Alpha-1A adrenoceptors modulate potentiation of spinal nociceptive pathways in the rat spinal cord in vitro.

The rat hemisected spinal cord preparation was used to assess the role of different adrenoceptor subtypes on the modulation of nociceptive reflexes. These were elicited by trains of high intensity electrical stimuli delivered to a lumbar dorsal root. Responses were recorded from the corresponding ventral root in AC- and DC-amplification modes simultaneously. Superfusion of noradrenaline produced a potentiation of action potential firing (AC channel) as well as a depression of the cumulative depolarisation (DC channel) in responses to repetitive afferent stimulation.Noradrenaline-induced potentiation of firing was mimicked by the alpha1A-adrenoceptor agonist A 61603 and the alpha1-adrenoceptor agonist methoxamine in a reversible and concentration-dependent manner. The order of potency of these agonists was A61603>>noradrenaline>methoxamine. The alpha(1A)-adrenoceptor antagonist 5-methyl-urapidil and the alpha1-adrenoceptor antagonist corynanthyne blocked the excitatory effects of noradrenaline. In contrast, the alpha(1B/D)-adrenoceptor antagonists chloroethylclonidine and BMY 7378 failed to block this effect.Noradrenaline-induced depression of cumulative depolarisation was mimicked by the alpha2-adrenoceptor agonist UK 14,304. In addition, this compound produced inhibition of firing in responses to afferent stimulation. These results show that noradrenaline has bi-directional modulatory effects on nociceptive reflexes and indicate that selective activation of alpha1A- but not alpha1B/D-adrenoceptors mediate potentiation of spinal nociceptive reflexes.