From the Sagol Brain Institute (L.W., T.H., H.S.), Institute of Pain Medicine, Department of Anesthesiology and Critical Care Medicine (L.D., S.B., H.S.), and Department of Internal Medicine F (G.J.), Tel-Aviv Sourasky Medical Center; Sagol School of Neuroscience (L.W., T.H.) and Sackler School of Medicine (L.D., T.H., G.J., H.S.), Tel Aviv University, Israel; Department of Anesthesia (H.N.-A.), Cincinnati Children's Hospital Medical Center, OH; and Pain Management & Neuromodulation Centre (H.S.), Guy's & St Thomas' NHS Foundation Trust, London, UK.
Neurology. 2018 Oct 2;91(14):e1285-e1294. doi: 10.1212/WNL.0000000000006293. Epub 2018 Sep 5.
To characterize the functional brain changes involved in δ-9-tetrahydrocannabinol (THC) modulation of chronic neuropathic pain.
Fifteen patients with chronic radicular neuropathic pain participated in a randomized, double-blind, placebo-controlled trial employing a counterbalanced, within-subjects design. Pain assessments and functional resting state brain scans were performed at baseline and after sublingual THC administration. We examined functional connectivity of the anterior cingulate cortex (ACC) and pain-related network dynamics using graph theory measures.
THC significantly reduced patients' pain compared to placebo. THC-induced analgesia was correlated with a reduction in functional connectivity between the anterior cingulate cortex (ACC) and the sensorimotor cortex. Moreover, the degree of reduction was predictive of the response to THC. Graph theory analyses of local measures demonstrated reduction in network connectivity in areas involved in pain processing, and specifically in the dorsolateral prefrontal cortex (DLPFC), which were correlated with individual pain reduction.
These results suggest that the ACC and DLPFC, 2 major cognitive-emotional modulation areas, and their connections to somatosensory areas, are functionally involved in the analgesic effect of THC in chronic pain. This effect may therefore be mediated through induction of functional disconnection between regulatory high-order affective regions and the sensorimotor cortex. Moreover, baseline functional connectivity between these brain areas may serve as a predictor for the extent of pain relief induced by THC.
描述 δ-9-四氢大麻酚（THC）调节慢性神经性疼痛所涉及的大脑功能变化。
15 名患有慢性神经根性神经病理性疼痛的患者参与了一项随机、双盲、安慰剂对照试验，采用平衡、内个体设计。在基线和舌下给予 THC 后进行疼痛评估和功能静息态脑扫描。我们使用图论测量法检查了前扣带皮层（ACC）和与疼痛相关的网络动力学的功能连接。
与安慰剂相比，THC 显著降低了患者的疼痛。THC 诱导的镇痛作用与前扣带皮层（ACC）和感觉运动皮层之间的功能连接减少有关。此外，减少的程度与对 THC 的反应有关。局部测量的图论分析表明，与疼痛处理相关的区域（特别是背外侧前额叶皮层，DLPFC）的网络连接减少，与个体疼痛减轻相关。
这些结果表明，ACC 和 DLPFC（两个主要的认知-情绪调节区域）及其与躯体感觉区域的连接，在 THC 治疗慢性疼痛的镇痛作用中具有功能性。因此，这种作用可能是通过诱导调节性高级情感区域和感觉运动皮层之间的功能去连接来介导的。此外，这些大脑区域之间的基线功能连接可能作为 THC 诱导的疼痛缓解程度的预测因子。
