Tetrodotoxin-bupivacaine-epinephrine combinations for prolonged local anesthesia

Mar Drugs. 2011 Dec;9(12):2717-2728. doi: 10.3390/md9122717. Epub 2011 Dec 15.

Abstract

Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX) with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL) solutions, with or without epinephrine 5 µg/mL (1:200,000) in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001) or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001). Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia.

Keywords: bupivacaine; epinephrine; local anesthesia; sciatic blockade; tetrodotoxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia, Local*
  • Anesthetics, Local / pharmacology*
  • Animals
  • Behavior, Animal / drug effects
  • Bupivacaine / administration & dosage*
  • Epinephrine / administration & dosage*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / pathology
  • Sciatic Nerve / physiology
  • Tetrodotoxin / administration & dosage*

Substances

  • Anesthetics, Local
  • Tetrodotoxin
  • Bupivacaine
  • Epinephrine