α1-Adrenoceptors in Normal and Hyperalgesic Human Skin

1. Evidence of an adrenergic component of cutaneous hyperalgesia has recently been obtained in animal models of painful peripheral neuropathy. These findings have prompted speculation that an increased density or sensitivity of peripheral α-adrenoceptors contributes to sensory abnormalities and chronic neuropathic pain in conditions such as reflex sympathetic dystrophy. However, it is not known whether α-adrenoceptors are present at the site of nociception, either in hyperalgesic or normal skin. 2. We used the selective radioligand 125I-hydroxyphenyl-ethyl-aminomethyl-tetralone (HEAT) to label α1-adrenoceptors, and quantitative autoradiography to assess the relative density of these receptors in skin samples from seven normal individuals and from the hyperalgesic and pain-free limbs of five patients with reflex sympathetic dystrophy. The distribution of autoradiographic grains over the epidermis and dermis was investigated in 10 μm serial transverse sections. 3. α1-Adrenoceptors were identified in the epidermis and dermal papillae of normal individuals, and in the hyperalgesic and pain-free skin of patients with reflex sympathetic dystrophy. The density of α1-adrenoceptors was greater in the epidermis and dermal papillae than further down in the dermis. 4. The mean density of α1-adrenoceptors was significantly greater in the hyperalgesic skin of patients than in the skin of normal individuals (35.4 grains/1000 μm2 compared with 15.5 grains/1000 μm2, P > 0.01). The mean density of α1-adrenoceptors in the pain-free skin of patients (26.9 grains/1000 μm2) fell midway between receptor density in hyperalgesic skin and in the skin of normal individuals, and did not differ significantly from either. 5. Our findings indicate that α1-adrenoceptors are present in the epidermis, and suggest that their numbers may be increased in the hyperalgesic skin of patients with reflex sympathetic dystrophy. Further studies need to identify the dermal and epidermal cell types that express high densities of α1-adrenoceptors, and to investigate their normal function and role in neuropathic pain.