Antinociception and inhibition from the periaqueductal gray are mediated in part by spinal 5-hydroxytryptamine(1A) receptors

Q Lin, YB Peng and WD Willis

Department of Anatomy and Neuroscience and Marine Biomedical Institute, University of Texas Medical Branch, Galveston, USA.

Although 5-hydroxytryptamine (5-HT) is known to be involved in the mediation of antinociception from the periaqueductal gray (PAG), its mode of action remains obscure. This investigation uses selective 5- HT(1A) receptor agonist and antagonist drugs in both behavioral and electrophysiological studies on antinociceptive mechanisms of the PAG of rats. Intraspinal administration of 8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT), a selective 5-HT(1A) agonist, by microdialysis produced a dose-dependent antinociception in the radiant- heat paw withdrawal test. Dorsal horn neuronal activity was recorded extracellularly to test responses to noxious cutaneous stimuli when 8- OH-DPAT was administered iontophoretically, and it was observed that the noxious-evoked responses were inhibited in a current-related manner in all cells examined. The inhibitory effects elicited by 8-OH-DPAT could be selectively blocked by perfusion of the spinal cord with S-(-- )-propranolol, a selective 5-HT(1A) antagonist. The antinociception produced by microinjection of morphine into the PAG was significantly attenuated in a dose-related manner by S-(--)-propranolol administered into the spinal cord. Similarly, the inhibition of dorsal horn neuronal responses to cutaneous mechanical stimuli produced by electrical stimulation in the PAG was reduced by S-(--)-propranolol administered into the spinal cord in the majority of cells tested. These data suggest that the release of 5-HT in the dorsal horn by stimulation in the PAG may act directly on spinal 5-HT(1A) receptors, resulting in inhibition of dorsal horn neurons. This is presumably one of the antinociceptive mechanisms of the descending serotonergic inhibitory pathway.

Volume 276, Issue 3, pp. 958-967, 03/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				G.-D. Chen, H.-Y. Peng, K.-C. Tung, C.-L. Cheng, Y.-J. Chen, J.-M. Liao, Y.-C. Ho, S.-F. Pan, M.-J. Chen, and T.-B. Lin Descending facilitation of spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1115 - F1122. [Abstract] [Full Text] [PDF]

				L. Bardin, M.-B. Assie, M. Pelissou, I. Royer-Urios, A. Newman-Tancredi, J.-P. Ribet, F. Sautel, W. Koek, and F. C. Colpaert Dual, Hyperalgesic, and Analgesic Effects of the High-Efficacy 5-Hydroxytryptamine 1A (5-HT1A) Agonist F 13640 [(3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl}piperidin-1-yl]methanone, Fumaric Acid Salt]: Relationship with 5-HT1A Receptor Occupancy and Kinetic Parameters J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1034 - 1042. [Abstract] [Full Text] [PDF]

				M. A. Oatway, Y. Chen, J. C. Bruce, G. A. Dekaban, and L. C. Weaver Anti-CD11d Integrin Antibody Treatment Restores Normal Serotonergic Projections to the Dorsal, Intermediate, and Ventral Horns of the Injured Spinal Cord J. Neurosci., January 19, 2005; 25(3): 637 - 647. [Abstract] [Full Text] [PDF]

				Y. B. Peng, J. Wu, W. D. Willis, and D. R. Kenshalo GABAA and 5-HT3 Receptors Are Involved in Dorsal Root Reflexes: Possible Role in Periaqueductal Gray Descending Inhibition J Neurophysiol, July 1, 2001; 86(1): 49 - 58. [Abstract] [Full Text] [PDF]

				H. Kakizaki, M. Yoshiyama, T. Koyanagi, and W. C. De Groat Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition-reflex pathway in the rat Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2001; 280(5): R1407 - R1413. [Abstract] [Full Text] [PDF]

				M. Cui, Y. Feng, D. J. McAdoo, and W. D. Willis Periaqueductal Gray Stimulation-Induced Inhibition of Nociceptive Dorsal Horn Neurons in Rats Is Associated with the Release of Norepinephrine, Serotonin, and Amino Acids J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 868 - 876. [Abstract] [Full Text]