CT-guided injection of a TRPV1 agonist around dorsal root ganglia decreases pain transmission in swine.
CT-guided injection of a TRPV1 agonist around dorsal root ganglia decreases pain transmission in swine.
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DOI：
10.1126/scitranslmed.aac6589
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发表时间：
2015-09-16
影响因子：
17.1
通讯作者：
Dillon WP
中科院分区：
文献类型：
--
作者：
Brown JD;Saeed M;Do L;Braz J;Basbaum AI;Iadarola MJ;Wilson DM;Dillon WP
镇痛的一种方法是通过选择性地直接消融疼痛传递神经元或神经末梢来阻断起源部位或沿着外周通路的疼痛。由伤害感受神经元表达的热/辣椒素受体（TRPV 1）是选择性介入镇痛的一个引人注目的靶点，因为它使体感和本体感受神经元保持完整。树脂毒素（RTX）与辣椒素一样，是TRPV 1激动剂，但效力更强。我们将联合收割机RTX介导的灭活与计算机断层扫描（CT）引导的精确递送相结合，以消融猪的外周疼痛纤维。在CT引导下，在腰背根神经节（DRG）周围单侧递送RTX，并且仅向对侧施用载体。在4周的观察期内，动物表现出延迟或不存在对递送至与接受RTX治疗的DRG对应的感觉皮区的红外激光热刺激的戒断反应。通过残疾评分和步态分析评估，运动功能未受损。在治疗后的DRG中，TRPV 1 mRNA表达减少，神经节中的伤害性神经元胞体及其同侧背角中的神经末梢也减少。CT引导精确地将RTX递送到猪的外周疼痛传递部位可能是一种可以定制以阻断患者的一系列临床疼痛状况的方法。
One approach to analgesia is to block pain at the site of origin or along the peripheral pathway by selectively ablating pain-transmitting neurons or nerve terminals directly. The heat/capsaicin receptor (TRPV1) expressed by nociceptive neurons is a compelling target for selective interventional analgesia because it leaves somatosensory and proprioceptive neurons intact. Resiniferatoxin (RTX), like capsaicin, is a TRPV1 agonist but has greater potency. We combine RTX-mediated inactivation with the precision of computed tomography (CT)–guided delivery to ablate peripheral pain fibers in swine. Under CT guidance, RTX was delivered unilaterally around the lumbar dorsal root ganglia (DRG), and vehicle only was administered to the contralateral side. During a 4-week observation period, animals demonstrated delayed or absent withdrawal responses to infrared laser heat stimuli delivered to sensory dermatomes corresponding to DRG receiving RTX treatment. Motor function was unimpaired as assessed by disability scoring and gait analysis. In treated DRG, TRPV1 mRNA expression was reduced, as were nociceptive neuronal perikarya in ganglia and their nerve terminals in the ipsilateral dorsal horn. CT guidance to precisely deliver RTX to sites of peripheral pain transmission in swine may be an approach that could be tailored to block an array of clinical pain conditions in patients.