Antinociception and inhibition from the periaqueductal gray are mediated in part by spinal 5-hydroxytryptamine(1A) receptors.
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.
Lin
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Department of Anatomy and Neuroscience and Marine Biomedical Institute, University of Texas Medical Branch, Galveston, USA.
Peng
Y B
YB
Willis
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WD
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D013997:Time Factors
D011985:Receptors, Serotonin; D009020:Morphine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011433:Propranolol