Martini M, Lee M C H, Valentini E, Iannetti G D
Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK; Department of Psychology, Sapienza University of Rome, Rome, Italy; Fondazione Santa Lucia, Scientific Institute for Research, Hospitalization and Health Care, Rome, Italy.
Eur J Neurosci. 2015 Feb;41(4):498-504. doi: 10.1111/ejn.12807. Epub 2014 Dec 19.
Suppression of spinal responses to noxious stimulation has been detected using spinal fMRI during placebo analgesia, which is therefore increasingly considered a phenomenon caused by descending inhibition of spinal activity. However, spinal fMRI is technically challenging and prone to false-positive results. Here we recorded laser-evoked potentials (LEPs) during placebo analgesia in humans. LEPs allow neural activity to be measured directly and with high enough temporal resolution to capture the sequence of cortical areas activated by nociceptive stimuli. If placebo analgesia is mediated by inhibition at spinal level, this would result in a general suppression of LEPs rather than in a selective reduction of their late components. LEPs and subjective pain ratings were obtained in two groups of healthy volunteers - one was conditioned for placebo analgesia while the other served as unconditioned control. Laser stimuli at three suprathreshold energies were delivered to the right hand dorsum. Placebo analgesia was associated with a significant reduction of the amplitude of the late P2 component. In contrast, the early N1 component, reflecting the arrival of the nociceptive input to the primary somatosensory cortex (SI), was only affected by stimulus energy. This selective suppression of late LEPs indicates that placebo analgesia is mediated by direct intracortical modulation rather than inhibition of the nociceptive input at spinal level. The observed cortical modulation occurs after the responses elicited by the nociceptive stimulus in the SI, suggesting that higher order sensory processes are modulated during placebo analgesia.
在安慰剂镇痛过程中，利用脊髓功能磁共振成像（fMRI）检测到对有害刺激的脊髓反应受到抑制，因此，安慰剂镇痛越来越被认为是一种由脊髓活动下行抑制引起的现象。然而，脊髓fMRI在技术上具有挑战性，并且容易出现假阳性结果。在此，我们记录了人类在安慰剂镇痛过程中的激光诱发电位（LEP）。LEP能够直接测量神经活动，并且具有足够高的时间分辨率，以捕捉由伤害性刺激激活的皮质区域序列。如果安慰剂镇痛是由脊髓水平的抑制介导的，这将导致LEP普遍受到抑制，而不是其晚期成分的选择性降低。在两组健康志愿者中获得了LEP和主观疼痛评分——一组接受安慰剂镇痛条件训练，另一组作为非条件对照组。将三种阈上能量的激光刺激施加到右手背部。安慰剂镇痛与晚期P2成分的幅度显著降低相关。相比之下，反映伤害性输入到达初级体感皮层（SI）的早期N1成分仅受刺激能量影响。晚期LEP的这种选择性抑制表明，安慰剂镇痛是由直接的皮质内调制介导的，而不是脊髓水平对伤害性输入的抑制。观察到的皮质调制发生在SI中伤害性刺激引发的反应之后，这表明在安慰剂镇痛过程中高阶感觉过程受到了调制。
