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Pain sensitivity and analgesis response in Wistar- Zagreb 5HT rats with constitutionally altered serotonin transporter

It is known that serotonin (5-hydroxytryptamine, 5HT) system modulates nociceptive response acting through both, central and peripheral nervous system, but its contribution to pain sensitivity and analgesic response remained to be fully understood. Here, we studied serotonergic modulation of pain behaviour using a genetic animal model of rats with constitutional differences in 5HT homeostasis (Wistar-Zagreb 5HT rats), developed by selective breeding for the extreme activities of peripheral 5HT transporter (5HTT). Besides in periphery, two sublines (high- 5HT and low-5HT) of this model differ also in the central 5HT homeostasis, as evidenced from neurochemical and behavioural studies. By measuring paw withdrawal latency (PWL) to the radiant heat stimulation (Hargreaves test) we assessed 1) baseline thermal pain sensitivity and 2) analgesic effect of various drugs (tramadol, clomipramine, fluvoxamine) in animals from high- 5HT and low-5HT sublines. We demonstrated that, in acute model of nociception, animals from the high- 5HT subline are less sensitive to thermal stimuli at baseline (have higher PWL values) and that animals from the low-5HT subline show better response to selected analgesic drugs (tramadol, clomipramine), when compared to the counterpart low-5HT subline. Observed differences in pain sensitivity and analgesic response between high- 5HT and low-5HT sublines support a contribution of 5HT system and, specifically, functional 5HTT in the control of pain behaviour. Results also validate our Wistar- Zagreb 5HT rats as a potential model to study the role of endogenous 5HT tone in the physiology and pharmacology of pain perception/behaviour.

pain; serotonin; Wistar-Zagreb 5HT rats

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