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Identification of the visceral pain pathway activated by noxious colorectal distension in mice.

Kyloh M, Nicholas S, Zagorodnyuk VP, Brookes SJ, Spencer NJ - Front Neurosci (2011)

Bottom Line: Also, lesions applied to the right or left hypogastric nerves failed to reduce VMRs.Electrical stimulation applied to either the lumbar colonic or hypogastric nerves in vivo, failed to elicit a VMR.The sensory neurons of this spinal afferent pathway lie primarily in the lumbosacral region of the spinal cord, between L6 and S1.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Physiology, Flinders Medical Science and Technology Cluster, Flinders University Adelaide, SA, Australia.

ABSTRACT
In patients with irritable bowel syndrome, 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 recordings were made from the transverse oblique abdominal muscles in anesthetized wild type (C57BL/6) mice and acute noxious intraluminal distension stimuli (100-120 mmHg) were applied to the terminal 15 mm of colorectum to activate visceromotor responses (VMRs). Lesioning the lumbar colonic nerves in vivo had no detectable effect on the VMRs evoked by colorectal distension. Also, lesions applied to the right or left hypogastric nerves failed to reduce VMRs. However, lesions applied to both left and right branches of the rectal nerves abolished 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 (2-5 Hz, 0.4 ms, 60 V) applied to the rectum reliably elicited VMRs, which were abolished by selective lesioning of the rectal nerves. DiI retrograde labeling from the colorectum (injection sites 9-15 mm from the anus, measured in unstretched preparations) labeled sensory neurons primarily in dorsal root ganglia (DRG) of the lumbosacral region of the spinal cord (L6-S1). In contrast, injection of DiI into the mid to proximal colon (injection sites 30-75 mm from the anus, measured in unstretched preparations) labeled sensory neurons in DRG primarily of the lower thoracic level (T6-L2) of the spinal cord. The visceral pain pathway activated by acute noxious distension of the terminal 15 mm of mouse colorectum is transmitted predominantly, if not solely, through rectal/pelvic afferent nerve fibers to the spinal cord. The sensory neurons of this spinal afferent pathway lie primarily in the lumbosacral region of the spinal cord, between L6 and S1.

No MeSH data available.


Related in: MedlinePlus

Identification of the pain pathway underlying activation of the visceromotor responses to colorectal distension. (A) Diagrammatic representation of the major extrinsic nerve trunks that lie between the rectum and spinal cord. (B) Control visceromotor responses elicited by acute noxious colorectal distension. (C) Cutting only the lumbar colonic nerves did not reduced the VMRs to acute noxious colorectal distension. (D) Similar lesions applied to the hypogastric nerves also did not reduce the VMRs. (E) However, cutting of the rectal nerves abolished the visceromotor responses. (F) Shows the mean grouped data of VMRs evoked by acute noxious colorectal distension after lesions applied to the lumbar colonic, hypogastric, and rectal nerve trunks from N = 5 animals. * Refers to significantdifference (P < 0.05).
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Figure 1: Identification of the pain pathway underlying activation of the visceromotor responses to colorectal distension. (A) Diagrammatic representation of the major extrinsic nerve trunks that lie between the rectum and spinal cord. (B) Control visceromotor responses elicited by acute noxious colorectal distension. (C) Cutting only the lumbar colonic nerves did not reduced the VMRs to acute noxious colorectal distension. (D) Similar lesions applied to the hypogastric nerves also did not reduce the VMRs. (E) However, cutting of the rectal nerves abolished the visceromotor responses. (F) Shows the mean grouped data of VMRs evoked by acute noxious colorectal distension after lesions applied to the lumbar colonic, hypogastric, and rectal nerve trunks from N = 5 animals. * Refers to significantdifference (P < 0.05).

Mentions: For experiments in which lesions were made to each of the major spinal nerve pathways, it was important to be able to visualize these nerves in vivo. Once mice had been fully anesthetized, a midline laparotomy was made to expose the internal organs. The small intestine and cecum were gently removed from the abdominal cavity, whilst retaining continuity with the vascular and nervous supplies. A fine cotton thread was looped around the distal colon at the junction of the inferior mesenteric artery (IMA) and colon. This thread was then raised vertically, such that the distal colon was separated from the abdominal aorta by a space of approximately 3–4 mm. This allowed sufficient space to place fine transmural stimulating wires across the IMA and all the LCN. It also allowed sufficient space to allow the LCN to be severed with ultra fine surgical dissecting scissors. To access the hypogastric nerves, the junction between the abdominal aorta and left and right iliac arteries was identified (see Figure 1; Miller and Szurszewski, 1994). The hypogastric nerves lie directly above (dorsal) to the left and right iliac arteries. This allowed clear visualization of the hypogastric nerves to facilitate lesions of the nerves, or allow direct access to stimulation by fine transmural electrical stimulation. To directly stimulate the hypogastric nerves using electrical stimulation, a fine 8/0 suture thread was looped underneath each branch of the hypogastric nerves so that the nerve trunk was geographically separated from the iliac artery. This allowed transmural electrical stimulating wires to be placed around the nerve and not apply electrical stimuli to the iliac arteries themselves. To lesion the rectal nerves, a small incision was made through the skin caudal to the pelvic bone. The rectum was exposed and fine rectal nerves visualized. Once visualized, fine surgical scissors were used to lesion all rectal nerves between the anus and IMA.


