Placebo analgesia has great potential to overcome the inadequacies of current drug therapies to treat conditions of chronic pain. The rostral ventromedial medulla (RVM) has been implicated as a critical relay in the antinociceptive pathway underpinning placebo analgesia in humans. We developed a model of opiate-conditioned placebo analgesia in rats with neuropathic injury to identify medullary nuclei active during placebo analgesia. Using female and male rats the degree of thermal allodynia was first determined following nerve injury, and a pharmacological conditioning procedure, pairing contextual cues with the experience of morphine-induced analgesia, was used to elicit placebo analgesic reactions. This protocol revealed clear subpopulations of placebo reactors (36% of males, 25% of females) and non-reactors in proportions similar to those reported in human studies. We detected injury-specific c-Fos expression in the gracile nucleus and morphine-specific c-Fos expression in the serotonergic midline raphe nuclei and the caudal nuclei of the solitary tract. However, c-Fos expression did not differ between placebo reactors and non-reactors in either serotonergic or non-serotonergic neurons of the RVM. Despite a subpopulation of rats demonstrating placebo reactions, we found no evidence for enhanced activity in the nuclei from which the classical RVM → spinal cord descending analgesic pathways emerge.

安慰剂镇痛具有巨大的潜力，可以克服目前治疗慢性疼痛的药物疗法的不足。延髓腹侧延髓（RVM）已被认为是支撑安慰剂镇痛作用的抗伤害感受途径中的关键继电器。我们在患有神经性损伤的大鼠中开发了以鸦片为条件的安慰剂镇痛模型，以确定在安慰剂镇痛过程中活跃的髓核。首先使用雌性和雄性大鼠确定神经损伤后的热异常性疼痛程度，然后使用药理条件处理程序（将上下文线索与吗啡诱导的镇痛经验相结合）引发安慰剂镇痛反应。该方案揭示了安慰剂反应器的明确亚群（36％的男性，25％的女性）和非反应者的比例与人类研究中报告的比例相似。我们在睫状核中检测到了损伤特异性的c-Fos表达，在血清素能中线网状核和尾部尾核中检测到了吗啡特异性的c-Fos表达。但是，RVM的血清素能或非血清素能神经元的安慰剂反应器和非反应器之间的c-Fos表达没有差异。尽管有一群显示安慰剂反应的大鼠亚群，但我们没有发现增加经典RVM→脊髓下行镇痛途径的细胞核活性的证据。在RVM的血清素能或非血清素能神经元中，安慰剂反应器和非反应器之间的c-Fos表达没有差异。尽管有一群显示安慰剂反应的大鼠亚群，但我们没有发现增加经典RVM→脊髓下行镇痛途径的细胞核活性的证据。在RVM的血清素能或非血清素能神经元中，安慰剂反应器和非反应器之间的c-Fos表达没有差异。尽管有一群显示安慰剂反应的大鼠亚群，但我们没有发现增加经典RVM→脊髓下行镇痛途径的细胞核活性的证据。