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

Authors :
Allan I. Basbaum
Michael J. Iadarola
Maythem Saeed
William P. Dillon
Loi Do
David M. Wilson
Joao M. Braz
Jacob D. Brown
Source :
Science translational medicine, vol 7, iss 305
Publication Year :
2015
Publisher :
American Association for the Advancement of Science (AAAS), 2015.

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.

Details

ISSN :
19466242 and 19466234
Volume :
7
Database :
OpenAIRE
Journal :
Science Translational Medicine
Accession number :
edsair.doi.dedup.....3ac733553abeeabaf97f1663f9dc02aa
Full Text :
https://doi.org/10.1126/scitranslmed.aac6589