Benedetti F, Amanzio M, Casadio C, Oliaro A, Maggi G
Dipartimento di Neuroscienze, Università di Torino, Corso Raffaello, Italy.
Pain. 1997 Jun;71(2):135-40. doi: 10.1016/s0304-3959(97)03346-0.
In patients who reported mild postoperative pain, we evoked a nocebo response, a phenomenon equal but opposite to placebo. Patients who gave informed consent to increase their pain for 30 min received a substance known to be non-hyperalgesic (saline solution) and were told that it produced a pain increase. A nocebo effect was observed when saline was administered. However, if a dose of 0.5 or 5 mg of the cholecystokinin antagonist proglumide was added to the saline solution, the nocebo effect was abolished. A dose of 0.05 mg of proglumide was ineffective. The blockade of the nocebo hyperalgesic response was not reversed by 10 mg of naloxone. These results suggest that cholecystokinin mediates pain increase in the nocebo response and that proglumide blocks nocebo through mechanisms not involving opioids. Since the nocebo procedure represents an anxiogenic stimulus and previous studies showed a role for cholecystokinin in anxiety, we suggest that nocebo hyperalgesia may be due to a cholecystokinin-dependent increase of anxiety.
在报告术后疼痛较轻的患者中，我们诱发了一种反安慰剂反应，这是一种与安慰剂作用相等但相反的现象。同意在30分钟内增加疼痛的患者接受了一种已知无致痛作用的物质（生理盐水），并被告知该物质会使疼痛加剧。注射生理盐水时观察到了反安慰剂效应。然而，如果在生理盐水中添加0.5或5毫克的胆囊收缩素拮抗剂丙谷胺，反安慰剂效应就会消失。0.05毫克的丙谷胺剂量无效。10毫克的纳洛酮不能逆转反安慰剂性痛觉过敏反应的阻断作用。这些结果表明，胆囊收缩素在反安慰剂反应中介导疼痛加剧，丙谷胺通过不涉及阿片类药物的机制阻断反安慰剂效应。由于反安慰剂程序是一种致焦虑刺激，且先前的研究表明胆囊收缩素在焦虑中起作用，我们认为反安慰剂性痛觉过敏可能是由于胆囊收缩素依赖的焦虑增加所致。
