NMDA and quisqualate modulation of visceral nociception in the rat.
The effects of N-methyl-D-aspartic acid (NMDA; 100 fmol-1 nmol) or quisqualic acid (QA; 10 pmol-10 nmol) on visceromotor and pressor responses to noxious colorectal distention (CRD; 40 mmHg, 20 s duration, interstimulus interval: 4 min) were studied in awake rats. Lesser doses of NMDA (100 fmol-1 pmol) administered intrathecally (i.t.) to the lumbar spinal cord produced a dose-dependent facilitation of visceromotor as well as pressor responses to CRD (maximum with 1 pmol NMDA at 1 min). The greatest dose tested (1 nmol) attenuated these responses (maximum at 1 min) and also produced a caudally-directed biting and scratching behavior accompanied by vocalizations. NMDA did not produce any of the above effects when administered i.t. to the thoracic spinal cord. I.t. pretreatment with the NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (D-APV; 1 pmol), which produced no change in baseline activity or control responses, blocked all NMDA-produced effects in a reversible manner. QA produced dose-dependent inhibitory effects on visceromotor as well as pressor responses to noxious CRD when given i.t. to the lumbar spinal cord but not on administration to the thoracic spinal cord. Three nmol QA produced maximum inhibition at 2 min after administration and also produced caudally-directed biting and scratching. All of the QA-produced effects were reversibly blocked by i.t. pretreatment with the non-NMDA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX; 3 nmol), which produced no change in baseline activity or control responses. We also examined the effects of NMDA and QA on responses to graded intensities of CRD. One pmol NMDA selectively facilitated visceromotor responses to CRD at distention pressures of 40 and 80 mmHg but not at 20 mmHg. In contrast, 3 nmol QA inhibited visceromotor responses to CRD at all intensities tested. In summary, these data suggest that activation of NMDA and non-NMDA receptors in the spinal cord differentially modulates visceral nociceptive input. Spinal segmental NMDA receptor activation produces selective facilitation of visceral nociceptive processing at noxious intensities of stimulation and may thereby contribute to central mechanisms underlying visceral hyperalgesia.
Kolhekar
R
R
Department of Pharmacology, University of Iowa, Iowa City 52242.
Gebhart
G F
GF
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003106:Colon / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000503:physiopathology*
D011810:Quinoxalines; C056723:FG 9041; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid