title: Effects of Lidocaine, Bupivacaine, and Ropivacaine on Calcitonin Gene-Related Peptide and Substance P Levels in the Incised Rat Skin.
abstract: OBJECTIVE
  To evaluate the effect of 2% lidocaine, 0.5% bupivacaine, and 0.75% ropivacaine on the release of substance P (SP) and calcitonin gene-related peptide (CGRP) in skin wounds.
  
  
  METHODS
  A primary, experimental, analytical, prospective, self-controlled, blinded study.
  
  
  METHODS
  The study is set in a university research center.
  
  
  METHODS
  Twenty-eight Wistar rats were randomly divided into 4 groups: lidocaine, bupivacaine, ropivacaine, and the control. After general anesthesia, a local anesthetic or 0.9% saline (control) was injected subdermally along a 2-cm line on the dorsal midline of each rat; 30 minutes later, an incision (nociceptive stimulus) was made along this line. The animals were euthanized, and skin samples were collected from the center of the incision line and sent for CGRP and SP quantification.
  
  
  METHODS
  Quantification of CGRP and SP by Western blotting.
  
  
  RESULTS
  Substance P levels were similar in the lidocaine and ropivacaine groups but were significantly lower than those of the control group (P = .002); no significant difference in SP levels was found between the bupivacaine and control groups. Procalcitonin gene-related peptide levels were significantly lower in the experimental groups than those in control subjects (P = .009), with no significant differences among the experimental groups. No significant differences in CGRP levels were found among all groups. Lidocaine and ropivacaine inhibited SP release. All 3 local anesthetics inhibited the release of procalcitonin gene-related peptide, but not the release of CGRP in rat skin.
  
  
  CONCLUSIONS
  Lidocaine and ropivacaine may inhibit neurogenic inflammation by biochemical pathways activated by SP, whereas bupivacaine seems to have no influence on this process.
authors.affiliation: Guilherme A. F. Lapin, MD, is a Graduate Student in the Division of Plastic Surgery, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Bernardo Hochman, MD, PhD, is an Affiliate Professor in the Division of Plastic Surgery and the Coordinator of the Sector of Pathologic Scars in that same division at UNIFESP. Jessica R. Maximino, PhD, is a Neuroscience Researcher in the Translational Neurology Unit at the Universidade de São Paulo School of Medicine (USP), São Paulo, Brazil. Gerson Chadi, MD, PhD, is a Professor in the Experimental Neurology Department, Head of the Pathophysiology-LIM45, and Coordinator of the Study Group on Neuroregeneration, all at USP. Lydia M. Ferreira, MD, PhD, is a Professor in the Division of Plastic Surgery at UNIFESP, Researcher IB CNPq (Brazilian National Council for Scientific and Technological Development), Brasília, Federal District, Brazil, and Assistant Coordinator of MED III CAPES (Coordination for the Improvement of Higher Education Personnel), Brasília, Federal District, Brazil.
authors.forename: Guilherme A F
authors.initials: GA
authors.lastname: Lapin
authors.forename: Bernardo
authors.initials: B
authors.lastname: Hochman
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Maximino
authors.forename: Gerson
authors.initials: G
authors.lastname: Chadi
authors.forename: Lydia M
authors.initials: LM
authors.lastname: Ferreira
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D008012:Lidocaine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077212:Ropivacaine; D012867:Skin / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D000072836:Surgical Wound / Q000378:metabolism*
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D013373:Substance P; D000077212:Ropivacaine; D008012:Lidocaine; D015740:Calcitonin Gene-Related Peptide; D002045:Bupivacaine