Elsevier

Journal of Pediatric Surgery

Volume 36, Issue 11, November 2001, Pages 1679-1684
Journal of Pediatric Surgery

Novel capsaicin (VR1) and purinergic (P2X3) receptors in Hirschsprung's intestine

Presented at the 34th Annual Meeting of the Pacific Association of Pediatric Surgeons, Kyoto, Japan, April 4-8, 2001.
https://doi.org/10.1053/jpsu.2001.27959Get rights and content

Abstract

Background/Purpose: Studies of Hirschsprung's disease (HSCR) have shown that hypertrophic nerves in aganglionic bowel are mainly of extrinsic origin and may contain sensory elements. Recent advances have shown a specific capsaicin receptor VR1 (vanilloid receptor-1), and an ATP-gated ion channel P2X3, which are expressed by sensory neurons. Methods: This study investigated, for the first time, the distribution of VR1- and P2X3-immunoreactivity in normal adult, infant, and HSCR large intestine, using specific antibodies for immunohistochemistry. Results: VR1-immunoreactive fibers and nerve fascicles, but not somata, were detected in all regions of the bowel in controls with few weakly immunostained fibers in the mucosa/lamina propria. Hypertrophic nerve bundles in hypoganglionic and aganglionic bowel showed intense VR1-immunoreactivity, whereas normoganglionic regions of HSCR were similar to controls. P2X3-immunoreactive neuronal cell bodies, in some instances with long axonal processes, were detected in the myenteric and submucous plexuses in control infant, adult, and ganglionic HSCR samples. Aganglionic samples showed weak P2X3-immunoreactivity in hypertrophic nerve fasciculi in the submucous and myenteric plexuses. Conclusions: The presence of VR1- and P2X3-immunoreactivities in aganglionic HSCR bowel indicates that sensory nerves may form a significant proportion of its hypertrophic innervation. The functional significance of P2X3 and VR1 receptors in enteric nerves deserves further investigation. J Pediatr Surg 36:1679-1684. Copyright © 2001 by W.B. Saunders Company.

Section snippets

HSCR and control patients

Full-thickness, surgically resected colonic tissues were obtained from 8 patients with approval from the local ethics committee. All patients had sporadic distal colonic or short-segment-disease without clinical evidence of an established major genetic syndrome, eg, Down's syndrome/Shah-Waardenburg syndrome (6 male, 2 female, age 0.2 to 1.0 years). Specimens were taken from aganglionic and normoganglionic regions on the basis of histologic characterization. Age-matched control tissues were

VR1

In control tissues, VR1 immunoreactivity was detected in nerve fascicles in the myenteric plexus with fibers in the muscle layers (Fig 1a).

. VR1-immunoreactive nerve fibers/fasciculi in (a) the submucosa of normal adult intestine with some fibers in the adjacent circular muscle layer (arrow), (b) submucosa of control infant intestine with fibers penetrating adjacent muscularis mucosae (arrow). Greatly enlarged, hypertrophic, VR1-immunoreactive nerve fibres/fasciculi in Hirschsprung's diseased (c)

Discussion

The basic neural reflex circuit for normal peristalsis consists of sensory neurons, interneurons and motor neurons. Afferent nerves carry impulses generated by bowel wall distension and chemical or mechanical irritation of bowel mucosa to activate interneurons that stimulate motor excitatory neurons proximally and inhibitory neurons distally.16 VR1 and P2X3 are novel receptors of subsets of nociceptive sensory neurons. Our finding of VR1-and P2X3-immunoreactive nerves in the myenteric and

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    Address reprint requests to Professor Praveen Anand, Peripheral Neuropathy Unit, Imperial College School of Medicine, Hammersmith Hospital, London, England, or Professor Paul K.H. Tam, Department of Surgery, University of Hong Kong Medical Center, Queen Mary Hospital, Hong Kong SAR, China.

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