Splanchnic and Pelvic Spinal Afferent Pathways Relay Sensory Information From the Mouse Colorectum Into Distinct Brainstem Circuits

The distal colon and rectum (colorectum) are innervated by two distinct spinal (splanchnic and pelvic) afferent nerve pathways. This study aimed to identify where the sensory information relayed by splanchnic and pelvic afferents integrates within the brainstem. Microinjection of transneuronal viral tracer (herpes simplex virus-1 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 h and in the pontine and caudal midbrain at 120 h after inoculation. In a separate cohort of mice, in vivo noxious colorectal distension (CRD) followed by brainstem immunolabeling for phosphorylated MAP kinase ERK 1/2 (pERK) determined neurons activated by CRD. Many of the structures containing H129-EGFP+ labeling also contained pERK-labeled neurons, indicating H129-EGFP+ labeling in colorectal signaling pathways. Surgical removal of dorsal root ganglia (DRG) containing the cell bodies of splanchnic colorectal afferent neurons significantly reduced CRD-evoked pERK neuronal activation within the caudal ventrolateral medulla, rostral ventromedial medulla, and the lateral parabrachial nuclei. Surgical removal of the DRG containing the cell bodies of pelvic colorectal afferent neurons significantly reduced CRD-evoked pERK neuronal activation within the rostral ventromedial medulla, lateral parabrachial nuclei, the locus coeruleus, Barrington's nucleus, and periaqueductal gray. Collectively, this study showed that the two spinal afferent pathways innervating the colorectum relay information into different brainstem structures and provide new insight into their unique roles in relaying information into the gut-brain axis controlling colorectal sensory-motor function.