ArticleJournal of inflammation research2008
Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite.
Article in Journal of inflammation research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 80 citations in OpenAlex.
- Evaluating the effect of using anti-stress balls as a distraction technique in reducing pain during inferior alveolar nerve block injection: a randomized clinical trial.Clinical oral investigations · 2023Trial
- HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the phase 3 EPOCH 2 study.Hernia : the journal of hernias and abdominal wall surgery · 2019Trial
- Effectiveness of the addition of Lidocaine to a hemostatic, bioresorbable putty in the treatment of iliac crest donor site pain.BMC musculoskeletal disorders · 2014Trial
- Comparative evaluation of supplemental buccal infiltration adjuncts for enhancing inferior alveolar nerve block in symptomatic irreversible pulpitis: A randomized double-blind clinical study.Journal of conservative dentistry and endodontics · 2026Article
- Spatiotemporal dynamics of local anesthetic diffusion in nerve revealed by a 2D computational model.Biophysical journal · 2025Article
- AT-17 redefines local anesthetics by targeting mitochondrial apoptosis.Acta pharmaceutica Sinica. B · 2025Article
- Effect of intraperitoneal bupivacaine vs magnesium sulfate on early postoperative outcomes after laparoscopic sleeve gastrectomy: a randomized clinical trial.Perioperative medicine (London, England) · 2025Article
- Nanoparticle-Reinforced Hydrogel with a Well-Defined Pore Structure for Sustainable Drug Release and Effective Wound Healing.ACS applied bio materials · 2025Article
- Application of articaine in endoscopic endonasal dacryocystorhinostomy: a retrospective study.Frontiers in medicine · 2024Article
- A Review of the Lidocaine in the Perioperative Period.Journal of personalized medicine · 2023Review
- Improved Local Anesthesia at Inflamed Tissue Using the Association of Articaine and Copaiba Oil in Avocado Butter Nanostructured Lipid Carriers.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Transient cutaneous hypomelanosis after cryoanesthesia.Dermatology reports · 2023Article
- Does a New Modification of the Two-Step Injection Technique for Inferior Alveolar Nerve Block Reduce Pain Compared to the Conventional Technique? A Randomized Clinical Trial.International journal of dentistry · 2023Article
- Superficial cervical plexus block in Emergency Departments: rationale for its use in incision and drainage of neck skin abscesses.Internal and emergency medicine · 2022Article
- Cardiovascular Response of Aged Outpatients With Systemic Diseases During Tooth Extraction: A Single-Center Retrospective Observational Study.Frontiers in public health · 2022Observational
- Comparative Analysis of Different Local Anesthetic Solutions Available in Market: An In Vitro and Clinical Study.European journal of dentistry · 2021Article
- Effects of treatment with local anesthetics on RANKL expression in MG63 and PDL cells.Journal of dental sciences · 2021Article
- Nanotherapeutic-directed approaches to analgesia.Trends in pharmacological sciences · 2021Review
- Electrochemical deposition of highly hydrophobic perfluorinated polyaniline film for biosensor applications.RSC advances · 2021Article
- Response to the letter to the editor by Hafer and Johnson concerning 'Mechanism of action of HTX-011: a novel, extended-release, dual-acting local anesthetic formulation for postoperative pain'.Regional anesthesia and pain medicine · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The presence of inflammation decreases local anesthetic efficacy, especially in dental anesthesia. Although inflammatory acidosis is most frequently cited as the cause of such clinical phenomena, this has not been experimentally proved. We verified the acidosis mechanism by studying the drug and membrane lipid interaction under acidic conditions together with proposing an alternative hypothesis. Liposomes and nerve cell model membranes consisting of phospholipids and cholesterol were treated at different pH with lidocaine, prilocaine and bupivacaine (0.05%-0.2%, w/v). Their membrane-interactive potencies were compared by the induced-changes in membrane fluidity. Local anesthetics fluidized phosphatidylcholine membranes with the potency being significantly lower at pH 6.4 than at pH 7.4 (p < 0.01), supporting the acidosis theory. However, they greatly fluidized nerve cell model membranes even at pH 6.4 corresponding to inflamed tissues, challenging the conventional mechanism. Local anesthetics acted on phosphatidylserine liposomes, as well as nerve cell model membranes, at pH 6.4 with almost the same potency as that at pH 7.4, but not on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin liposomes. Since the positively charged anesthetic molecules are able to interact with nerve cell membranes by ion-paring with anionic components like phosphatidylserine, tissue acidosis is not essentially responsible for the local anesthetic failure associated with inflammation. The effects of local anesthetics on nerve cell model membranes were inhibited by treating with peroxynitrite (50 μM), suggesting that inflammatory cells producing peroxynitrite may affect local anesthesia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.