Up-Regulation of cutaneous α₁-adrenoceptors in complex regional pain syndrome type I

Background: In a small radioligand-binding study of cutaneous α₁-adrenoceptors in complex regional pain syndrome (CRPS), signal intensity was greater in the CRPS-affected limb than in controls. However, it was not possible to localize heightened expression of α₁-adrenoceptors to nerves, sweat glands, blood vessels, or keratinocytes using this technique. Methods: To explore this in the present study, skin biopsies were obtained from 31 patients with CRPS type I and 23 healthy controls of similar age and sex distribution. Expression of α₁-adrenoceptors on keratinocytes and on dermal blood vessels, sweat glands, and nerves was assessed using immunohistochemistry. Results: α₁-Adrenoceptors were expressed more strongly in dermal nerve bundles and the epidermis both on the affected and contralateral unaffected side in patients than in controls (P<0.05). However, expression of α₁-adrenoceptors in sweat glands and blood vessels was similar in patients and controls. α₁-Adrenoceptor staining intensity in the CRPS-affected epidermis was associated with pain intensity (P<0.05), but a similar trend for nerve bundles did not achieve statistical significance. Discussion: Epidermal cells influence nociception by releasing ligands that act on sensory nerve fibers. Moreover, an increased expression of α₁-adrenoceptors on nociceptive afferents has been shown to aggravate neuropathic pain. Thus, the heightened expression of α₁-adrenoceptors in dermal nerves and epidermal cells might augment pain and neuroinflammatory disturbances after tissue injury in patients with CRPS type I.