Unilateral Epidural Targeting of Resiniferatoxin Induces Bilateral Neurolysis of Spinal Nociceptive Afferents.

Pain Med 2019 05;20(5):897-906

Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1093/pm/pny276DOI Listing
May 2019
2 Reads

Publication Analysis

Top Keywords

spinal cord
12
cord substance
8
substance immunostaining
8
bilateral ablation
8
pre-injected contrast
8
distribution pre-injected
8
contrast distribution
8
substance
5
contrast
5
spinal
5
animals development
4
contrastconclusions periganglionic
4
development neurological
4
injection well
4
well tolerated
4
periganglionic resiniferatoxin/tween80
4
pre-injected contrastconclusions
4
unilateral
4
tolerated animals
4
uncorrelated anatomical
4

Similar Publications