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


OBJECTIVE
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 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).


RESULTS
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).


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.
Department of Anesthesiology and Pain Medicine, University of Washington Medical Center, Seattle, WA 98195, USA.
Mathieu
M
Méleine
Cyril
C
Rivat
Emilie
E
Laboureyras
Alex
A
Cahana
Philippe
P
Richebé
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D005283:Fentanyl / Q000008:administration & dosage*; D006930:Hyperalgesia / Q000517:prevention & control*; D008297:Male; D009407:Nerve Block; D017288:Pain Threshold; D010149:Postoperative Pain / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve; D013315:Stress, Psychological / Q000150:complications*
D000701:Analgesics, Opioid; D005283:Fentanyl