Unilateral Epidural Targeting of Resiniferatoxin Induces Bilateral Neurolysis of Spinal Nociceptive Afferents.
- Resource Type
- Article
- Authors
- Unger, Mark D; Pleticha, Josef; Steinauer, Joanne; Kanwar, Rahul; Diehn, Felix; LaVallee, Katherine T; Banck, Michaela S; Jones, Bryan; Yaksh, Tony L; Maus, Timothy P; Beutler, Andreas S
- Source
- Pain Medicine. May2019, Vol. 20 Issue 5, p897-906. 10p. 3 Color Photographs, 1 Chart.
- Subject
- *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
- Language
- ISSN
- 1526-2375
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]