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Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia
Department of Anesthesiology, Perioperative and Pain Medicine, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
Departments of Otolaryngology and Neuroscience, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
* Author to whom correspondence should be addressed.
Received: 9 October 2011; in revised form: 18 November 2011 / Accepted: 21 November 2011 / Published: 15 December 2011
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: tetrodotoxin; bupivacaine; epinephrine; local anesthesia; sciatic blockade
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Berde, C.B.; Athiraman, U.; Yahalom, B.; Zurakowski, D.; Corfas, G.; Bognet, C. Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia. Mar. Drugs 2011, 9, 2717-2728.
Berde CB, Athiraman U, Yahalom B, Zurakowski D, Corfas G, Bognet C. Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia. Marine Drugs. 2011; 9(12):2717-2728.
Berde, Charles B.; Athiraman, Umeshkumar; Yahalom, Barak; Zurakowski, David; Corfas, Gabriel; Bognet, Christina. 2011. "Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia." Mar. Drugs 9, no. 12: 2717-2728.