Identification of the Visceral Pain Pathway Activated by Noxious Colorectal Distension in Mice

Department of Human Physiology, Flinders Medical Science and Technology Cluster, Flinders University Adelaide, SA, Australia.
Frontiers in Neuroscience (Impact Factor: 3.66). 02/2011; 5:16. DOI: 10.3389/fnins.2011.00016
Source: PubMed


In patients with irritable bowel syndrome (IBS), visceral pain is evoked more readily following distension of the colorectum. However, the identity of extrinsic afferent nerve pathway that detects and transmits visceral pain from the colorectum to the spinal cord is unclear. In this study, we identified which extrinsic nerve pathway(s) underlies nociception from the colorectum to the spinal cord of rodents. Electromyogram (EMG) recordings were made from the transverse oblique abdominal muscles in anesthetized wild type (C57BL/6) mice and acute noxious intraluminal distension (100-120 mmHg) applied to the terminal 15mm of rectum to activate visceromotor responses (VMRs). Cutting the lumbar colonic nerves in vivo had no detectable effect on the VMRs evoked by colorectal distension. Lesioning right or left hypogastric nerves also failed to reduce VMRs. However, lesioning left and right branches of the rectal nerves completely abolished the VMRs, regardless of whether the lumbar colonic or hypogastric nerves were severed. Electrical stimulation applied to either the lumbar colonic or hypogastric nerves in vivo, failed to elicit a VMR. In contrast, electrical stimulation (2-5Hz, 0.4ms, 60V) applied to the rectum reliably elicited VMRs, which were abolished by selective lesioning of the rectal nerves. DiI retrograde labelling from the colorectum labelled sensory neurons only in dorsal root ganglia (DRG) of the lumbosacral region of the spinal cord. In contrast, injection of DiI into the mid to proximal colon labelled sensory neurons in DRG primarily of the lower thoracic level (T8-L4) of the spinal cord. The visceral pain pathway activated by acute noxious distension of the terminal 15 mm of mouse rectum is transmitted predominantly, if not solely, through rectal/pelvic afferent nerve fibres to the spinal cord. The sensory neurons of this spinal afferent pathway lie in the lumbosacral region of the spinal cord, primarily at the level of S2 and S3.

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    • "In the GI tract, extensive evidence has now been presented that noxious and innocuous stimuli from the GI-tract are detected and transmitted by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRG), but whose nerve endings lie within the wall of the GI-tract (Traub, 2000; Kyloh et al., 2011; Zagorodnyuk et al., 2011). Whilst much has been learnt from extracellular recordings of spinal afferents that lie outside the gut wall, this technique does not reveal direct information about the mechanisms underlying sensory transduction, since this process only occurs within the afferent nerve endings located within the peripheral organ. "
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