Sciatic Nerve Block Fails in Preventing the Development of Late Stress-Induced Hyperalgesia When High-Dose Fentanyl Is Administered Perioperatively in Rats

Abstract

: Sciatic nerve block fails in preventing the development of late stress-induced hyperalgesia (SIH) when high-dose fentanyl is administered perioperatively in rats. 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. Experiment 1 evaluated the effects of D0 RA on hyperalgesia after incision and on the variations of nociceptive threshold (NT) after non-nociceptive environmental stress (NNES) at D10. 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 D0 RA (4 injections) on NT variations after surgery (D1-D10) and after stress (D10) in rats treated with fentanyl at the time of surgery (FI and FIMSR groups). Postoperative hyperalgesia lasted for 7, 4, and 2 days for groups I, ISSR, and IMSR, respectively. Non-nociceptive environmental stress at D10 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 D1 and D2 (Dunnett, P < 0.05), but no difference was shown from D3 to D10 (Dunnett, P > 0.05). Hyperalgesic indices calculated for FI and FIMSR groups after NNES at D10 did no show any significant difference (Dunnett, P > 0.05). 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.