Comparative localization of colorectal sensory afferent central projections in the mouse spinal cord dorsal horn and caudal medulla dorsal vagal complex

The distal colon and rectum (colorectum) are innervated by spinal and vagal afferent pathways. The central circuits into which vagal and spinal afferents relay colorectal nociceptive information remain to be comparatively assessed. To address this, regional colorectal retrograde tracing and colorectal distension (CRD)-evoked neuronal activation were used to compare the circuits within the dorsal vagal complex (DVC) and dorsal horn (thoracolumbar [TL] and lumbosacral [LS] spinal levels) into which vagal and spinal colorectal afferents project. Vagal afferent projections were observed in the nucleus tractus solitarius (NTS), area postrema (AP), and dorsal motor nucleus of the vagus (DMV), labeled from the rostral colorectum. In the NTS, projections were opposed to catecholamine and pontine parabrachial nuclei (PbN)-projecting neurons. Spinal afferent projections were labeled from rostral through to caudal aspects of the colorectum. In the dorsal horn, the number of neurons activated by CRD was linked to pressure intensity, unlike in the DVC. In the NTS, 13% +/- 0.6% of CRD-activated neurons projected to the PbN. In the dorsal horn, at the TL spinal level, afferent input was associated with PbN-projecting neurons in lamina I (LI), with 63% +/- 3.15% of CRD-activated neurons in LI projecting to the PbN. On the other hand, at the LS spinal level, only 18% +/- 0.6% of CRD-activated neurons in LI projected to the PbN. The collective data identify differences in the central neuroanatomy that support the disparate roles of vagal and spinal afferent signaling in the facilitation and modulation of colorectal nociceptive responses. This study used (i) retrograde tracing from different regions of the colorectum and (ii) in vivo colorectal distension, at nonnoxious and noxious pressures, combined with (iii) retrograde tracing from the pontine parabrachial nuclei (PbN) to (a) localize the central projections of colorectal spinal and vagal afferent neurons, (b) compare the relative amounts of neuronal activation evoked by CRD between vagal and spinal pathways, and (c) identify sites of nociceptive processing and sensory-motor integration within the (iv) caudal medulla dorsal vagal complex (DVC), (v) thoracolumbar dorsal horn, and (vi) lumbosacral dorsal horn into which vagal and spinal afferents relay. The data provide new insights into the central neuroanatomy that shapes the comparative roles of vagal and spinal afferent pathways to colorectal pain-evoked visceromotor responses in the mouse. image