title: Local anesthetics differentially inhibit sympathetic neuron-mediated and C fiber-mediated synovial neurogenic plasma extravasation.
abstract: Local anesthetics are used for local irrigation after many types of operations. However, recent evidence of toxic effects of local anesthetics at large concentrations during continuous administration suggests an advantage of using decreased local anesthetic concentrations for irrigation solutions. In this study, we determined whether smaller concentrations of local anesthetics may maintain an antiinflammatory and, therefore, analgesic effect without the risk of possible toxicity. Lidocaine and bupivacaine were studied for their ability to inhibit both components of neurogenic inflammation-C fiber-mediated and sympathetic postganglionic neuron (SPGN)-mediated inflammation-in the rat knee joint. Intraarticular lidocaine 0.02% reduced 5-hydroxytryptamine (5-HT)-induced (SPGN-mediated) plasma extravasation (PE) by 35%, and further decreases were obtained by perfusing larger concentrations of lidocaine. Intraarticular bupivacaine 0.025% inhibited 5-HT-induced PE by 60%, and a 95% inhibition was obtained with bupivacaine 0.05%. Larger local anesthetic concentrations were necessary to inhibit C fiber-mediated PE than those required to inhibit SPGN-mediated PE. Lidocaine 0.4% was required to reduce mustard oil-induced PE by 60%. Lidocaine 2% inhibited mustard oil-induced PE to baseline levels. Bupivacaine 0.1% was required for an 80% reduction of PE. Bupivacaine 0.25% inhibited mustard oil-induced PE to baseline levels. Our results demonstrate differential effects of local anesthetics on SPGN- and C fiber-mediated PE but confirm the concept of using smaller concentrations of local anesthetics to achieve inhibition of postoperative inflammation.
  
  
  CONCLUSIONS
  Local anesthetic wound irrigation is often used to treat postoperative surgical pain. Large concentrations of local anesthetics are usually used, and these concentrations may have possible neurotoxic and myotoxic effects. Our results demonstrate antiinflammatory effects of lidocaine and bupivacaine at concentrations smaller than used clinically.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California-San Francisco, San Francisco, California.
authors.forename: Christian
authors.initials: C
authors.lastname: Pietruck
authors.forename: Stefan
authors.initials: S
authors.lastname: Grond
authors.forename: Guo-Xi
authors.initials: GX
authors.lastname: Xie
authors.forename: Pamela P
authors.initials: PP
authors.lastname: Palmer
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007596:Joints / Q000187:drug effects* / Q000294:innervation*; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009149:Mustard Plant; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D010938:Plant Oils; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects*; D013582:Synovial Fluid / Q000187:drug effects*
chemical_list: D000779:Anesthetics, Local; D010936:Plant Extracts; D010938:Plant Oils; D012701:Serotonin; D008012:Lidocaine; C027793:mustard oil; D002045:Bupivacaine