Norepinephrine-Induced Rekindling of Mechanical Allodynia in Sympathectomized Neuropathic Rat

Moon, Dong Eon

Abstract

BACKGROUND: Sympathectomy relieves pain in sympathectically maintained pain, and subcutaneous injection of norepinephrine (NE) can rekindle mechanical allodynia. However, the mechanism of rekindling is not clear. The purpose of this study is to investigate which subtype of alpha-adrenoceptor is involved in NE-induced rekindling of mechanical allodynia in sympathectomized neuropathic rats.
METHODS
Neuropathic injury was produced by tightly ligating the left L5 and L6 spinal nerves of 36 male Sprague-Dawley rats and bilateral lumbar sympathectomy was done at two weeks postoperatively. Starting at 7 days after sympathectomy, rekindling of mechanical allodynia was induced by NE and clonidine injected into the left paw, which was reversed by pretreatment of phentolamine and idazoxan. Mechanical allodynia was quantified by measuring the frequency of foot lifts to two von Frey filaments applied to the paw.
RESULTS
All tested rats displayed well-developed signs of mechanical allodynia at the left paw that were abolished by a bilateral lumbar sympathectomy. Subcutaneous (s.c.) injection of NE (0.05 microgram) into the affected paw of sympathectomized neuropathic rats rekindled previous mechanical allodynia. These effects could be mimicked by an alpha2,-receptor agonist clonidine, but not by an alpha1,-receptor agonist phenylephrine. The NE-induced rekindling of mechanical allodynia was significantly reduced by prior sc. injection of a mixed a-receptor antagonist phentolamine (20 microgram) and alpha,-receptor antagonist idazoxan (20 microgram), but not by a alpha1,-receptor antagonist terazosin (20 microgram). The pretreatment of idazoxan produced dose-related inhibition of NE-induced rekindling of mechanical allodynia. The rekindling induced by alpha2-receptor agonist clonidine (5 microgram) was also reversed by prior s.c. injection of alpha2-receptor antagonist idazoxan (20 microgram).
CONCLUSION
Subcutaneous injection of NE into the paw of sympathectomized neuropathic rats rekindles mechanical allodynia, which is reversed by an alpha2-, but not by an alpha1-receptor antagonist. Therefore, rekindling of mechanical allodynia in sympathectomized neuropathic rats is mediated by alpha2-adrenoceptor.