Distinct chemical classes of medium-sized transient receptor potential channel vanilloid 1-immunoreactive dorsal root ganglion neurons innervate the adult mouse jejunum and colon

Abstract

Physiological studies suggest visceral spinal afferents are generally small diameter, unmyelinated C-fibers or myelinated Adelta-fibers, but little is known about the size and chemical phenotypes of visceral sensory neurons supplying the small intestine. This study examines the size and expression patterns of transient receptor potential vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP), substance P (SP), neuronal nitric oxide synthase (NOS) and isolectin B4-binding (IB4) in dorsal root ganglion (DRG) neurons projecting to the gastrointestinal tract. The spinal afferent innervation of mouse jejunum and distal colon was investigated with retrograde neuronal tracing and multi-label immunohistochemistry. Expression of histochemical markers and soma sizes of retrogradely labeled DRG profiles were determined with confocal microscopy. Most (>75%) jejunal and colonic afferent neurons were medium- and large-sized cells. The majority (82%) of jejunal afferents expressed TRPV1, but few bound IB4. All retrogradely labeled jejunal afferents expressing NOS-immunoreactivity (64%) also expressed TRPV1 and CGRP and most expressed SP. Most labeled colonic afferents expressed TRPV1 (62%) and half expressed NOS. Taken together these data demonstrate that the spinal afferent supply of the jejunum and colon is largely from medium and large sensory neurons, suggesting most intestinal afferent axons are A fibers. The various chemically-defined subpopulations of afferents may play multiple roles in sensory innervation of the jejunum apart from nociceptive transduction. Additionally, we have identified a unique chemical code, TRPV1/NOS/CGRP/SP, that distinguishes many spinal afferent terminals from those of enteric neurons.