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Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw inflammation in rats (Part 1): hyperalgesia, edema, and systemic cytokines.

Publication ,  Journal Article
Beloeil, H; Ababneh, Z; Chung, R; Zurakowski, D; Mulkern, RV; Berde, CB
Published in: Anesthesiology
July 2006

BACKGROUND: Local anesthetics exert antiinflammatory actions. To elucidate potential mechanisms, the authors examined effects of bupivacaine or tetrodotoxin, administered to rats by ipsilateral or contralateral sciatic blockade or systemically, on carrageenan-induced hind paw hyperalgesia, edema, and stimulated cytokine production in circulating blood cells. METHODS: Twelve groups of rats (n = 9-12) received injections in three sites: (1) right or left hind paw (carrageenan or saline), (2) left sciatic block, and (3) systemically (subcutaneously in the upper back). Sciatic and systemic injections were performed with epinephrine plus bupivacaine, tetrodotoxin, or saline; injections were repeated 6 h later. Fifteen hours later, hyperalgesia and/or sensory and motor block were assessed behaviorally, and paw edema was quantified by magnetic resonance imaging. Stimulated production of tumor necrosis factor alpha, interleukin 10, and interleukin 1beta in whole blood cultures was measured by enzyme-linked immunosorbent assay. RESULTS: Either ipsilateral or contralateral sciatic blocks using either bupivacaine or tetrodotoxin reduced carrageenan-induced edema and hyperalgesia. Systemic bupivacaine and tetrodotoxin were ineffective in preventing edema and hyperalgesia. Bupivacaine was effective in suppressing systemic tumor necrosis factor alpha and interleukin 1beta by all three routes, whereas tetrodotoxin was ineffective by all three routes. CONCLUSION: Bupivacaine and tetrodotoxin, via a contralateral or ipsilateral sciatic block, attenuate local inflammatory edema and hyperalgesia induced by hind paw injection of carrageenan in rats. Mechanisms underlying contralateral effects of sciatic blockade remain unexplained. Bupivacaine inhibits carrageenan-evoked systemic cytokine production by a mechanism not shared by tetrodotoxin; this action may involve tetrodotoxin-resistant sodium channels or a variety of non-sodium-channel targets.

Duke Scholars

Published In

Anesthesiology

DOI

ISSN

0003-3022

Publication Date

July 2006

Volume

105

Issue

1

Start / End Page

128 / 138

Location

United States

Related Subject Headings

  • Tetrodotoxin
  • Rats, Sprague-Dawley
  • Rats
  • Male
  • Inflammation
  • Hindlimb
  • Edema
  • Drug Therapy, Combination
  • Carrageenan
  • Bupivacaine
 

Citation

APA
Chicago
ICMJE
MLA
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Beloeil, H., Ababneh, Z., Chung, R., Zurakowski, D., Mulkern, R. V., & Berde, C. B. (2006). Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw inflammation in rats (Part 1): hyperalgesia, edema, and systemic cytokines. Anesthesiology, 105(1), 128–138. https://doi.org/10.1097/00000542-200607000-00022
Beloeil, Hélène, Zaid Ababneh, Richard Chung, David Zurakowski, Robert V. Mulkern, and Charles B. Berde. “Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw inflammation in rats (Part 1): hyperalgesia, edema, and systemic cytokines.Anesthesiology 105, no. 1 (July 2006): 128–38. https://doi.org/10.1097/00000542-200607000-00022.
Beloeil H, Ababneh Z, Chung R, Zurakowski D, Mulkern RV, Berde CB. Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw inflammation in rats (Part 1): hyperalgesia, edema, and systemic cytokines. Anesthesiology. 2006 Jul;105(1):128–38.
Beloeil, Hélène, et al. “Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw inflammation in rats (Part 1): hyperalgesia, edema, and systemic cytokines.Anesthesiology, vol. 105, no. 1, July 2006, pp. 128–38. Pubmed, doi:10.1097/00000542-200607000-00022.
Beloeil H, Ababneh Z, Chung R, Zurakowski D, Mulkern RV, Berde CB. Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw inflammation in rats (Part 1): hyperalgesia, edema, and systemic cytokines. Anesthesiology. 2006 Jul;105(1):128–138.

Published In

Anesthesiology

DOI

ISSN

0003-3022

Publication Date

July 2006

Volume

105

Issue

1

Start / End Page

128 / 138

Location

United States

Related Subject Headings

  • Tetrodotoxin
  • Rats, Sprague-Dawley
  • Rats
  • Male
  • Inflammation
  • Hindlimb
  • Edema
  • Drug Therapy, Combination
  • Carrageenan
  • Bupivacaine