日前，北卡罗来纳大学教堂山分校 Grégory Scherrer团队在国际顶尖学术期刊 Nature 在线发表重要成果：“Neural circuit basis of placebo pain relief” ，该研究发现了安慰剂效应缓解疼痛的一个大脑神经回路——前扣带回皮质喙部（rACC）向脑桥核（Pn）的神经元投射（rACC→Pn）。2009届校友陈冲博士为该论文第一作者。

研究团队发现，由疼痛缓解预期产生的镇痛作用是由前扣带回皮质喙部（rACC）向脑桥核（Pn）的神经元投射（rACC→Pn）所介导的，而脑桥核（Pn）此前并未被发现在疼痛中有作用。对神经活动的体内钙成像和脑切片中的电生理记录表明，对疼痛缓解的预期会提高rACC→Pn神经元的活性，并增强该通路中的神经传递。抑制rACC→Pn通路会破坏安慰剂镇痛作用并降低疼痛阈值，而在没有安慰剂条件作用的情况下激活则会引发镇痛作用。

对疼痛缓解的预期激活了rACC→Pn通路

研究团队在小脑内发现了一个细胞簇——浦肯野细胞（Purkinje cell），这些细胞在疼痛缓解预期期间表现出类似于rACC→Pn神经元的活动模式，它们或许能编码rACC→Pn通路中的疼痛缓解预期，这为小脑在认知性疼痛调节中的作用提供了细胞水平的证据。这些发现为使用药物、电极神经刺激或认知行为疗法靶向前额皮质-脑桥-小脑通路来治疗和缓解疼痛开辟了可能性。

Abstract

Placebo effects are notable demonstrations of mind–body interactions. During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain—a phenomenon known as placebo analgesia. However, despite the strength of placebo effects and their impact on everyday human experience and the failure of clinical trials for new therapeutics, the neural circuit basis of placebo effects has remained unclear. Here we show that analgesia from the expectation of pain relief is mediated by rostral anterior cingulate cortex (rACC) neurons that project to the pontine nucleus (rACC→Pn)—a precerebellar nucleus with no established function in pain. We created a behavioural assay that generates placebo-like anticipatory pain relief in mice. In vivo calcium imaging of neural activity and electrophysiological recordings in brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an abundance of opioid receptors, further suggesting a role in pain modulation. Inhibition of the rACC→Pn pathway disrupted placebo analgesia and decreased pain thresholds, whereas activation elicited analgesia in the absence of placebo conditioning. Finally, Purkinje cells exhibited activity patterns resembling those of rACC→Pn neurons during pain-relief expectation, providing cellular-level evidence for a role of the cerebellum in cognitive pain modulation. These findings open the possibility of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain.

2009届麻醉学专业校友，美国北卡莱罗纳大学教堂山分校神经科学家，研究领域为Neurobiology of Pain and Opioids，专注于疼痛、阿片类药物和麻醉的研究。近年来先后获得Stanford School of Medicine Dean’s Postdoctoral Fellowship，Inscopix Tech Award，Society of General Physiologists Annual Meeting Poster Award，IARS Mentored Research Awards (IMRA)等奖项。