Peripherally administered alpha2-adrenoceptor agonist in the modulation of chronic allodynia induced by spinal nerve ligation in the rat.

Abstract

We studied whether a peripherally administered alpha2-adrenoceptor agonist modulates mechanical allodynia caused by unilateral ligation of two spinal nerves in the rat. Medetomidine, an alpha2-adrenoceptor agonist, atipamezole, an alpha2-adrenoceptor antagonist, or saline (control) was administered into the footpad of either the allodynic or the contralateral hindpaw. Medetomidine (1-10 microg/kg in 50 microL) reversed the unilateral allodynia in a dose-dependent fashion independent of the site of administration. At this dose range, medetomidine did not influence the heat-induced tail-flick response. The antiallodynic effect of medetomidine was completely reversed by a dose of atipamezole that alone was ineffective (30 microg/kg). At the largest dose used (100 microg/kg in 50 microL), atipamezole decreased the latency of the heat-induced tail flick and had an ipsilateral allodynic effect in the injected paw when administered into the control side. The atipamezole-induced mechanical allodynia was not attenuated by medetomidine. The results indicate that an alpha2-adrenoceptor agonist at a subantinociceptive dose may significantly attenuate allodynia produced by spinal nerve ligation. This antiallodynic effect is not due to a peripheral action, but rather to action on central (presumably spinal) alpha2-adrenoceptors. The allodynic effect of a high concentration of atipamezole (100 microg/kg in 50 microL) in the injected paw can be explained by peripheral nonadrenergic mechanisms (e.g., local irritation). The present behavioral results indicate that a selective alpha2-adrenoceptor agonist at a subantinociceptive dose effectively attenuates mechanical allodynia induced by an experimental model of chronic neuropathy in the rat. This antiallodynic action can be explained by central, rather than peripheral, alpha2-adrenergic mechanisms.