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Transient Heat Hyperalgesia During Resolution of Ropivacaine Sciatic Nerve Block in the Rat
  1. Lavinia M. Kolarczyk, MD* and
  2. 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. Veterans Administration Pittsburgh Health System, Pittsburgh, PA.
  1. Address correspondence to: Lavinia M. Kolarczyk, MD, Department of Anesthesiology, University of Pittsburgh School of Medicine, A-1305 Scaife Hall, Pittsburgh, PA 15213 (e-mail: kolarczyklm{at}


Background: Preliminary studies using perineural sciatic ropivacaine in rat demonstrated unexpected heat hyperalgesia after block resolution. To better characterize the time course relative to mechanical anesthesia-analgesia, we tested the hypothesis that ropivacaine 0.5% leads to transient heat hyperalgesia in rats independent of mechanical nociception. We also evaluated functional toxicity (eg, long-term hyperalgesia and/or tactile allodynia 2 weeks after injection).

Methods: Under surgical exposure, left sciatic nerve block was performed in 2 groups of adult male rats-ropivacaine (200 μL, 5 mg/mL; n = 14) versus vehicle (n = 11). The efficacy and duration of block were assessed with serial heat, mechanical (Randall-Selitto testing), and tactile (von Frey-like monofilaments) tests; motor-proprioceptive (rotating rod) and sedation tests were used at 1 and 7 hrs after injection. The presence of nerve injury was assessed by repeating the heat, tactile, and motor tests 12 to 14 days after injection.

Results: Ropivacaine-induced anesthesia was fully manifest at 1 hr after injection. At 3 hrs after injection, heat hypersensitivity was present in the setting of resolved mechanical analgesia. All behavioral measures returned to baseline by 2 weeks after injection. There was no evidence of (i) behavioral sedation, (ii) persistent changes in heat or mechanical sensitivity, or (iii) persistent changes in proprioceptive-motor function at 12 to 14 days after injection.

Conclusions Ropivacaine 0.5% induces transient heat hyperalgesia in the setting of resolved mechanical analgesia, further suggestive of modality and/or nociceptive fiber specificity. Whether this finding partially translates to "rebound pain" after patients' nerve blocks wear off requires further study.

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  • This research was supported by the following: K01DA025146 (Dr Williams) and 1 UL1 RR024153 (Dr Williams), from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Regarding 1 UL1 RR024153, its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at Information on Re-engineering the Clinical Research Enterprise can be obtained from A special grant from the Office of the Senior Vice Chancellor for the Health Sciences, University of Pittsburgh is also acknowledged, as is additional material support from (i) University of Pittsburgh Department of Anesthesiology, and (ii) Pittsburgh Center for Pain Research. Dr Williams received consulting fees from B.Braun USA (2010); B.Braun USA was not involved with the design or conduct of this study, and this manuscript or its contents were not made available to B.Braun USA prior to publication.

  • This research was presented as a poster discussion at the 2010 American Society of Anesthesiologists Annual Meeting in San Diego, CA, on October 17, 2010.