Lamusuo S, Hirvonen J, Lindholm P, Martikainen I K, Hagelberg N, Parkkola R, Taiminen T, Hietala J, Helin S, Virtanen A, Pertovaara A, Jääskeläinen S K
Department of Neurology, Turku University Hospital, Finland.
Division of Clinical Neuroscience, University of Turku, Finland.
Eur J Pain. 2017 Oct;21(9):1505-1515. doi: 10.1002/ejp.1052. Epub 2017 May 11.
Repetitive transcranial magnetic stimulation (rTMS) at M1/S1 cortex has been shown to alleviate neuropathic pain.
To investigate the possible neurobiological correlates of cortical neurostimulation for the pain relief.
We studied the effects of M1/S1 rTMS on nociception, brain dopamine D2 and μ-opioid receptors using a randomized, sham-controlled, double-blinded crossover study design and 3D-positron emission tomography (PET). Ten healthy subjects underwent active and sham rTMS treatments to the right M1/S1 cortex with E-field navigated device. Dopamine D2 and μ-receptor availabilities were assessed with PET radiotracers [ C]raclopride and [ C]carfentanil after each rTMS treatment. Thermal quantitative sensory testing (QST), contact heat evoked potential (CHEP) and blink reflex (BR) recordings were performed between the PET scans.
μ-Opioid receptor availability was lower after active than sham rTMS (P ≤ 0.0001) suggested release of endogenous opioids in the right ventral striatum, medial orbitofrontal, prefrontal and anterior cingulate cortices, and left insula, superior temporal gyrus, dorsolateral prefrontal cortex and precentral gyrus. There were no differences in striatal dopamine D2 receptor availability between active and sham rTMS, consistent with lack of long-lasting measurable dopamine release. Active rTMS potentiated the dopamine-regulated habituation of the BR compared to sham (P = 0.02). Thermal QST and CHEP remained unchanged after active rTMS.
rTMS given to M1/S1 activates the endogenous opioid system in a wide brain network associated with processing of pain and other salient stimuli. Direct enhancement of top-down opioid-mediated inhibition may partly explain the clinical analgesic effects of rTMS.
Neurobiological correlates of rTMS for the pain relief are unclear. rTMS on M1/S1 with C-carfentanyl-PET activates endogenous opioids. Thermal and heat pain thresholds remain unchanged. rTMS induces top-down opioid-mediated inhibition but not change the sensory discrimination of painful stimuli.
已证实对M1/S1皮质进行重复经颅磁刺激（rTMS）可缓解神经性疼痛。
研究皮质神经刺激缓解疼痛可能的神经生物学相关性。
我们采用随机、假刺激对照、双盲交叉研究设计及三维正电子发射断层扫描（PET），研究M1/S1区rTMS对痛觉、脑多巴胺D2和μ-阿片受体的影响。10名健康受试者使用电场导航设备接受对右侧M1/S1皮质的真刺激和假刺激rTMS治疗。每次rTMS治疗后，用PET放射性示踪剂[ C]雷氯必利和[ C]卡芬太尼评估多巴胺D2和μ受体的可用性。在PET扫描之间进行热定量感觉测试（QST）、接触热诱发电位（CHEP）和眨眼反射（BR）记录。
真刺激rTMS后μ-阿片受体可用性低于假刺激（P≤0.0001），提示右侧腹侧纹状体、内侧眶额皮质、前额叶皮质和前扣带回皮质以及左侧岛叶、颞上回、背外侧前额叶皮质和中央前回释放内源性阿片类物质。真刺激和假刺激rTMS之间纹状体多巴胺D2受体可用性无差异，这与缺乏持久可测量的多巴胺释放一致。与假刺激相比，真刺激rTMS增强了BR的多巴胺调节习惯化（P = 0.02）。真刺激rTMS后热QST和CHEP保持不变。
对M1/S1给予rTMS可激活与疼痛及其他显著刺激处理相关的广泛脑网络中的内源性阿片系统。自上而下阿片介导抑制的直接增强可能部分解释了rTMS的临床镇痛效果。
rTMS缓解疼痛的神经生物学相关性尚不清楚。用[ C]卡芬太尼-PET对M1/S1进行rTMS可激活内源性阿片类物质。热痛和热阈值保持不变。rTMS诱导自上而下的阿片介导抑制，但不改变对疼痛刺激的感觉辨别。
