Noradrenaline induces peripheral antinociception by endogenous opioid release

Abstract

Background: The aim of this study was to investigate this involvement in not inflammatory model of pain and which opioid receptor subtype mediates noradrenaline-induced peripheral antinociception. Noradrenaline is involved in the intrinsic control of pain-inducing pro-nociceptive effects in the primary afferent nociceptors. However, inflammation can induce various plastic changes in the central and peripheral noradrenergic system that, upon interaction with the immune system, may contribute, in part, to peripheral antinociception.

Methods: Hyperalgesia was induced by intraplantar injection of prostaglandin E₂ (PGE₂, 2μg) into the plantar surface of the right hind paw and the paw pressure test to evaluated the hyperalgesia was used. Noradrenaline (NA) was administered locally into right hind paw of Wistar rat (160-200g) alone and after either agents, α₂-adrenoceptor antagonist yohimbine, α₁-adrenoceptor antagonist prazosin, β-adrenoceptor antagonist propranolol, μ-opioid antagonist clocinnamox, δ-opioid antagonist naltrindole and κ-opioid antagonist nor-binaltorfimina. In addition, the enkephalinase inhibitor bestatin was administered prior to NA low dose.

Results: Intraplantar injection of NA induced peripheral antinociception against hyperalgesia induced by PGE₂. This effect was reversed, in dose dependent manner, by intraplantar injection of yohimbine, prazosin, propranolol, clocinnamox and naltrindole. However, injection of nor-binaltorfimina did not alter antinociception of NA after PGE₂ hyperalgesia. Bestatin intensified the antinociceptive effects of low-dose of NA.

Conclusion: Besides the α₂-adrenoceptor, the present data provide evidence that, in absence of inflammation, NA activating α₁ and β-adrenoceptor induce endogenous opioid release to produce peripheral antinociceptive effect by μ and δ opioid receptors.

Keywords: Adrenoceptors; Noradrenaline; Noradrenergic system; Peripheral antinociception.