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

Abstract

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)

The potentiation of analgesic activity of paracetamol plus morphine involves the serotonergic system in rat brain

“…Pretreatment with naloxone prevented the increase of 5-HT in both areas (Fig. 5); [F (1,20) ¼10.7; p < 0.01], [F (1,20) ¼12.2; p < 0.01] for pons and cortex respectively.…”

“…The levels of serotonin in the cortex and in the pons were significantly increased by the antinociceptive combination of PARA 100 mg/kg and morphine 3 mg/kg, while they did not change the values of controls when given alone (Fig. 4); the interaction test showed a potentiation in the two areas [F (1,20) ¼15.2; p < 0.01], [F (1,20) ¼28.2; p < 0.01] for pons and cortex respectively. Pretreatment with naloxone prevented the increase of 5-HT in both areas (Fig.…”

“…The serotonergic system can play a role in the antinociceptive mechanism of some NSAIDs; it has been also proposed that other neurotransmitter systems, including opiatergic pathways, may be involved in the central analgesic effect of this class of drugs [13,[20][21][22].…”

Effect of intrathecal serotonin on nociception in rats: influence of the pain test used

“…Authors have shown that the nociceptive test and the quality of the noxious stimulus used for assessing animal sensitivity are of critical importance Murphy et al 1992). A great majority of behavioural tests used in studies with 5-HT or 5-HT receptor agonists are thermal tests and mainly the tail-flick test.…”

Exogenous gaseous superoxide potentiates the antinociceptive effect of opioid analgesic agents

“…Under different experimental conditions serotonin may facilitate, produce no effect on, or reduce, behaviourally defined analgesia [9]. The serotoninergic pathway in the CNS can mediate antinociception and is involved in the expression of the antinociceptive action of opioids [10].…”