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Effect of Adjuvant Drugs on the Action of Local Anesthetics in Isolated Rat Sciatic Nerves
  1. Eser Yilmaz-Rastoder, MS*,,
  2. Michael S. Gold, PhD*,,
  3. Karen A. Hough, AS, CVT, RLAT*,,
  4. G.F. Gebhart, PhD*, and
  5. Brian A. Williams, MD, MBA*,,
  1. From the *Department of Anesthesiology and
  2. Center for Pain Research, University of Pittsburgh School of Medicine; and
  3. VA Pittsburgh Health System, Pittsburgh, PA.
  1. Address correspondence to: Brian A. Williams, MD, MBA, W-1403 BST-WR, Department of Anesthesiology, Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15261 (e-mail: williamsba{at}


Background and Objectives There is increasing clinical use of adjuvant drugs to prolong the duration of local anesthetic–induced block of peripheral nerves. However, the mechanistic understanding regarding drug interactions between these compounds in the periphery is quite limited. Accordingly, we undertook this study to determine whether selected adjuvant drugs are efficacious in blocking action potential propagation in peripheral nerves at concentrations used clinically and whether these drugs influence peripheral nerve block produced by local anesthetics.

Methods Isolated rat sciatic nerves were used to assess (1) the efficacy of buprenorphine, clonidine, dexamethasone, or midazolam, alone and in combination, on action potential propagation; and (2) their influence on the blocking actions of local anesthetics ropivacaine and lidocaine. Compound action potentials (CAPs) from A- and C-fibers were studied before and after drug application.

Results At estimated clinical concentrations, neither buprenorphine nor dexamethasone affected either A- or C-waves of the CAP. Clonidine produced a small but significant attenuation of the C-wave amplitude. Midazolam attenuated both A- and C-wave amplitudes, but with greater potency on the C-wave. The combination of clonidine, buprenorphine, and dexamethasone had no influence on the potency or duration of local anesthetic– or midazolam-induced block of A- and C-waves of the CAP.

Conclusions These results suggest that the reported clinical efficacy of clonidine, buprenorphine, and dexamethasone influences the actions of local anesthetics via indirect mechanisms. Further identification of these indirect mechanisms may enable the development of novel approaches to achieve longer-duration, modality-specific peripheral nerve block.

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  • This research is supported by a Department of Defense grant (OR090012) to Drs. Williams, Gold, and Gebhart. The article review by Department of Defense grant coprincipal investigator Chester C. Buckenmaier, III, MD (Walter Reed Army Medical Center), is also acknowledged.

  • The authors declare no conflicts of interest.