Sensory nerve fibers containing calcitonin gene-related peptide in gastrocnemius, latissimus dorsi and erector spinae muscles and thoracolumbar fascia in mice

- 75-90% of axons in mouse skeletal muscles contained CGRP and a third of these did not contain SP.
- Retrograde tracing confirmed two distinct populations of CGRP immunoreactive neurons supply muscle.
- These populations were in similar proportions in back muscles and thoracolumbar fascia.
- Innervation density was three times higher in the thoracolumbar fascia than back muscles.
- Non-peptidergic nerve fibers were less prevalent in back muscles than gastrocnemius.

Chronic pain is a significant burden and much is attributed to back muscles. Back muscles and their associated fasciae make important and distinct contributions to back pain. Peptidergic nociceptors innervating these structures contribute to central transmission and pain modulation by peripheral and central actions. Plastic changes that augment and prolong pain are exhibited by neurons containing calcitonin gene-related peptide (CGRP) following muscle injury. Subpopulations of neurons containing this peptide have been identified in dorsal root ganglia but the distribution of their fibers in skeletal muscles and associated fasciae has not been fully documented. This study used multiple-labeling immunofluorescence and retrograde axonal tracing to identify dorsal root ganglion cells associated with muscle, and to characterize the distribution and density of their nerve fibers in mouse gastrocnemius and back muscles and in the thoracolumbar fascia. Most nerve fibers in these tissues contained CGRP and two major subpopulations of neurons were found: those containing CGRP and substance P (SP) and those containing CGRP but not SP. Innervation density was three times higher in the thoracolumbar fascia than in muscles of the back. These studies show mouse back and leg muscles are predominantly innervated by neurons containing CGRP, an important modulator of pain signal transmission. There are two distinct populations of neurons containing this peptide and their fibers were three times more densely distributed in the thoracolumbar fascia than back muscles.