Spinal NMDA receptors contribute to neuronal processing of acute noxious and nonnoxious colorectal stimulation in the rat

The present study investigated the role of NMDA receptors in the spinal pro cessing of acute noxious and nonnoxious colorectal stimulation using extrac ellular single-unit recording in the rat. Fifty-three neurons in the L-6-S- 2 dorsal horn of the spinal cord were studied. Neurons were identified usin g touch and light pinch of the ipsilateral perianal/scrotal area and colore ctal distention (CRD). All neurons had excitatory responses to CRD. Thirty neurons were studied using a search stimulus of 80-mmHg CRD. The effects of a systemically administered N-methyl-D-aspartate (NMDA) receptor channel b locker, dizocilpine maleate (MK-801) (0.1, 0.5, 1.0, and 5.0 mg/kg), were t ested on the CRD-evoked responses of 13 neurons. The lowest dose had no eff ect on the neuronal responses to CRD, while greater doses lowered the CRD-e voked responses at all distention pressures tested (20, 40, 60, and 80 mmHg ). Similarly, spinal application of MK-801 (20, 50, 100, and 200 nmol) atte nuated CRD-evoked activity (n=9). In addition, a spinally administered comp etitive NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV) (30 , 60, 120, and 240 nmol), dose-dependently attenuated the CRD-evoked respon se at all distention pressures (n=5). Systemically administered APV did not affect neuronal responses to CRD (n=3). Twenty-three neurons were studied in animals that never received distention pressures exceeding 30 mmHg; the search stimulus ranged between 20- and 30-mmHg CRD. These neurons were test ed using 20-mmHg CRD. Systemically administered MK-801 facilitated the resp onse to 20-mmHg CRD in three neurons and inhibited the response in five neu rons, and the response of five neurons was not affected. Spinally administe red MK-801 had no effect on neuronal responses to 20-mmHg CRD in six neuron s. However, spinally administered APV dose-dependently decreased the respon se to 20-mmHg CRD in four neurons. These results are consistent with our pr evious observations that used Fos expression as the index, suggesting that spinal NMDA receptors contribute to processing of both noxious and nonnoxio us CRD.