The role of p38MAPK activation in spinal dorsal horn in remifentanil-induced postoperative hyperalgesia in rats.
OBJECTIVE
Remifentanil may induce hyperalgesia. Recent studies implicate a close relationship between post-surgical hyperalgesia and phosphorylation and activation of p38 mitogen-activated protein kinase (p38MAPK) in the spinal microglia. This study aimed to investigate whether the combination of post-surgical and remifentanil-induced hyperalgesia worsens post-operative pain and whether phosphorylated p38MAPK (phospho-p38MAPK) in the spinal dorsal horn in rats is involved in remifentanil-induced postoperative hyperalgesia.


METHODS
Sprague-Dawley rats were randomly divided into six groups: control, incision only, remifentanil only, remifentanil + incision, remifentanil + incision + SB203580, and remifentanil + incision + DMSO. The p38MAPK inhibitor SB203580 and DMSO were injected intrathecally. A right plantar surgical incision was performed in the incision groups, and remifentanil was infused for 60 min in the remifentanil groups. Mechanical paw withdrawal threshold (PWT) and thermal paw withdrawal latency (PWL) of the bilateral hind paws were measured and the number of phospho-p38MAPK-positive cells in rat spinal dorsal horn sections was counted.


RESULTS
Intravenous remifentanil infusion decreased bilateral plantar PWL values from 1 h to 3 days after surgery, however there was no additive effect with incision-induced values. There was a significant increase in the number of dorsal horn phospho-p38MAPK-positive cells in the remifentanil + incision group compared to the incision group, but no increase in the number of these cells when remifentanil was given alone. Intrathecal pretreatment with SB203580 attenuated remifentanil + incision-induced postoperative hyperalgesia and significantly reduced activation of phospho-p38MAPK in spinal dorsal horn.


CONCLUSIONS
Incision-induced and remifentanil-induced increases in hyperalgesia were not additive when incision and remifentanil were used together. Data on phospho-38MAPK activation in remifenanil-induced hyperalgesia were contradictory and need further clarification.
a Department of Anesthesiology , General Hospital of Ningxia Medical University , Yinchuan City , China.
Liqin
L
Deng
b Department of Anesthesiology , Beijing Fengtai Hospital of Integrated Traditional and Western Medicine , Beijing , China.
Lihua
L
Zhang
c Graduate School of Ningxia Medical University , Yinchuan City , China.
Haiying
H
Zhao
c Graduate School of Ningxia Medical University , Yinchuan City , China.
Fengxiang
F
Song
c Graduate School of Ningxia Medical University , Yinchuan City , China.
Gang
G
Chen
c Graduate School of Ningxia Medical University , Yinchuan City , China.
Hanyue
H
Zhu
D000701:Analgesics, Opioid / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D006930:Hyperalgesia / Q000139:chemically induced* / Q000473:pathology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy; D010880:Piperidines / Q000009:adverse effects*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D010880:Piperidines; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D000077208:Remifentanil
Hyperalgesia; Remifentanil; Spinal dorsal horn; p38 mitogen-activated protein kinase