Centralization of noxious stimulus-induced analgesia (NSIA) is related to activity at inhibitory synapses in the spinal cord.
The duration of noxious stimulus-induced antinociception (NSIA) has been shown to outlast the pain stimulus that elicited it, however, the mechanism that determines the duration of analgesia is unknown. We evaluated the role of spinal excitatory and inhibitory receptors (NMDA, mGluR(5), mu-opioid, GABA(A), and GABA(B)), previously implicated in NSIA initiation, in its maintenance. As in our previous studies, the supraspinal trigeminal jaw-opening reflex (JOR) in the rat was used for nociceptive testing because of its remoteness from the region of drug application, the lumbar spinal cord. NSIA was reversed by antagonists for two inhibitory receptors (GABA(B) and mu-opioid) but not by antagonists for either of the two excitatory receptors (NMDA and mGluR(5)), indicating that NSIA is maintained by ongoing activity at inhibitory synapses in the spinal cord. Furthermore, spinal administration of the GABA(B) agonist baclofen mimicked NSIA in that it could be blocked by prior injection of the mu-opioid receptor antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) in nucleus accumbens. CTAP also blocked baclofen antinociception when administered in the spinal cord. We conclude that analgesia induced by noxious stimulation is maintained by activity in spinal inhibitory receptors.
Department of Oral and Maxillofacial Surgery, NIH Pain Center (UCSF), University of California at San Francisco, Rm C-522, Box 0440, San Francisco, CA 94143-0440, USA Department of Medicine, University of California, San Francisco, USA Faculty of Dentistry of Piracicaba, University of Campinas, Brazil.
Claudia H
CH
Tambeli
Jon D
JD
Levine
Robert W
RW
Gear
D000700:Analgesics / Q000037:antagonists & inhibitors; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002211:Capsaicin / Q000037:antagonists & inhibitors; D004347:Drug Interactions / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D018689:Sensory System Agents / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009292:Narcotic Antagonists; D010455:Peptides; D018080:Receptors, GABA-B; D017450:Receptors, Opioid, mu; D018689:Sensory System Agents; C009862:connective tissue-activating peptide; D001418:Baclofen; D002211:Capsaicin