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Article: Propofol attenuates postoperative hyperalgesia via regulating spinal GluN2B-p38MAPK/EPAC1 pathway in an animal model of postoperative pain

TitlePropofol attenuates postoperative hyperalgesia via regulating spinal GluN2B-p38MAPK/EPAC1 pathway in an animal model of postoperative pain
Authors
Keywordsanalgesic activity
animal cell
animal experiment
animal model
drug mechanism
Issue Date2019
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1532-2149
Citation
European Journal of Pain, 2019, v. 23 n. 4, p. 812-822 How to Cite?
AbstractBackground: Total intravenous anesthesia with propofol has been shown to reduce postoperative pain in some clinical studies, but knowledge of its underlying analgesic mechanism remains limited. In this study, we compared the analgesic effects of propofol versus isoflurane in an animal model of postoperative pain and evaluated its underlying molecular mechanisms. Methods: Plantar incision was made in the hind paws of rats under general anesthesia with 2.5% of inhalational isoflurane (isoflurane group) or intravenous infusion of propofol (1.5 mg kg−1 min−1, propofol group). Mechanical allodynia was assessed by paw withdrawal threshold before and after incision. Spinal dorsal horns (L3–L5) were harvested 1 hr after incision to assess the level of phosphorylated GluN2B, p38MAPK, ERK, JNK, and EPAC using Western blot and immunofluorescence. Results: Mechanical allodynia induced by plantar incision peaked at 1 hr and lasted for 3 days after incision. It was significantly less in the propofol group compared with the isoflurane group in the first 2 hr following incision. The incision‐induced increases in phosphorylated GluN2B, p38MAPK, and EPAC1 were significantly reduced in the propofol group. The number of spinal dorsal neurons co‐expressed with EPAC1 and c‐Fos after the incision was significantly lower in the propofol group. Conclusion: Propofol reduced pain responses in an animal model of postoperative pain and suppressed the spinal GluN2B‐p38MAPK/EPAC1 signaling pathway. Since the p38MAPK/EPAC pathway plays a critical role in the development of postoperative hyperalgesia, our results provide evidence‐based behavioral, molecular, and cellular mechanisms for the analgesic effects of propofol when used for general anesthesia. Significance: These findings may provide a new mechanism for the postsurgical analgesic effect of propofol, which is particularly interesting during the subacute period after surgery as it is the critical period for the development of persistent postsurgical pain.
Persistent Identifierhttp://hdl.handle.net/10722/266500
ISSN
2023 Impact Factor: 3.5
2023 SCImago Journal Rankings: 1.132
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, SSC-
dc.contributor.authorSun, L-
dc.contributor.authorQIU, Q-
dc.contributor.authorGU, P-
dc.contributor.authorLi, Q-
dc.contributor.authorWang, XM-
dc.contributor.authorCheung, CW-
dc.date.accessioned2019-01-18T08:20:54Z-
dc.date.available2019-01-18T08:20:54Z-
dc.date.issued2019-
dc.identifier.citationEuropean Journal of Pain, 2019, v. 23 n. 4, p. 812-822-
dc.identifier.issn1090-3801-
dc.identifier.urihttp://hdl.handle.net/10722/266500-
dc.description.abstractBackground: Total intravenous anesthesia with propofol has been shown to reduce postoperative pain in some clinical studies, but knowledge of its underlying analgesic mechanism remains limited. In this study, we compared the analgesic effects of propofol versus isoflurane in an animal model of postoperative pain and evaluated its underlying molecular mechanisms. Methods: Plantar incision was made in the hind paws of rats under general anesthesia with 2.5% of inhalational isoflurane (isoflurane group) or intravenous infusion of propofol (1.5 mg kg−1 min−1, propofol group). Mechanical allodynia was assessed by paw withdrawal threshold before and after incision. Spinal dorsal horns (L3–L5) were harvested 1 hr after incision to assess the level of phosphorylated GluN2B, p38MAPK, ERK, JNK, and EPAC using Western blot and immunofluorescence. Results: Mechanical allodynia induced by plantar incision peaked at 1 hr and lasted for 3 days after incision. It was significantly less in the propofol group compared with the isoflurane group in the first 2 hr following incision. The incision‐induced increases in phosphorylated GluN2B, p38MAPK, and EPAC1 were significantly reduced in the propofol group. The number of spinal dorsal neurons co‐expressed with EPAC1 and c‐Fos after the incision was significantly lower in the propofol group. Conclusion: Propofol reduced pain responses in an animal model of postoperative pain and suppressed the spinal GluN2B‐p38MAPK/EPAC1 signaling pathway. Since the p38MAPK/EPAC pathway plays a critical role in the development of postoperative hyperalgesia, our results provide evidence‐based behavioral, molecular, and cellular mechanisms for the analgesic effects of propofol when used for general anesthesia. Significance: These findings may provide a new mechanism for the postsurgical analgesic effect of propofol, which is particularly interesting during the subacute period after surgery as it is the critical period for the development of persistent postsurgical pain.-
dc.languageeng-
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1532-2149-
dc.relation.ispartofEuropean Journal of Pain-
dc.rightsPostprint This is the peer reviewed version of the following article: [European Journal of Pain, 2019, v. 23 n. 4, p. 812-822], which has been published in final form at [http://dx.doi.org/10.1002/ejp.1349]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.-
dc.subjectanalgesic activity-
dc.subjectanimal cell-
dc.subjectanimal experiment-
dc.subjectanimal model-
dc.subjectdrug mechanism-
dc.titlePropofol attenuates postoperative hyperalgesia via regulating spinal GluN2B-p38MAPK/EPAC1 pathway in an animal model of postoperative pain-
dc.typeArticle-
dc.identifier.emailWong, SSC: wongstan@hku.hk-
dc.identifier.emailWang, XM: xmwang1@hku.hk-
dc.identifier.emailCheung, CW: cheucw@hku.hk-
dc.identifier.authorityWong, SSC=rp01789-
dc.identifier.authorityCheung, CW=rp00244-
dc.description.naturepostprint-
dc.identifier.doi10.1002/ejp.1349-
dc.identifier.pmid30570802-
dc.identifier.scopuseid_2-s2.0-85060968650-
dc.identifier.hkuros296641-
dc.identifier.hkuros319001-
dc.identifier.volume23-
dc.identifier.issue4-
dc.identifier.spage812-
dc.identifier.epage822-
dc.identifier.isiWOS:000461461500016-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl1090-3801-

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