Expression of Cutaneous Beta-2 Adrenoceptors Is Similar in Patients with Complex Regional Pain Syndrome and Pain-Free Controls

OBJECTIVE: Studies in rodents suggest that cutaneous beta-2 adrenoceptors (β2-ARs) mediate inflammation and pain after tissue injury and that inflammation and peripheral nerve injury trigger increases in neuronal β2-AR expression. Hence, the aim of this study was to investigate the expression of β2-ARs on keratinocytes and dermal nerves in patients with complex regional pain syndrome (CRPS). DESIGN, SETTING, AND SUBJECTS: Fifty-eight patients with CRPS were recruited for this study. In addition, skin biopsies were obtained from 13 pain-free women and three pain-free men of similar age and sex distribution as the patients. METHODS: Quantitative sensory tests for assessing sensitivity to pressure, pinprick, light touch, heat, and cold were administered, and skin biopsies were obtained from the affected and contralateral limbs. Skin biopsies were also obtained from a similar site on the dorsal hand or foot of pain-free controls. Immunohistochemistry and confocal microscopy were used to identify β2-ARs on keratinocytes, dermal nerves, and blood vessels in the skin samples. RESULTS: The distribution of β2-ARs in keratinocytes and nerves was similar in the affected and contralateral limbs of patients and was similar for target cells in patients and controls. However, elevated β2-AR expression in reticular nerve bundles was associated with heightened sensitivity to heat pain. CONCLUSIONS: These findings do not support a major role of cutaneous β2-ARs in CRPS. However, activation of neuronal β2-ARs may contribute to thermal hyperalgesia in a subgroup of patients. Whether activation of β2-ARs on keratinocytes mediates inflammation early in the course of CRPS requires further investigation.