Increased expression of cutaneous a1-adrenoceptors after chronic constriction injury in rats

a1-Adrenoceptor expression on nociceptors may play an important role in sympathetic-sensory coupling in certain neuropathic pain syndromes. The aim of this study was to determine whether a1-adrenoceptor expression was upregulated on surviving peptidergic, nonpeptidergic, and myelinated nerve fiber populations in the skin after chronic constriction injury of the sciatic nerve in rats. Seven days after surgery, a1-adrenoceptor expression was upregulated in the epidermis and on dermal nerve fibers in plantar skin ipsilateral to the injury but not around blood vessels. This a1-adrenoceptor upregulation in the plantar skin was observed on all nerve fiber populations exam- ined. However, a1-adrenoceptor expression was unaltered in the dorsal hind paw skin after the injury. The increased expression of a1-adrenoceptors on cutaneous nociceptors in plantar skin after chronic constriction injury suggests that this may be a site of sensory-sympathetic coupling that in- creases sensitivity to adrenergic agonists after nerve injury. In addition, activation of upregulated a1-adrenoceptors in the epidermis might cause release of factors that stimulate nociceptive signaling.Our findings indicate that peripheral nerve injury provokes upregulation of a1-adre-noceptors on surviving nociceptive afferents and epidermal cells in the skin. This might contribute to sympathetically maintained pain in conditions such as complex regional pain syndrome, painful diabetic neuropathy, and postherpetic neuralgia.