Differential effects of glutamate receptor antagonists on dorsal horn neurons responding to colorectal distension in a neonatal colon irritation rat model.
OBJECTIVE
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 micromoL) 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 micromoL) had no significantly effect on the neuronal response to all intensities of CRD; however, CNQX (5 micromoL) significantly attenuated the responses to CRD in the 40-80 mmHg range. By contrast, CNQX (2-10 micromoL) significantly decreased the neuronal responses in CI rats to non-noxious and noxious CRD in a dose-dependent manner.


CONCLUSIONS
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.
Lin
Chun
C
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.
Al-Chaer
Elie D
ED
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002404:Catheterization; D003106:Colon / Q000294:innervation; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D008297:Male; D020671:Posterior Horn Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid