Splanchnic and pelvic spinal afferent pathways relay sensory information from the mouse colorectum into distinct brainstem circuits.

Abstract

This study aimed to identify where the sensory information relayed by the two spinal afferent pathways innervating the distal colon and rectum (colorectum), the splanchnic and pelvic spinal afferent pathways, integrates within the brainstem. Localised injections of transneuronal viral tracer (herpes simplex virus H129 strain expressing EGFP (H129-EGFP)) into the distal colon was used to assess the brainstem structures receiving ascending input from the colorectum. H129-EGFP+ cells were distributed in structures involved in ascending sensory relay, descending pain modulation and autonomic regulation in the medulla from 96 hours and in pontine and caudal midbrain 120 hours after inoculation. In a separate cohort of mice, in vivo noxious colorectal distension (CRD) followed by brainstem immunolabelling for phosphorylated MAP kinase ERK 1/2 (pERK) showed that many of the structures in which H129-EGFP+ labelling was observed were relevant to colorectal sensory processing. Surgical removal of dorsal root ganglia (DRG) containing cell bodies of splanchnic colorectal afferent neurons, significantly reduced CRD evoked neuronal activation within the caudal ventrolateral medulla, rostral ventromedial medulla and the lateral parabrachial nuclei. Whilst, removal of DRG containing cell bodies of pelvic colorectal afferent neurons significantly reduced CRD evoked neuronal activation within the rostral ventromedial medulla, lateral parabrachial nuclei, the locus coeruleus, Barringtons nucleus and periaqueductal gray. Collectively, this study showed that the two spinal afferent pathways innervating the colorectum differentially shape colorectal processing within the brainstem and provides new insight into their unique roles to mediating visceromotor responses and defecation associated with colorectal nociception.