alpha-1 and alpha-2 adrenergic antagonists relieve thermal hyperalgesia in experimental mononeuropathy from chronic constriction injury. (Emory University School of Medicine, Atlanta, GA) Anesth Analg. 2001;92:1558-1562.

Phentolamine, a nonspecific α1- and α2-adrenergic antagonist, relieves pain in patients with reflex sympathetic dystrophy. This study sought to determine whether phentolamine, prazosin (α1 antagonist), or SKF86466 (α2 antagonist) relieve thermal hyperalgesia in rats with neuropathic pain. Four days after producing a chronic constriction injury (CCI), thermal hyperalgesia was tested by measuring paw withdrawal latency (PWL). After injection of phentolamine, prazosin, or SKF86466 each at doses of 1, 2, or 5 mg/kg, PWL tests were measured at 5 minutes and repeated at 15-minute intervals for 1 hour. Phentolamine, prazosin, and SKF86466 1, 2, and 5 mg/kg provided statistically significant analgesia in rats with CCI for at least 65 minutes. PWL did not return to baseline levels after 1 or 2 mg/kg of prazosin or SKF86466 but did so after 35 minutes after phentolamine 2 mg/kg. After 5 mg/kg, for phentolamine, at 35 and 65 minutes for prazosin, and at 50 minutes for SKF86466, and at 50 minutes for SKF86466. Conclude that both α1 and α2 peripheral receptors of the sympathetic nervous system are involved in the thermal hyperalgesia caused by CCI and that thermal hyperalgesia can be reversed by both α1 and α2 antagonists in a dose-dependent manner.