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

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.

• Authors: Jacob D Brown, Maythem Saeed, Loi Do, Joao Braz, Allan I Basbaum, Michael J Iadarola, David M Wilson, William P Dillon
• Journal: Science translational medicine (Sci Transl Med) Vol. 7 Issue 305 Pg. 305ra145 (Sep 16 2015) ISSN: 1946-6242 [Electronic] United States
• PMID: 26378245 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Association for the Advancement of Science.

Chemical References

• Diterpenes
• RNA, Messenger
• TRPV Cation Channels
• TRPV1 receptor
• resiniferatoxin

Topics

• Animals
• Behavior, Animal
• Diterpenes (administration & dosage)
• Female
• Ganglia (pathology)
• Ganglia, Spinal (diagnostic imaging)
• Gene Expression Profiling
• Hot Temperature
• Lasers
• Lumbar Vertebrae (pathology)
• Microscopy, Fluorescence
• Motor Skills (drug effects)
• Neurons (metabolism)
• Pain (drug therapy)
• RNA, Messenger (metabolism)
• Swine
• TRPV Cation Channels (agonists)
• Tomography, X-Ray Computed