Resiniferatoxin combined with antidepressants preferentially prolongs sensory/nociceptive block in rat sciatic nerve

Yu Chun Hung, Suzuko Suzuki, Chun Jen Huang, Chien Chuan Chen, Yu Yen Pan, Chi-Fei Wang, Venkatesh Srinavasan, Peter Gerner

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)207-213
Number of pages7
JournalAnesthesia and analgesia
Volume111
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1

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Nerve Block
Sciatic Nerve
Antidepressive Agents
Doxepin
Amitriptyline
Fluoxetine
Local Anesthetics
Peripheral Nerves
Sodium Channel Blockers
resiniferatoxin
Isoflurane
Capsaicin
Signal Transduction
Injections
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

Hung, Yu Chun ; Suzuki, Suzuko ; Huang, Chun Jen ; Chen, Chien Chuan ; Pan, Yu Yen ; Wang, Chi-Fei ; Srinavasan, Venkatesh ; Gerner, Peter. / Resiniferatoxin combined with antidepressants preferentially prolongs sensory/nociceptive block in rat sciatic nerve. In: Anesthesia and analgesia. 2010 ; Vol. 111, No. 1. pp. 207-213.
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abstract = "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.",
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Resiniferatoxin combined with antidepressants preferentially prolongs sensory/nociceptive block in rat sciatic nerve. / Hung, Yu Chun; Suzuki, Suzuko; Huang, Chun Jen; Chen, Chien Chuan; Pan, Yu Yen; Wang, Chi-Fei; Srinavasan, Venkatesh; Gerner, Peter.

In: Anesthesia and analgesia, Vol. 111, No. 1, 01.01.2010, p. 207-213.

Research output: Contribution to journalArticle

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AU - Hung, Yu Chun

AU - Suzuki, Suzuko

AU - Huang, Chun Jen

AU - Chen, Chien Chuan

AU - Pan, Yu Yen

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AU - Gerner, Peter

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