Resiniferatoxin combined with antidepressants preferentially prolongs sensory/nociceptive block in rat sciatic nerve.
BACKGROUND
Current techniques of peripheral nerve block have major limitations, including lack of differentiation between motor and sensory fibers and potential toxicity of local anesthetics. Recent studies have suggested that a nociceptive-selective nerve block can be achieved via a transient receptor potential vanilloid type 1 activator (capsaicin) along with local anesthetics. We hypothesized that the combination of potent transient receptor potential vanilloid type 1 agonist resiniferatoxin (RTX) and selected antidepressants (amitriptyline, doxepin, and fluoxetine, also potent sodium channel blockers) would produce prolonged and predominantly sensory nerve block.


METHODS
Rats were anesthetized with isoflurane, and 0.2 mL of amitriptyline, doxepin, or fluoxetine was deposited next to the surgically exposed sciatic nerves (n = 8 per group). Some animals received a second injection containing RTX (n = 8 per group). The effect of nerve block was assessed by neurobehavioral tests of the motor function (extensor postural thrust) and the nocifensive reaction (mechanical pinch).


RESULTS
A single application of RTX produced nociceptive-selective sciatic nerve block, whereas antidepressants produced nociceptive and motor block. The combined administration of RTX and antidepressant resulted in a predominantly nociceptive nerve block. Compared with antidepressants or RTX alone, the combination prolonged the nociceptive nerve block more than the motor block.


CONCLUSIONS
The combined application of RTX and antidepressants produced a markedly prolonged nociceptive peripheral nerve block in rat sciatic nerves compared with either agent alone. However, the 2-drug regimen also elicited prolonged blockade of the motor function, although disproportionately less compared with the nociceptive modality, suggesting the existence of nontransient receptor potential vanilloid type 1-mediated mechanisms. The mechanisms through which RTX affects nociceptive signal transduction/transmission have yet to be fully elucidated.
Department of Anesthesiology, Mackay Memorial Hospital, 92 Sec. 2, Zhongshan N. Rd., Taipei 10449, Taiwan. yuchun51@ms22.hinet.net
Yu-Chun
YC
Hung
Suzuko
S
Suzuki
Chun-Jen
CJ
Huang
Chien-Chuan
CC
Chen
Yu-Yen
YY
Pan
Chi-Fei
CF
Wang
Venkatesh
V
Srinavasan
Peter
P
Gerner
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004316:Doxepin / Q000494:pharmacology; D004357:Drug Synergism; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D009407:Nerve Block; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects*; D011984:Sensory Receptor Cells / Q000187:drug effects*
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D004224:Diterpenes; D005473:Fluoxetine; D004316:Doxepin; D000639:Amitriptyline; C024353:resiniferatoxin