Research into analgesic effect of ondansetron in persistent pain model in rats with central noradrenergic system lesion

Introduction. Many known substances affecting the serotoninergic system induce definite physiological effects, including those which are therapeutic. For instance, the enhanced serotoninergic transmission due to decreased functions of autoreceptors and increased inhibitory functions of postsynaptic 5-HT1A is associated with antidepressant effect. The central serotoninergic system takes part in the regulation of many bodily functions, such as sleep, wakefulness, blood pressure, pain perception or sexual behaviours. Moreover, it is involved in the pathogenesis of depression, anxiety, addictions, migraine and other headaches. In pain therapy, not only typical analgesics are used, but also substances without obvious analgesic effect, thus allowing potential pharmacological modulation of analgesic activity in the treatment of pain. Objective. The aim of the study was to determine whether a chemical lesion to the central noradrenergic system at an early stage of individual development alters reactivity of 5-HT3 receptors in adult rats. Materials and method. The study used newborn and adult Wistar rats aged 8–10 weeks. Behavioural tests (writhing test, formalin assay) were used to assess the analgesic action of ondansetron as a 5-HT3 receptor antagonist. Results. The analgesic effect of ondansetron (1.0 mg/kg b.w., i.p.) in the writhing test was weak and short. Pain intensity score after ondansetron injection (1.0 mg/kg b.w., i.p) was 2–3 points and did not differ significantly between the study groups. Conclusions. Damage to the central noradrenergic system at an early stage of individual development has no effect on the antinociceptive effects of the serotonin (5-HT3) receptor antagonist, ondansetron, in the persistent pain model.