Effects of Alpha-adrenergic Agonists on Pain Modulation in Diffuse Noxious Inhibitory Control

Background: Diffuse noxious inhibitory control (DNIC) is thought to be mediated by neural networks in supraspinal brain structures. The descending antinociceptive system (DAS) is an important component of the DNIC neural network, but the precise structure of the neural network and the related neurotransmitters have not been examined.

Methods: The study was designed to examine whether systemic administration of the adrenergic agonists dexmedetomidine (DEX) and phenylephrine (PE) influences DNIC in the rat. Changes in the C-fiber reflex evoked by electromyographic activity were recorded following noxious tail immersion in hot water.

Results: Inhibition of the C-fiber reflex by the conditioning stimuli was reduced from 77.1 +/- 22.6% to 26.6 +/- 38.2% with continuous administration of DEX, and restored to 58.3 +/- 29.2% by intramuscular injection of atipamezole hydrochloride(APZ), a selective alpha 2-adrenoceptor antagonist. Inhibition of the C-fiber reflex was reduced from 75.6 +/- 25.8% to 22.7 +/- 38.9% with continuous administration of PE, and restored to 84.9 +/- 9.7% by intramuscular injection of phentolamine mesylate (PT), an alpha-adrenoceptor antagonist.

Conclusion: The results show that clinical doses of DEX and PE inhibit DNIC, thereby affecting and modulating the intrinsic pain inhibition system. These findings suggest that adrenergic neurons are involved in DNIC.