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 processing of acute noxious and nonnoxious colorectal stimulation using extracellular single-unit recording in the rat. Fifty-three neurons in the L6-S2 dorsal horn of the spinal cord were studied. Neurons were identified using touch and light pinch of the ipsilateral perianal/scrotal area and colorectal 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 blocker, dizocilpine maleate (MK-801) (0.1, 0.5, 1.0, and 5.0 mg/kg), were tested on the CRD-evoked responses of 13 neurons. The lowest dose had no effect on the neuronal responses to CRD, while greater doses lowered the CRD-evoked responses at all distention pressures tested (20, 40, 60, and 80 mmHg). Similarly, spinal application of MK-801 (20, 50, 100, and 200 nmol) attenuated CRD-evoked activity (n = 9). In addition, a spinally administered competitive NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV) (30, 60, 120, and 240 nmol), dose-dependently attenuated the CRD-evoked response 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 tested using 20-mmHg CRD. Systemically administered MK-801 facilitated the response to 20-mmHg CRD in three neurons and inhibited the response in five neurons, and the response of five neurons was not affected. Spinally administered MK-801 had no effect on neuronal responses to 20-mmHg CRD in six neurons. However, spinally administered APV dose-dependently decreased the response to 20-mmHg CRD in four neurons. These results are consistent with our previous observations that used Fos expression as the index, suggesting that spinal NMDA receptors contribute to processing of both noxious and nonnoxious CRD.
Ji
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Department of Oral and Craniofacial Biological Sciences, Dental School, University of Maryland, Baltimore, Maryland 21201, USA.
Traub
R J
RJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002404:Catheterization; D003106:Colon / Q000294:innervation*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012007:Rectum / Q000294:innervation*; D013116:Spinal Cord / Q000166:cytology*; D017833:Visceral Afferents / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate