4.8 Article

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

Journal

SCIENCE TRANSLATIONAL MEDICINE
Volume 7, Issue 305, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aac6589

Keywords

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Funding

  1. Radiological Society of North America, Research and Education Foundation: Resident Research Grant [RR1411]
  2. Seed Grant from Department of Radiology and Biomedical Imaging, University of California, San Francisco [14 -03]
  3. NIH [R01 CA166766, DA29204]
  4. NIH T32 Post-doctoral Training Grant
  5. [NS14627]

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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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