Hord A H, Denson D D, Stowe B, Haygood R M
Department of Anesthesiology, Division of Pain Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Anesth Analg. 2001 Jun;92(6):1558-62. doi: 10.1097/00000539-200106000-00042.
Phentolamine, a nonspecific alpha 1- and alpha 2-adrenergic antagonist, relieves pain in patients with reflex sympathetic dystrophy. We sought to determine whether phentolamine, prazosin (alpha 1 antagonist), or SKF86466 (alpha 2 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 min and repeated at 15-min intervals for 1 h. Phentolamine, prazosin, and SKF86466 1, 2, and 5 mg/kg provided statistically significant analgesia in rats with CCI for at least 65 min. PWL did not return to baseline levels after 1 or 2 mg/kg of prazosin or SKF86466 but did so after 35 min after phentolamine 2 mg/kg. After 5 mg/kg, PWL returned to preoperative values between 5 and 50 min for phentolamine, at 35 and 65 min for prazosin, and at 50 min for SKF86466. We conclude that both alpha1 and alpha2 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 alpha1 and alpha2 antagonists in a dose-dependent manner.
酚妥拉明是一种非特异性的α1和α2肾上腺素能拮抗剂，可缓解反射性交感神经营养不良患者的疼痛。我们试图确定酚妥拉明、哌唑嗪（α1拮抗剂）或SKF86466（α2拮抗剂）是否能缓解神经性疼痛大鼠的热痛觉过敏。在制造慢性压迫性损伤（CCI）4天后，通过测量爪部退缩潜伏期（PWL）来测试热痛觉过敏。分别注射剂量为1、2或5mg/kg的酚妥拉明、哌唑嗪或SKF86466后，在5分钟时测量PWL，并以15分钟的间隔重复测量1小时。酚妥拉明、哌唑嗪和SKF86466的1、2和5mg/kg剂量在CCI大鼠中提供了至少65分钟的统计学显著镇痛作用。1或2mg/kg的哌唑嗪或SKF86466后PWL未恢复到基线水平，但2mg/kg酚妥拉明注射35分钟后恢复到基线水平。5mg/kg后，酚妥拉明在5至50分钟之间、哌唑嗪在35和65分钟之间以及SKF86466在50分钟时PWL恢复到术前值。我们得出结论，交感神经系统的α1和α2外周受体均参与了由CCI引起的热痛觉过敏，并且热痛觉过敏可被α1和α2拮抗剂以剂量依赖的方式逆转。
