Modulation of afferent-evoked neurotransmission by 5-HT3 receptors in young rat dorsal horn neurones in vitro: a putative mechanism of 5-HT3 induced anti-nociception

1 The in vitro hemisected spinal cord from young rat was used to investigat e the mechanism of serotoninergic modulation of primary afferent-mediated s ynaptic transmission in the dorsal horn through activation of the 5-HT3 rec eptor. 2 Dorsal root-evoked excitatory post-synaptic potentials (DR-EPSPs) were re corded intracellularly from dorsal horn neurones. Extracellular recordings of the population primary afferent depolarization (PAD) and the dorsal root -evoked dorsal root reflex (DR-DRR) were made from segmental dorsal roots. 3 5-Hydroxytryptamine (5-HT) and the selective 5-HT3 receptor agonist 1-(m- chloro-phenyl)biguanide hydrochloride (m-ChPB) (10 and 50 mu M) induced sta tistically significant reductions of the DR-EPSP amplitude (P<0.001) and du ration (P<0.001) in the majority of dorsal horn neurones. The 5-HT3 recepto r selective antagonists 3-Tropanyl-indole-3-carboxylate hydrochloride (Trop isetron, 10 mu M) and N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-o xo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide (Y-25130, 10 mu M) abolishe d m-ChPB-induced DR-EPSP attenuation and partially blocked the 5-HT effect. 4 m-ChPB (50 mu M)-induced DR-EPSP amplitude and duration attenuation was r etained in the presence of the GABA(A) receptor antagonist bicuculline (30 mu M), the GABA(B) receptor antagonist saclofen (50 mu M) and the opioid re ceptor antagonist naloxone (50 mu M). 5 Both 5-HT and m-ChPB (10 and 50 mu M) induced a PAD but the mean peak amp litude of 5-HT-induced PAD was significantly greater than PAD to m-ChPB (98 .6+/-12 mu V compared to 51.8+/-10 mu V for 50 mu M of agonist, respectivel y). Tropisetron partially reduced 5-HT-induced PAD and abolished m-ChPB-ind uced PAD. 5-HT, but not m-ChPB, significantly (P<0.001) reduced the peak am plitude of the DR-DRR and this action of 5-HT was unaffected by Tropisetron or Y-25130. 6 These data provide experimental evidence for a putative cellular mechanis m at the level of the dorsal horn for anti-nociceptive effects of 5-HT3 rec eptor activation. This 5-HT3-mediated modulation of sensory afferent transm ission was evidently independent of inhibitory GABA- or opioid-dependent in terneuronal pathways. The extent to which the 5-HT3 receptor could be invol ved in the operation of endogenous analgesia and sensory modulation by desc ending monoamine bulbospinal pathways is discussed.