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

Area of Science:

• Neuroscience
• Gastroenterology
• Visceral Pain Research

Background:

• The colorectum receives sensory input through distinct splanchnic and pelvic afferent nerve pathways.
• Understanding the central integration of these pathways is crucial for deciphering colorectal sensory-motor functions and visceral pain mechanisms.

Purpose of the Study:

• To identify the brainstem regions where sensory information from splanchnic and pelvic afferent nerves of the colorectum converges.
• To elucidate the specific roles of these afferent pathways in transmitting colorectal sensory information to the brain.

Main Methods:

• Utilized a transneuronal viral tracer (herpes simplex virus-1 H129-EGFP) injected into the distal colon to map ascending projections.
• Employed in vivo noxious colorectal distension (CRD) followed by brainstem immunolabeling for phosphorylated ERK (pERK) to identify activated neurons.
• Investigated the impact of dorsal root ganglia (DRG) removal of splanchnic and pelvic afferent neurons on CRD-evoked neuronal activation.

Main Results:

• Viral tracer revealed ascending input to medullary, pontine, and midbrain structures involved in sensory relay, pain modulation, and autonomic control.
• CRD activated neurons in brainstem areas that also received viral tracer labeling, confirming involvement in colorectal signaling.
• Removal of splanchnic DRG significantly reduced CRD-evoked activation in the caudal ventrolateral medulla, rostral ventromedial medulla, and lateral parabrachial nuclei.
• Removal of pelvic DRG significantly reduced CRD-evoked activation in the rostral ventromedial medulla, lateral parabrachial nuclei, locus coeruleus, Barrington's nucleus, and periaqueductal gray.

Conclusions:

• Splanchnic and pelvic afferent pathways from the colorectum project to distinct brainstem nuclei.
• These findings provide novel insights into the unique contributions of each pathway to the gut-brain axis.
• This research advances our understanding of colorectal sensory processing and its role in gut-brain communication.