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 ¼ 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 mg 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 ¼ 28). Immunohistochemistry showed bilateral ablation of substance Pþ 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 897-906 |
| Number of pages | 10 |
| Journal | Pain Medicine (United States) |
| Volume | 20 |
| Issue number | 5 |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- Computed Tomography Fluoroscopy
- Epidural Contrast
- Large Animal Model
- Nociceptive Neurolysis
- Periganglionic
- Resiniferatoxin
ASJC Scopus subject areas
- Clinical Neurology
- Anesthesiology and Pain Medicine
Cite this
Unilateral epidural targeting of resiniferatoxin induces bilateral neurolysis of spinal nociceptive afferents. / Unger, Mark D.; Pleticha, Josef; Steinauer, Joanne; Kanwar, Rahul; Diehn, Felix; LaVallee, Katherine T.; Banck, Michaela S.; Jones, Bryan; Yaksh, Tony L.; Maus, Timothy; Beutler, Andreas S.
In: Pain Medicine (United States), Vol. 20, No. 5, 01.01.2019, p. 897-906.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Unilateral epidural targeting of resiniferatoxin induces bilateral neurolysis of spinal nociceptive afferents
AU - Unger, Mark D.
AU - Pleticha, Josef
AU - Steinauer, Joanne
AU - Kanwar, Rahul
AU - Diehn, Felix
AU - LaVallee, Katherine T.
AU - Banck, Michaela S.
AU - Jones, Bryan
AU - Yaksh, Tony L.
AU - Maus, Timothy
AU - Beutler, Andreas S
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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 ¼ 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 mg 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 ¼ 28). Immunohistochemistry showed bilateral ablation of substance Pþ 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.
AB - 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 ¼ 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 mg 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 ¼ 28). Immunohistochemistry showed bilateral ablation of substance Pþ 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.
KW - Computed Tomography Fluoroscopy
KW - Epidural Contrast
KW - Large Animal Model
KW - Nociceptive Neurolysis
KW - Periganglionic
KW - Resiniferatoxin
UR - http://www.scopus.com/inward/record.url?scp=85058142402&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058142402&partnerID=8YFLogxK
U2 - 10.1093/pm/pny276
DO - 10.1093/pm/pny276
M3 - Article
C2 - 30590777
AN - SCOPUS:85058142402
VL - 20
SP - 897
EP - 906
JO - Pain Medicine
JF - Pain Medicine
SN - 1526-2375
IS - 5
ER -