Up‐Regulation of Cutaneous α 1 ‐Adrenoceptors in Complex Regional Pain Syndrome Type I

Background In a small radioligand‐binding study of cutaneous α 1 ‐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 α 1 ‐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 α 1 ‐adrenoceptors on keratinocytes and on dermal blood vessels, sweat glands, and nerves was assessed using immunohistochemistry. Results α 1 ‐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 α 1 ‐adrenoceptors in sweat glands and blood vessels was similar in patients and controls. α 1 ‐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 α 1 ‐adrenoceptors on nociceptive afferents has been shown to aggravate neuropathic pain. Thus, the heightened expression of α 1 ‐adrenoceptors in dermal nerves and epidermal cells might augment pain and neuroinflammatory disturbances after tissue injury in patients with CRPS type I .