Identification of the visceral pain pathway activated by noxious colorectal distension in mice.

Kyloh M, Nicholas S, Zagorodnyuk VP, Brookes SJ, Spencer NJ - Front Neurosci (2011)

Identification of the pain pathway underlying activation of the visceromotor responses to colorectal distension. (A) Diagrammatic representation of the major extrinsic nerve trunks that lie between the rectum and spinal cord. (B) Control visceromotor responses elicited by acute noxious colorectal distension. (C) Cutting only the lumbar colonic nerves did not reduced the VMRs to acute noxious colorectal distension. (D) Similar lesions applied to the hypogastric nerves also did not reduce the VMRs. (E) However, cutting of the rectal nerves abolished the visceromotor responses. (F) Shows the mean grouped data of VMRs evoked by acute noxious colorectal distension after lesions applied to the lumbar colonic, hypogastric, and rectal nerve trunks from N = 5 animals. * Refers to significantdifference (P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3046361&req=5

Figure 1: Identification of the pain pathway underlying activation of the visceromotor responses to colorectal distension. (A) Diagrammatic representation of the major extrinsic nerve trunks that lie between the rectum and spinal cord. (B) Control visceromotor responses elicited by acute noxious colorectal distension. (C) Cutting only the lumbar colonic nerves did not reduced the VMRs to acute noxious colorectal distension. (D) Similar lesions applied to the hypogastric nerves also did not reduce the VMRs. (E) However, cutting of the rectal nerves abolished the visceromotor responses. (F) Shows the mean grouped data of VMRs evoked by acute noxious colorectal distension after lesions applied to the lumbar colonic, hypogastric, and rectal nerve trunks from N = 5 animals. * Refers to significantdifference (P < 0.05).
Mentions: For experiments in which lesions were made to each of the major spinal nerve pathways, it was important to be able to visualize these nerves in vivo. Once mice had been fully anesthetized, a midline laparotomy was made to expose the internal organs. The small intestine and cecum were gently removed from the abdominal cavity, whilst retaining continuity with the vascular and nervous supplies. A fine cotton thread was looped around the distal colon at the junction of the inferior mesenteric artery (IMA) and colon. This thread was then raised vertically, such that the distal colon was separated from the abdominal aorta by a space of approximately 3–4 mm. This allowed sufficient space to place fine transmural stimulating wires across the IMA and all the LCN. It also allowed sufficient space to allow the LCN to be severed with ultra fine surgical dissecting scissors. To access the hypogastric nerves, the junction between the abdominal aorta and left and right iliac arteries was identified (see Figure 1; Miller and Szurszewski, 1994). The hypogastric nerves lie directly above (dorsal) to the left and right iliac arteries. This allowed clear visualization of the hypogastric nerves to facilitate lesions of the nerves, or allow direct access to stimulation by fine transmural electrical stimulation. To directly stimulate the hypogastric nerves using electrical stimulation, a fine 8/0 suture thread was looped underneath each branch of the hypogastric nerves so that the nerve trunk was geographically separated from the iliac artery. This allowed transmural electrical stimulating wires to be placed around the nerve and not apply electrical stimuli to the iliac arteries themselves. To lesion the rectal nerves, a small incision was made through the skin caudal to the pelvic bone. The rectum was exposed and fine rectal nerves visualized. Once visualized, fine surgical scissors were used to lesion all rectal nerves between the anus and IMA.

Bottom Line: Also, lesions applied to the right or left hypogastric nerves failed to reduce VMRs.Electrical stimulation applied to either the lumbar colonic or hypogastric nerves in vivo, failed to elicit a VMR.The sensory neurons of this spinal afferent pathway lie primarily in the lumbosacral region of the spinal cord, between L6 and S1.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Physiology, Flinders Medical Science and Technology Cluster, Flinders University Adelaide, SA, Australia.

ABSTRACT
In patients with irritable bowel syndrome, 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 recordings were made from the transverse oblique abdominal muscles in anesthetized wild type (C57BL/6) mice and acute noxious intraluminal distension stimuli (100-120 mmHg) were applied to the terminal 15 mm of colorectum to activate visceromotor responses (VMRs). Lesioning the lumbar colonic nerves in vivo had no detectable effect on the VMRs evoked by colorectal distension. Also, lesions applied to the right or left hypogastric nerves failed to reduce VMRs. However, lesions applied to both left and right branches of the rectal nerves abolished 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 (2-5 Hz, 0.4 ms, 60 V) applied to the rectum reliably elicited VMRs, which were abolished by selective lesioning of the rectal nerves. DiI retrograde labeling from the colorectum (injection sites 9-15 mm from the anus, measured in unstretched preparations) labeled sensory neurons primarily in dorsal root ganglia (DRG) of the lumbosacral region of the spinal cord (L6-S1). In contrast, injection of DiI into the mid to proximal colon (injection sites 30-75 mm from the anus, measured in unstretched preparations) labeled sensory neurons in DRG primarily of the lower thoracic level (T6-L2) of the spinal cord. The visceral pain pathway activated by acute noxious distension of the terminal 15 mm of mouse colorectum is transmitted predominantly, if not solely, through rectal/pelvic afferent nerve fibers to the spinal cord. The sensory neurons of this spinal afferent pathway lie primarily in the lumbosacral region of the spinal cord, between L6 and S1.

No MeSH data available.


Related in: MedlinePlus