Nociception originating from the crural fascia in rats

Peripheral mechanisms of fascial nociception and spinal projections were revealed, strengthening the supposition that the muscle fascia is a nociceptive sensory tissue/organ. Little is documented in the literature as to the function of muscle fascia in nociception and pain. The aim of this study was to examine the distribution of presumptive nociceptive nerve fibers, to characterize fascial thin-fiber sensory receptors, and to examine the spinal projection of nociceptive input from the rat crural fascia (CF). Nerve fibers labeled with specific antibodies to calcitonin gene-related peptide (CGRP) and peripherin were found to be densely distributed in the distal third of the CF. Thin-fiber receptors (Aδ- and C-fibers) responding to pinching stimuli to the CF with sharpened watchmaker’s forceps, identified in vivo with the teased fiber technique from the common peroneal nerve, exist in the CF. Forty-three percent of the mechano-responsive fascial C-fibers were polymodal receptors (nociceptors) responding to mechanical, chemical (bradykinin), and heat stimuli, whereas almost all Aδ-fibers were responsive only to mechanical stimuli. Repetitive pinching stimulus to the CF induced c-Fos protein expression in the middle to medial part of superficial layers ie, laminae I–II of the spinal dorsal horn at segments L2 to L4, peaking at L3. These results clearly demonstrate the following: 1) peptidergic and non-peptidergic axons of unmyelinated C-fibers with nerve terminals are distributed in the CF; 2) peripheral afferents responding to noxious stimuli exist in the fascia, and 3) nociceptive information from the CF is mainly processed in the spinal dorsal horn at the segments L2 to L4. These results together indicate that the “muscle fascia,” a tissue often overlooked in pain research, can be an important source of nociception under normal conditions.