The NMDA receptor antagonist MK-801 attenuates c-Fos expression in the lumbosacral spinal cord following repetitive noxious and non-noxious colorectal distention.

The effects of pretreatment with an NMDA receptor antagonist, MK-801, on c-Fos (Fos) expression in the lumbosacral spinal cord following repetitive, noxious (80 mmHg) or non-noxious (20 mmHg) colorectal distention (CRD) was examined immunocytochemically in awake and urethane anesthetized rats. In awake rats, noxious CRD induced Fos expression in the lumbosacral spinal cord. Pretreatment with MK-801 (0.1-1.0 mg/kg, i.p.) produced no change or an increase in noxious CRD induced-Fos expression and caused aversive side effects. In order to examine greater doses of MK-801, further experiments were performed in rats anesthetized with urethane. Both noxious and non-noxious CRD induced Fos in the lumbosacral spinal cord. Pretreatment with MK-801 (0.5, 1.0, 5.0 mg/kg, i.p.) dose-dependently attenuated noxious CRD-induced Fos by 20-40%. Five mg/kg MK-801 attenuated non-noxious CRD-induced Fos by 20%. Lesser doses did not significantly attenuate Fos expression. The laminar distribution of Fos following MK-801 pretreatment revealed a tendency towards the deeper laminae showing the greatest attenuation at the highest dose of MK-801. Protein plasma extravasation in the colon measured with Evan's blue dye showed no difference between rats without balloons, rats with balloons that were not distended and non-noxious CRD. There was significantly more extravasation following noxious CRD. Pretreatment with systemic MK-801 had no effect on plasma extravasation produced by noxious CRD. These data suggest that the induction of Fos in the lumbosacral spinal cord by noxious and non-noxious CRD is partially NMDA receptor mediated. However, NMDA receptor activation contributes significantly more to noxious than non-noxious CRD-induced Fos. Inflammation of the colon following noxious CRD likely contributes to sensitization of colonic afferents which may contribute to the increased NMDA receptor-mediated Fos following the noxious stimulus.