Unilateral Epidural Targeting of Resiniferatoxin Induces Bilateral Neurolysis of Spinal Nociceptive Afferents.
| Title: | Unilateral Epidural Targeting of Resiniferatoxin Induces Bilateral Neurolysis of Spinal Nociceptive Afferents. |
|---|---|
| Authors: | Unger, Mark D1, Pleticha, Josef2, Steinauer, Joanne3, Kanwar, Rahul1, Diehn, Felix4, LaVallee, Katherine T5, Banck, Michaela S1, Jones, Bryan6, Yaksh, Tony L3, Maus, Timothy P4 beutler.andreas@mayo.edu, Beutler, Andreas S1 |
| Source: | Pain Medicine. May2019, Vol. 20 Issue 5, p897-906. 10p. 3 Color Photographs, 1 Chart. |
| Subject Terms: | *ANIMAL experimentation, *COMPUTED tomography, *DIAGNOSTIC imaging, *DRUG delivery systems, *FLUOROSCOPY, *GUMS & resins, *IMMUNOHISTOCHEMISTRY, *COMPUTERS in medicine, *NOCICEPTORS, *SWINE, *PHYTOCHEMICALS, *CONTRAST media, *NEURAL pathways, *EPIDURAL injections |
| Abstract: | Objective This study modeled image-guided epidural drug delivery to test whether intraprocedural distribution of pre-injected contrast reliably predicts the neuroanatomical reach of resiniferatoxin-mediated nociceptive neurolysis. Methods Swine (N = 12) received unilateral L4-S2 computed tomography fluoroscopy injections by a blinded neuroradiologist; 0.25 mL of contrast was pre-injected to confirm dorsal periganglionic targeting, followed by a 0.5-mL injection of 5 µg of resiniferatoxin/Tween80 or vehicle control. Epidural contrast distribution was graded according to maximum medial excursion. Spinal cord substance P immunostaining quantified the magnitude and anatomical range of resiniferatoxin activity. Results Periganglionic injection was well tolerated by all animals without development of neurological deficits or other complications. Swine were a suitable model of human clinical spinal intervention. The transforaminal approach was used at all L4 and 50% of L5 segments; the remaining segments were approached by the interlaminar route. All injections were successful with unilateral contrast distribution for all resiniferatoxin injections (N = 28). Immunohistochemistry showed bilateral ablation of substance P+ fibers entering the spinal cord of all resiniferatoxin-treated segments. The intensity of substance P immunostaining in treated segments fell below the lower 99% confidence interval of controls, defining the knockout phenotype. Substance P knockout occurred over a narrow range and was uncorrelated to the anatomical distribution of pre-injected contrast. Conclusions Periganglionic resiniferatoxin/Tween80 induced bilateral ablation of spinal cord substance P despite exclusively unilateral targeting. These data suggest that the location of pre-injected contrast is an imperfect surrogate for the neuroanatomical range of drugs delivered to the dorsal epidural compartment that may fail to predict contralateral drug effects. [ABSTRACT FROM AUTHOR] |
| Copyright of Pain Medicine is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Academic Search Complete |
Be the first to leave a comment!