Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2005; 11(41): 6495-6502
Published online Nov 7, 2005. doi: 10.3748/wjg.v11.i41.6495
Differential effects of glutamate receptor antagonists on dorsal horn neurons responding to colorectal distension in a neonatal colon irritation rat model
Chun Lin, Elie D Al-Chaer
Chun Lin, Elie D Al-Chaer, Laboratory of Elie D Al-Chaer (ACELAB), Center for Pain Research (CPR), University of Texas Medical Branch, Galveston, TX 77555-0632, United States
Chun Lin, Center for Neubiological Research, Department of Physiology and Pathophysiology, Fujian Medical University, Fuzhou 350004, Fujian Province, China
Author contributions: All authors contributed equally to the work.
Supported by NIH grant 40434
Correspondence to: Elie D Al-Chaer, MS, Ph D, JD, Associate Professor of Pediatrics, Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham, Slot 842, Little Rock, AR 72205-842, United States. ealchaer@uams.edu
Telephone: +1-501- 526-7828 Fax: +1-501- 526-7862
Received: May 10, 2005
Revised: June 15, 2005
Accepted: June 18, 2005
Published online: November 7, 2005
Abstract

AIM: To investigate and compare the effects of spinal D-(-)-2-amino-7-phosphonoheptanoic acid (AP-7) and 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX), two glutamate receptor antagonists, on the responses of dorsal horn neurons to colorectal distension (CRD) in adult rats exposed to neonatal colon irritation (CI).

METHODS: Hypersensitive SD rats were generated by CI during postnatal days 8, 10 and 12. Experiments on adult rats were performed using extracellular single-unit recording. The effects of spinal application of AP-7 (0.001, 0.01, 0.1, 1 mmoL) were tested on the CRD-evoked neuronal responses in 16 controls and 17 CI rats. The effects of CNQX (0.2, 2, 5, 10 μmoL) were also tested on the CRD-evoked responses of 17 controls and 18 CI neurons.

RESULTS: (1) The average responses of lumbosacral neurons to all intensities of CRD in CI rats were significantly higher than those in control rats; (2) In control rats, AP-7（0.01 mmoL）had no significant effect on the neuronal response to all intensities of CRD (20, 40, 60, 80 mmHg); while AP-7 (0.1 mmoL) inhibited the neuronal response to 80-mmHg CRD. By contrast, in CI rats, AP-7 (0.01-1 mmoL) attenuated the CRD-evoked neuronal responses to all distention pressures in a dose-dependent manner; (3) In control rats, CNQX (2 μmoL) had no significantly effect on the neuronal response to all intensities of CRD; however, CNQX (5 μmoL) significantly attenuated the responses to CRD in the 40-80 mmHg range. By contrast, CNQX (2-10 μmoL) significantly decreased the neuronal responses in CI rats to non-noxious and noxious CRD in a dose-dependent manner.

CONCLUSION: Our results suggest that spinal N-methyl-D-aspartate (NMDA) and non-NMDA receptors may contribute to the processing of central sensitivity in a neonatal CI rat model, but they may play different roles in it.

Keywords: Chronic visceral hypersensitivity, Dorsal horn neurons, Irritable bowel syndrome, NMDA receptors, Non-NMDA receptors