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Sciatic Nerve Block Fails in Preventing the Development of Late Stress-Induced Hyperalgesia When High-Dose Fentanyl Is Administered Perioperatively in Rats
  1. Mathieu Méleine, MS,
  2. Cyril Rivat, PhD*,
  3. Emilie Laboureyras, MS,
  4. Alex Cahana, MD, DAAPM, FIPP, MAS* and
  5. Philippe Richebé, MD, PhD*
  1. From the *Department of Anesthesiology and Pain Medicine, University ofWashington Medical Center, Seattle, WA; and
  2. University of Bordeaux, CNRS, INCIA UMR 5287, Bordeaux, France.
  1. Address correspondence to: Philippe Richebé, MD, PhD, Department of Anesthesiology and Pain Medicine, University of Washington Medical Center, Campus Box 356540, 1959 NE Pacific St, Seattle, WA 98195-6540 (e-mail: prichebe{at}


Sciatic nerve block fails in preventing the development of late stress-induced hyperalgesia (SIH) when high-dose fentanyl is administered perioperatively in rats.

Background and Objectives The aim of our study was to evaluate the effect of regional anesthesia (RA) on hyperalgesia and long-term pain vulnerability after surgery in rats exposed or not to high doses of fentanyl intraoperatively.

Methods Experiment 1 evaluated the effects of D 0 RA on hyperalgesia after incision and on the variations of nociceptive threshold (NT) after non-nociceptive environmental stress (NNES) at D 10. Four groups were compared: control K1 (saline in sciatic nerve catheter, no plantar surgery), I (incision: saline in sciatic nerve catheter and plantar surgery), ISSR (incision–single-shot ropivacaine: single-shot ropivacaine, plantar surgery), and IMSR (incision–multiple-shot ropivacaine: 1 shot of ropivacaine, plantar surgery, and then 3 more ropivacaine injections every 2 h). Experiment 2 evaluated the effects of D 0 RA (4 injections) on NT variations after surgery (D 1D 10) and after stress (D 10) in rats treated with fentanyl at the time of surgery (FI and FIMSR groups).

Results Postoperative hyperalgesia lasted for 7, 4, and 2 days for groups I, ISSR, and IMSR, respectively. Non-nociceptive environmental stress at D 10 showed analgesia during stress in K1 (Dunnett, P < 0.05). Poststress area of hyperalgesia showed that I group developed greater hyperalgesia after NNES than ISSR and IMSR did (Mann-Whitney, P < 0.05). In experiment 2 in the FIMSR group, NT was significantly higher at postoperative D 1 and D 2 (Dunnett, P < 0.05), but no difference was shown from D 3 to D 10 (Dunnett, P > 0.05). Hyperalgesic indices calculated for FI and FIMSR groups after NNES at D 10 did no show any significant difference (Dunnett, P > 0.05).

Conclusions Perioperative use of long-lasting RA reduced both acute postoperative hyperalgesia and the development of long-term pain vulnerability. However, high doses of fentanyl for intraoperative analgesia induce central sensitization that cannot be reversed by using long-lasting RA.

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  • Mathieu Méleine is a PhD student at Université d’Auvergne, INSERM UMR1107, Pharmacologie Fondamentale et Clinique de la Douleur, Faculté de Médecine, 63000 Clermont-Ferrand, France.

  • The authors did not receive financial support for this study.