly to transcutaneous electrical stimuli at a frequency of 5 Hz (C fiber responses), but normally to stimuli at a frequency of 250 Hz (Aδ fiber responses) or of 2000 Hz (Aβ fiber responses). CX3CR1-positive dermal macrophages were frequently found near calcitonin gene-related peptide (CGRP)- positive nerves and, less frequently, tyrosine hydroxylase (TH)-positive nerves. We confirmed that the tissue content of NGF was lower in Snx25 mcKO mice than in wild-type mice, and in turn, dermal NGF injection restored tactile sensitivity in Snx25+/- mice and Snx25 mcKO mice to normal levels. These results indicate that CGRP-positive C-nociceptors (possibly also TH-positive C-LTMRs) associated dermal macrophages control tactile perception by producing NGF and secreting it into the dermis.

Keywords: Dermal macrophage; NGF; SNX25; Tactile perception.

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Dermis / metabolism
  • Macrophages* / metabolism
  • Male
  • Mice
  • Mice, Knockout*
  • Nerve Growth Factor* / metabolism
  • Signal Transduction*
  • Sorting Nexins* / genetics
  • Sorting Nexins* / metabolism
  • Touch Perception / physiology

Substances

  • Nerve Growth Factor
  • Sorting Nexins
  • Calcitonin Gene-Related Peptide