Eisenach J C, Hood D D, Curry R, Tong C
Department of Anesthesia, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina, USA.
Anesthesiology. 1997 Jun;86(6):1279-87. doi: 10.1097/00000542-199706000-00008.
Intradermal injection of capsaicin produces brief pain followed by hyperalgesia and allodynia in humans, and the latter effects are mediated by spinal N-methyl-D-aspartate mechanisms. Amitriptyline recently was shown to antagonize N-methyl-D-aspartate receptors, and in this study, the authors sought to determine the effect of amitriptyline alone and with the opioid alfentanil on hyperalgesia and allodynia produced by intradermal injection of capsaicin.
Forty-six healthy volunteers in the general clinical research center received repeated intradermal injections of capsaicin (100 microg) alone or before and after systemic injection of 4 mg midazolam, 25 mg amitriptyline, alfentanil by computer-controlled infusion, or amitriptyline plus alfentanil. Acute pain and areas of mechanical hyperalgesia and allodynia were determined at specified intervals. Blood was obtained for alfentanil and amitriptyline assay.
Capsaicin injection produced acute pain followed by hyperalgesia and allodynia. Alfentanil reduced these pain responses in a plasma-concentration-dependent manner, and reduction in hyperalgesia and allodynia correlated with reduction in acute pain. Amitriptyline alone had no effect and did not potentiate alfentanil. Alfentanil produced concentration-dependent nausea, an effect diminished by amitriptyline.
These data correspond with previous studies in volunteers demonstrating reduction in hyperalgesia and allodynia after intradermal injection of capsaicin by systemically administered opioids, and they suggest that this reduction may be secondary to reduced nociceptive input by acute analgesia. These data do not support the use of acute systemic administration of amitriptyline for acute pain, hyperalgesia, and allodynia, although the roles of chronic treatment and spinal administration are being investigated.
皮内注射辣椒素可使人体产生短暂疼痛，随后出现痛觉过敏和异常性疼痛，且后者是由脊髓N-甲基-D-天冬氨酸机制介导的。最近有研究表明阿米替林可拮抗N-甲基-D-天冬氨酸受体，在本研究中，作者试图确定单独使用阿米替林以及与阿片类药物阿芬太尼联合使用时，对皮内注射辣椒素所产生的痛觉过敏和异常性疼痛的影响。
46名健康志愿者在综合临床研究中心接受了单独皮内重复注射辣椒素（100微克），或在全身注射4毫克咪达唑仑、25毫克阿米替林、通过计算机控制输注阿芬太尼，或阿米替林加阿芬太尼之前和之后进行皮内重复注射辣椒素。在特定时间间隔测定急性疼痛以及机械性痛觉过敏和异常性疼痛的区域。采集血液用于阿芬太尼和阿米替林的检测。
注射辣椒素产生急性疼痛，随后出现痛觉过敏和异常性疼痛。阿芬太尼以血浆浓度依赖的方式减轻这些疼痛反应，痛觉过敏和异常性疼痛的减轻与急性疼痛的减轻相关。单独使用阿米替林没有效果，也不能增强阿芬太尼的作用。阿芬太尼产生浓度依赖性恶心，阿米替林可减轻这种作用。
这些数据与之前在志愿者中的研究一致，表明全身给予阿片类药物后，皮内注射辣椒素所产生的痛觉过敏和异常性疼痛减轻，提示这种减轻可能是急性镇痛减少伤害性传入的继发结果。这些数据不支持急性全身给予阿米替林用于治疗急性疼痛、痛觉过敏和异常性疼痛，尽管正在研究其慢性治疗和脊髓给药的作用。
