Effects of peripheral nerve injury on alpha-2A and alpha-2C adrenergic receptor immunoreactivity in the rat spinal cord

Neuropathic pain resulting from peripheral nerve injury can often be reliev ed by administration of alpha -adrenergic receptor antagonists. Tonic activ ation of alpha adrenergic receptors may therefore facilitate the hyperalges ia and allodynia associated with neuropathic pain. It is currently unclear whether alpha(2A) or alpha(2C)-adrenergic receptor subtypes are involved in the pro-nociceptive actions of alpha-adrenergic receptors under neuropathi c conditions. We therefore investigated the effects of peripheral nerve inj ury on the expression of these subtypes in rat spinal cord using immunohist ochemical techniques. In addition, neuropeptide Y immunoreactivity was exam ined as an internal control because it has previously been shown to be up-r egulated following nerve injury. We observed a decrease in alpha(2A)-adrene rgic receptor immunoreactivity in the spinal cord ipsilateral to three mode ls of neuropathic pain: complete sciatic nerve transection, chronic constri ction injury of the sciatic nerve and L5/L6 spinal nerve ligation. The exte nt of this down-regulation was significantly correlated with the magnitude of injury-induced changes in mechanical sensitivity. In contrast, alpha(2C) -adrenergic receptor immunoreactivity was only increased in the spinal nerv e ligation model; these increases did not correlate with changes in mechani cal sensitivity. Neuropeptide Y immunoreactivity was up-regulated in all mo dels examined. Increased expression of neuropeptide Y correlated with chang es in mechanical sensitivity. The decrease in alpha(2A)-adrenergic receptor immunoreactivity and the lack of consistent changes in alpha(2C)-adrenergic receptor immunoreactivity su ggest that neither of these receptor subtypes is likely to be responsible f or the abnormal adrenergic sensitivity observed following nerve injury. On the contrary, the decrease in alpha(2A)-adrenergic receptor immunoreactivit y following nerve injury may result in an attenuation of the influence of d escending inhibitory noradrenergic input into the spinal cord resulting in increased excitatory transmitter release following peripheral stimuli. (C) 1999 IBRO. Published by Elsevier Science Ltd.