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neurogenic inflammation, neuropeptides, substance P, calcitonin gene-related peptide, local anesthetics



  1. Lapin, Guilherme A. F. MD
  2. Hochman, Bernardo MD, PhD
  3. Maximino, Jessica R. PhD
  4. Chadi, Gerson MD, PhD
  5. Ferreira, Lydia M. MD, PhD


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.


DESIGN: A primary, experimental, analytical, prospective, self-controlled, blinded study.


SETTING: The study is set in a university research center.


INTERVENTIONS: 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.


MAIN OUTCOME MEASURES: 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.