Role of spinal serotonin1 receptor subtypes in thermally and mechanically elicited nociceptive reflexes

The ability of 5-HT_1A and 5-HT_1B 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-HT_1A 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-HT_1A 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-HT_1A agonists, administration of 5-HT_1B 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-HT_1A agonists 8-OH-DPAT and ipsapirone and the 5-HT_1B 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-HT_1A or 5-HT_1B receptors was equipotent in producing the antinociceptive tail-flick response. Administration of the 5-HT_1A antagonist meter-goline completely reversed the increase in TFL produced by RU24969, providing further evidence that the effects seen here are mediated by spinal 5-HT receptors. The results of this study indicate that spinal 5-HT₁ receptor subtypes may either facilitate or inhibit nociceptive input depending upon the type of nociceptor that is activated, as opposed to the type of receptor subtype that is stimulated.