{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T14:35:08Z","timestamp":1772634908184,"version":"3.50.1"},"reference-count":16,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2011,12,15]],"date-time":"2011-12-15T00:00:00Z","timestamp":1323907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>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 \u00b5g\/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 \u00b5M and epinephrine 5 \u00b5g\/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P &lt; 0.001) or bupivacaine 0.25% with epinephrine 5 \u00b5g\/mL (P &lt; 0.001). Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 \u00b5g\/mL appear promising for prolonged duration of local anesthesia.<\/jats:p>","DOI":"10.3390\/md9122717","type":"journal-article","created":{"date-parts":[[2011,12,15]],"date-time":"2011-12-15T11:07:44Z","timestamp":1323947264000},"page":"2717-2728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia"],"prefix":"10.3390","volume":"9","author":[{"given":"Charles B.","family":"Berde","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Children\u2019s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umeshkumar","family":"Athiraman","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Children\u2019s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barak","family":"Yahalom","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Children\u2019s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Zurakowski","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Children\u2019s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Corfas","sequence":"additional","affiliation":[{"name":"Departments of Otolaryngology and Neuroscience, Children\u2019s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Bognet","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine, Children\u2019s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2011,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1213\/00000539-199809000-00019","article-title":"A double-blind comparison of ropivacaine, bupivacaine, and mepivacaine during sciatic and femoral nerve blockade","volume":"87","author":"Fanelli","year":"1998","journal-title":"Anesth. Analg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1007\/BF03012398","article-title":"Lumbar plexus and sciatic nerve block for knee arthroplasty: Comparison of ropivacaine and bupivacaine","volume":"45","author":"Greengrass","year":"1998","journal-title":"Can. J. Anaesth."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1213\/00000539-199812000-00019","article-title":"A comparison of 0.5% bupivacaine, 0.5% ropivacaine, and 0.75% ropivacaine for interscalene brachial plexus block","volume":"87","author":"Klein","year":"1998","journal-title":"Anesth. Analg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1213\/ane.0b013e318187c9bb","article-title":"Elastomeric pump reliability in postoperative regional anesthesia: a survey of 430 consecutive devices","volume":"107","author":"Remerand","year":"2008","journal-title":"Anesth. Analg."},{"key":"ref_5","first-page":"830","article-title":"Tetrodotoxin poisoning: a clinical analysis, role of neostigmine and short-term outcome of 53 cases","volume":"48","author":"Chowdhury","year":"2007","journal-title":"Singap. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.toxicon.2003.11.018","article-title":"Paralytic shellfish poisoning: post-mortem analysis of tissue and body fluid samples from human victims in the Patagonia fjords","volume":"43","author":"Garcia","year":"2004","journal-title":"Toxicon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jpainsymman.2007.05.011","article-title":"Tetrodotoxin for moderate to severe cancer pain: A randomized, double blind, parallel design multicenter study","volume":"35","author":"Hagen","year":"2008","journal-title":"J. Pain Symptom Manag."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jpainsymman.2006.11.008","article-title":"An open-label, multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancer-related pain","volume":"34","author":"Hagen","year":"2007","journal-title":"J. Pain Symptom Manag."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/00000542-199807000-00019","article-title":"A re-examination of tetrodotoxin for prolonged duration local anesthesia","volume":"89","author":"Kohane","year":"1998","journal-title":"Anesthesiology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1097\/ALN.0b013e31816c8a48","article-title":"Local myotoxicity from sustained release of bupivacaine from microparticles","volume":"108","author":"Padera","year":"2008","journal-title":"Anesthesiology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1002\/mus.20618","article-title":"Tetrodotoxin for prolonged local anesthesia with minimal myotoxicity","volume":"34","author":"Padera","year":"2006","journal-title":"Muscle Nerve"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.pain.2009.02.020","article-title":"Relief of postoperative pain by local anaesthetic infiltration: Efficacy for major abdominal and orthopedic surgery","volume":"143","author":"Dahl","year":"2009","journal-title":"Pain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1097\/00000542-199504000-00026","article-title":"Neurologic evaluation of the rat during sciatic nerve block with lidocaine","volume":"82","author":"Thalhammer","year":"1995","journal-title":"Anesthesiology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1097\/00000542-200406000-00026","article-title":"Amitriptyline neurotoxicity: dose-related pathology after topical application to rat sciatic nerve","volume":"100","author":"Estebe","year":"2004","journal-title":"Anesthesiology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Statist. Soc. B"},{"key":"ref_16","unstructured":"(SPSS software package for Windows, 2007). SPSS software package for Windows."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/9\/12\/2717\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:58:21Z","timestamp":1760219901000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/9\/12\/2717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,15]]},"references-count":16,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2011,12]]}},"alternative-id":["md9122717"],"URL":"https:\/\/doi.org\/10.3390\/md9122717","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,15]]}}}