The Experimental Study On Analgesic Effects Of Pentoxifylline In The Rat Model Of Acute Pain

Objective:To investigate the effects of the single and the continuous pentoxifylline(PTX)injection of prior intraperitoneal administration applied on the plantar incision-induced postoperative hyperalgesia in rats.Methods:The postoperative pain rat model with plantar incision were used for this experiment.All sixty adult male Sprague-Dawley rats weighting range 180-250g were randomly divided into two groups:single-dose group(group Ⅰ)and the continuous treatment group(group Ⅱ).Then the group Ⅰ was divided into 5 subgroups(n=6):control group(group C)was given normal saline(NS),PTX treatment groups(group PTX1-4)were given 12.5,25,50 or 100mg/kg PTX by single time intraperitoneal administration.Meanwhile Group Ⅱ was divided into 5 subgroups(n=6):control group(group C)was given NS,pentoxifylline treatment groups(group PTX1-4)were administered PTX(12.5,25,50 or 100 mg/kg intraperitoneally)systemically daily.In the preoperative 30 minute,all subgroups of the group Ⅰ were given different doses of PTX intraperitoneally and the corresponding volume of NS individualy,and measured at each time point of the mechanical withdrawal threshold(MWT),thermal withdrawal latency and withdrawal duration at pre-incision(T0),then 1,3 and 5 hour after sugery(T1-3).From 30 minutes before the operation to day 1-7 post-operation,all subgroups of the group Ⅱ were systermically daily intraperitoneally administrated different doses of PTX and the corresponding volume of NS,and measured at each time point of the mechanical withdrawal threshold(MWT),thermal withdrawal latency and withdrawal duration at pre-incision(T0),then 1,2,3,5 and 7 days after surgery(T1-6).Anlimals were sacrificed after the tests of behavior in group Ⅱ,and then the spinal cord tissue samples of L4-6 in group C and PTX4 were analysised by using immunofluorescence technic and the expression or co-expression of phosphorylation of p38(p-p38),OX-42(microglia maker)and p-p38 co-clocalized with OX-42 positive cells(p-p38/OX-42)in L4-6 spinal dorsal horns were observed simultaneously.Results:①Comparison in the groups:In group I,MWT was higher at T,in group PTX3,4 than at T2(P<0.05 or P<0.01).Compared with T3,in group PTX3,4,WMT was increased at T1-2,and thermal withdrawal latency threshold was increased too,following thermal withdrawal duration reduced at T1(P<0.05 or P<0.01).In group Ⅰ,the number of the p-p38 positive cells at T1-4,the OX-42 at T4-5 and the p-p38/OX-42 at T2-5 in group C were significantly increased(P<0.01);and the number of the p-p38 positive cells at T2,the OX-42 and p-p38/OX-42 at T4 in group C reached the peak(compared with the group at each time point,P<0.01).②Comparison between groups:In group I,compared with group C,WMT was significantly raised at T1-2 in group PTX3,4.Furthermore,thermal threshold latency threshold was upregulated and thermal withdrawal duration was downregulated at T1 in group PTX3 and at T1-2 in group PTX4(P<0.05 or P<0.01).In group II,compared with group C,WMT was significantly increased at T1-4 in group PTX3,4.Thermal threshold latency threshold was upregulated at T,in group PTX3 and at T1-4 in group PTX4.Thermal withdrawal duration was negative regulator at T1-2 in group PTX3 and at T1-3 in group PTX4 in addition.The number of the p-p38 positive cells at T1-4,the OX-42 at T4-5 and the p-p38/OX-42 at T2-5 in PTX4 were reduced(P<0.05 or P<0.01).There data shown none significant difference between group PTX1,2 with group C,in group I and II(P>0.05).Conclusion:A significant increase in number of p-p38 and microglia(assessed by OX-42)immunoreactive cells were observed in the ipsilateral L4-5 spinal dorsal horn after the incision.Our results proved that they may play an important role in incision-induced mechanical allodynia and heat hyperalgesia in rats.Single and continuous intraperitoneal injections of PTX can prevent plantar incision-induced mechanical allodynia,but it only attenuated thermal hyperalgesia at an the very beginning.This analgesic effect of PTX may be associated with inhibition of p-p38 in microglia activation,meanwhile all the analgesic effects of pentoxifylline showed a dose-dependence.