Antinociceptive effect of paracetamol in rats is partly dependent on spinal serotonergic systems

https://doi.org/10.1016/0014-2999(91)90036-PGet rights and content

Abstract

The possible involvement of bulbo-spinal monoaminergic pathways in the antinociceptive effect of paracetamol was investigated in rats. Serotonergic pathways were lesioned with intrathecal 5,6-dihydroxytryptamine (5,6-DHT), and noradrenergic pathways with 6-hydroxydopamine (6-OHDA). Intact and lesioned rats were tested in the formalin test after i.p. paracetamol (400 mg/kg) or vehicle. Behaviour was scored for 1 h after the dorsal injection of 100 μ1 of 5% formalin into one hind paw. Behavioural variables were evaluated with a multivariate statistical procedure, as well as an analysis of variance. Paracetamol itself reduced pain-related behaviour and increased normal motor activity. This antinociceptive effect was reduced in rats lesioned with 5,6-DHT. In lesioned rats paracetamol caused a change in nociceptive behaviour from active, focused behaviour towards passive, protective and non-focused behaviour in the early phase of the formalin test. No significant effect of lesioning with 6-OHDA upon the paracetamol effect was found. These results show that activation of spinal serotonergic systems is involved in the antinociceptive effect of paracetamol. The relative importance of this mechanism in the central effect of paracetamol and the mechanisms that cause the activation remain to be determined.

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    Intraperitoneal injection of acetaminophen has been reported to induce a significant increase in 5-hydroxytryptamine (5-HT) concentration in the pontine and cortical areas [17]. The analgesic effect of acetaminophen is reported to be mediated, at least in part, by the activation of the spinal 5-HT receptor [14-16,2,23,3,5,7]. These data suggest that the analgesic effect of acetaminophen may involve the spinal 5-HT system.

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