Sciatic nerve block with resiniferatoxin: an electron microscopic study of unmyelinated fibers in the rat.
BACKGROUND
Perineural administration of the naturally occurring vanilloids (capsaicin, resiniferatoxin [RTX]) produces selective nociceptive blockade. Studies using perineural vanilloids in high concentrations suggest that they can cause a degeneration of unmyelinated fibers. However, electron microscopic studies of local vanilloid toxicity produced conflicting outcomes. In the present study, we sought to determine whether RTX-induced reversible sciatic nerve block results in the degenerative changes of unmyelinated fibers.


METHODS
In rat experiments, RTX was administered percutaneously at the sciatic nerve. The effect of RTX was monitored by measuring the rat's response to noxious heat. The sciatic nerves were removed 48 h after the blockade initiation. Quantitative electron microscopic evaluation of the unmyelinated fibers was performed in three groups of animals: RTX 0.0001% (0.1 microg), RTX 0.001% (1 microg), and control (RTX vehicle, 0.1 mL).


RESULTS
Cross-sections of the sciatic nerve 48 h after the initiation of RTX-induced reversible nerve blockade appeared essentially normal. One rarely observed finding was the irregularly compacted membranous deposits in the unmyelinated axons. The frequency of this finding was approximately one per thousand fibers with both concentrations of RTX.


CONCLUSIONS
The results of the study suggest that a selective and long-lasting sciatic nerve block (up to 2 wk) can be provided by RTX without any significant damage to the unmyelinated nerve fibers.
Kissin
Igor
I
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. kissin@zeus.bwh.harvard.edu
Freitas
Cristina F
CF
Mulhern
Howard L
HL
DeGirolami
Umberto
U
D000700:Analgesics / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D004224:Diterpenes / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D008297:Male; D008854:Microscopy, Electron; D009407:Nerve Block / Q000379:methods*; D009410:Nerve Degeneration / Q000139:chemically induced; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000648:ultrastructure; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000648:ultrastructure
D000700:Analgesics; D004224:Diterpenes; C024353:resiniferatoxin