Research ArticlePain

CT-guided injection of a TRPV1 agonist around dorsal root ganglia decreases pain transmission in swine

Science Translational Medicine  16 Sep 2015:
Vol. 7, Issue 305, pp. 305ra145
DOI: 10.1126/scitranslmed.aac6589

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Improved pain control with a spicy chili pepper variant

Chronic severe pain can be agonizing, and methods to control it are often inadequate or limited by side effects. Brown et al. used a CT scanner to guide needles through the skin of swine directly to pain-transmitting nerve fibers. Through these needles, they injected resiniferatoxin, which is a very powerful variant of capsaicin, the spicy ingredient in chili peppers. This drug is toxic to cells that carry its receptor (TRPV1), which are almost exclusively pain-transmitting neurons. This enabled the authors to selectively block pain transmission in pigs without affecting “bystander” nerves carrying other sensory information.

Abstract

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.

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