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 d ifferent adrenoceptor subtypes oil the modulation of nociceptive reflexes. These were elicited by trains of high intensity electrical Stimuli delivere d to a lumbar dorsal root. Responses were recorded from the corresponding v entral root in AC- and DC-amplification modes Simultaneously. Superfusion of noradrenaline produced a potentiation of action potential fi ring (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 alpha (1A) -adrenoceptor agonist A 61603 and the alpha (1)-adrenoceptor agonist methox amine in a reversible and concentration-dependent manner. The order of pote ncy of these agonists was A61603 > > noradrenaline > methoxamine. The alpha (1A)-adrenoceptor antagonist 5-methyl-urapidil and the alpha (1)-adrenocep tor antagonist corynanthyne blocked the excitatory effects of noradrenaline . In contrast, the alpha (1B/D)-adrenoceptor antagonists chloroethylclonidi ne and BMY 7378 failed to block this effect. Noradrenaline-induced depression of cumulative depolarisation was mimicked by the alpha (2)-adrenoeeptor 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 alpha (1 A)- but not alpha (1B/D)-adrenoceptors mediate potentiation or spinal nocic eptive reflexes. (C) 2001 Elsevier Science Ltd. All rights reserved.