Differential Effects of Glutamate Receptor Antagonists on Dorsal Horn Neurons Responding to Colorectal Distension in a Neonatal Colon Irritation Rat Model
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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 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.
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.
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