Premium
Paeoniflorin attenuates postoperative pain by suppressing Matrix Metalloproteinase‐9/2 in mice
Author(s) -
Fan Y.x.,
Hu L.,
Zhu S.h.,
Han Y.,
Liu W.t.,
Yang Y.j.,
Li Q.p.
Publication year - 2018
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.1116
Subject(s) - paeoniflorin , microglia , matrix metalloproteinase , medicine , allodynia , neuroinflammation , p38 mitogen activated protein kinases , pharmacology , mapk/erk pathway , western blot , nociception , anesthesia , chemistry , inflammation , kinase , immunology , hyperalgesia , receptor , biochemistry , high performance liquid chromatography , chromatography , gene
Background Recent studies have implicated that matrix metalloproteinase ( MMP )‐9 and MMP ‐2 play key roles in neuropathic pain due to their facilitation of inflammatory cytokine maturation and induction of neuroinflammation. However, the role of MMP ‐9/2 in postoperative pain is still unclear. We previously suggested that the natural compound paeoniflorin inhibited microglia activation induced by morphine treatment. In the present study, we demonstrated that paeoniflorin could alleviate postoperative pain via specific inhibition of matrix metalloproteinases ( MMP s). Methods Mice received a plantar incision surgery and their mechanical allodynia was assessed with von Frey filaments. The activity of MMP ‐9/2 was determined by gelatin zymography. Cell signalling was assayed by western blot and immunohistochemistry. Results The expression of MMP ‐9/2 was significantly increased in mice spinal cords with plantar incision surgery. Paeoniflorin remarkably suppressed the activity of MMP ‐9/2 and relieved plantar incision‐induced mechanical allodynia. Interestingly, the administration of paeoniflorin blocked the maturation of interleukin‐1β, which is a critical substrate of MMP s. Thereafter, paeoniflorin markedly suppressed microglia activation, inhibited the phosphorylation of p38 mitogen‐activated protein kinase ( MAPK ) and the expression of neuronal c‐Fos. Conclusion These results indicated that MMP ‐9/2 activation in spinal microglia plays a key role in incision‐induced mechanical allodynia in mice. Moreover, utilizing paeniflorin blockage of the microglia MMP ‐9/2 activity might represent a valuable alternative for treating postoperative pain. Significance Our results provided direct evidence for the first time that paeoniflorin can inhibit plantar incision‐induced microglia TLR4/MMP‐9/2/IL‐1β signalling pathway and suppress postoperative pain. Thus, regulation of microglia MMP‐9/2 may provide a new strategy for ameliorating postoperative pain.