Establishment Of Postsurgical Pain Evoked By Skin/muscle Incision And Retractionin Mouse And Assessment Of Its Characterization

Obejective:To verify the stability of skin/muscle incision and retraction model in mouse by ethology and to investigate the feasibility of establishing an animal model of chronic postsurgical pain in mouse.Furthermore,we assess effect of kinds of analgesics on this model and its characteristics.Methods:(1)Mouse were randomly assigned to 2 groups:skin/muscle incision and retraction(SMIR)group and skin/muscle incision without retraction(Sham)group,Paw withdrawal thresholds to mechanical stimuli and heat stimuli were recorded at dayl before surgery,day 1,day 3,day 7,day 10,day 14 and 18 after surgery.(2)Evaluating the analgesic effects of clonidine,dexmedetomidine and gabapentin on SMIR in mice:systemic injection clonidine(0.02mg/kg?0.1mg/kg?0.5mg/kg),dexmedetomidine(0.4ug/kg?2ug/kg?lOug/kg)and gabapentin(10mg/kg?20mg/kg?50mg/kg)on day 3 after surgery,assessing the effect on mechanical withdrawal thresholds.Evaluating the effects of clonidine,dexmedetomidine and gabapentin on the spontaneous pain by using a conditional place preference(CPP)behavioral paradigm:systemic injection clonidine(0.5mg/kg),dexmedetomidine(lOug/kg)and gabapentin(50mg/kg)on day 4 after surgery,observing whether they can arise CPP.Results:(1)SMIR-evoked mechanical hypersensitivity was observed by postoperative dayl(P<0.001),most prominent between postoperative days 1-10(P<0.001),persisted until at least postoperative day 14(P<0.05)and had dissipated by postoperative day 18.SMIR did not evoke significant heat hyperalgesia(P>0.05).(2)Systemic injection of clonidine,dexmedetomidine and gabapentin raised the PWTs in SMIR mice,and these effects were dose dependent.Systemic injection of 0.5mg/kg clonidine,lOug/kg dexmedetomidine alleviated spontaneous pain by chronic surgery pain in the CPP test,but 50mg/kg gabapentin did not alleviated spontaneous pain,there was no significant difference in preference changes to conditioning-box.ConclusionThese data suggests that skin/muscle incision and retraction model in mice evokes a persistent pain syndrome.Clonidine,dexmedetomidine and gabapentin can relieve mechanical hyperalgesia on dose-dependent.furthermore,0.5mg/kg clonidine and lOug/kg dexmedetomidine can alleviate spontaneous pain of SMIR,but 50mg/kg gabapentin cannot alleviate spontaneous pain of SMIR.