Role of spinal serotonin1 receptor subtypes in thermally and mechanically elicited nociceptive reflexes.
The ability of 5-HT1A and 5-HT1B agonists to alter a spinal animal's nociceptive threshold was examined using two analgesiometric tests. In the spinal withdrawal reflex test, administration of the selective 5-HT1A agonists ipsapirone, gepirone and PAPP resulted in significant dose-dependent increases in receptive field (RF) area for withdrawal reflexes when compared to predrug baseline values, indicating an increase in nociceptive sensitivity. The average overall percent maximal increase in RF area following administration of 5-HT1A selective compounds was: 80 +/- 16% for the ventroflexion reflex, 90 +/- 6% for the dorsiflexion reflex and 87 +/- 8% for the lateral flexion reflex. Similar to the effects noted with 5-HT1A agonists, administration of 5-HT1B agonists RU24969, mCPP and TFMPP resulted in a hyperalgesic response with an overall percent maximal increase of 43 +/- 6% for the ventroflexion reflex, 51 +/- 6% for the dorsiflexion reflex and 38 +/- 9% for the lateral flexion reflex. In the tail-flick analgesiometric test, administration of the 5-HT1A agonists 8-OH-DPAT and ipsapirone and the 5-HT1B agonists RU24969 and mCPP resulted in a significant dose-dependent increase in tail-flick latencies when compared to predrug baseline values, indicating a decrease in nociceptive sensitivity to noxious thermal stimuli. No differences in magnitude of the effect of the two receptor subtypes were found, indicating that stimulation of either 5-HT1A or 5-HT1B receptors was equipotent in producing the antinociceptive tail-flick response.(ABSTRACT TRUNCATED AT 250 WORDS)
Murphy
A Z
AZ
Department of Physiology, University of Cincinnati College of Medicine, OH 45267-0559.
Murphy
R M
RM
Zemlan
F P
FP
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D006358:Hot Temperature; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology
D007211:Indoles; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D008711:Metergoline; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid