Differences in spinal distribution and neurochemical phenotype of colonic afferents in mouse and rat

Abstract

Visceral pain is a prevalent clinical problem and one of the most common ailments for which patients seek medical attention. Recent studies have described many of the physiological properties of visceral afferents, but not much is known regarding their anatomical characteristics. To determine the spinal distribution and neurochemical phenotype of colonic afferents in rodents, Alexa Fluor-conjugated cholera toxin-beta (CTB) was injected subserosally into the proximal and distal portions of the descending colon in Sprague Dawley rats and C57Bl/6 mice. Dorsal root ganglia (T10-S2) were processed for fluorescent immunohistochemistry and visualized by confocal microscopy. In the mouse, CTB-positive neurons were most numerous in the lumbosacral region (LS; L6-S1), with a smaller contribution in the thoracolumbar ganglia (TL; T13-L1). In contrast, CTB-positive neurons in the rat were most numerous in the TL ganglia, with a smaller contribution in the LS ganglia. The vast majority of CTB-positive neurons in both mouse and rat were positive for TRPV1 and CGRP and most likely unmyelinated, in that most colonic afferents were not positive for neurofilament heavy chain. In the mouse, the TL ganglia had a significantly higher percentage of TRPV1- and CGRP-positive neurons than did the LS ganglia, whereas no differences were observed in the rat. The high incidence of TRPV1-positive colonic afferents in rodents suggests that hypersensitivity from the viscera may be partially a TRPV1-mediated event, thereby providing a suitable target for the treatment of visceral pain.