Interactions between noradrenergic and cholinergic mechanisms involved in spinal nociceptive processing

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Abstract
Antinociceptive effects have been demonstrated after systemic and spinal administration of the adrenoceptor agonist clonidine and cholinomimetic drugs in animals and human. The present investigation was undertaken in rats to study the possible interactions between spinal noradrenergic and cholinergic mechanisms in modulating the reaction to nociceptive stimuli. Using the tail immersion test, an additive antinociceptive effect was found between intrathecal (IT) clonidine (10 ug) and physostigmine (15 Ig, IT). The effect of clonidine was attenuated by atropine (15 μg, IT). Physostigmine (15 μg, IT) antinociception, which was of short duration was abolished by atropine (15 ug, IT) and attenuated by phentolamine (20 μg, IT). Neostigmine (5 μg, IT) produced a prolonged antinociceptive response. In animals pretreated with 6–hydroxydopamine IT, leading to a selective depletion of spinal cord noradrenaline, physostigmine (15 ug, IT) was ineffective in altering the nociceptive test response. Neither clonidine, nor physostigmine produced changes in latency times in the hot plate test (58C) in the doses employed. In conclusion, a clear–cut interaction exists between spinal noradrenergic and cholinergic systems for antinociception. To explain the interactions, several possible mechanisms may be considered, including cholinomimetic effects produced by clonidine, and the presence of muscarinic receptors in the dorsal horn of the spinal cord.