The Reserach Of Metformin In The Treatment Of Neuropathic Pain

Neuropathic pain(NP)is defined as pain caused by a lesion or disease of the somatosensory system.In view of the specific pathogenesis and refractory disease,NP has become the clinical treatment difficulty. Now gabapentin and tramadol are conventional drugs for the treatmen of NP,but only a quarter NP patients achieve the half of the pain relief.Researches have showed that metformin as a activator of adenosine monophosphate activated protein kinase(AMPK) may relieve symptoms of pain by inhibiting related signaling pathways. The clinical research on metformin for the treatment of NP is less.From the perspective of combination treatment,the study offer some research data by observing whether metformin can safely use in clinical treatment of NP.【Objective】1.To observe the therapeutical effect and anxiousdepressive disorder of metformin to different ages with NP patients during the therapeutic period.2.To assess the safety of the clinical application and possible mechanisms in the metformin treatment of NP by investigating the adverse reactions and changes of inflammatory cytokines level.【Methods】1.168 patients with NP who came to the Affiliated Hospital of Jiangsu University and were in accordance with the inclusive and exclusive criteria from Sep 2013 to Jul 2015 were included. According to randomized block design,these patients with NP were divided into three age blocks:A(n=48,18~40 years old) block 、B(n=54, 41~60 years old)block 、C(n=66, above 60 years old)block.2. each block was divided into two groups.GroupⅠwere oral administration of gabapentin capsules 300 mg Tid and tramadol hydrochloride sustained-release tablets 100 mg Bid according to our hospital routine, while the groupⅡwas metformin hydrochloride sustained-release tablets 500 mg Bid additionally.The courses of treatment were 6 months between two groups.3. VAS scores 、 anxiousdepressive disorder scores 、 serum high-sensitivity C-reactive protein(HS-CRP) level、serum tumor necrosis factor-α(TNF-α) level 、hepatorenal function indexes and adverse reactions of patients during pretreatment(T0) 、three months(T1) and six months(T2) after treatment in the two groups were recorded and analyzed.【Results】1. The VAS scores of each block had no significant difference between two groups at T0 point(P>0.05);The VAS scores were decreased significantly in patients with the younger age after treatment at T1 and T2 points(P<0.05);Compared to the groupⅠ,the VAS scores of Ⅱ were decreased obviously and the downtrend was significant with the extension of treatment(P<0.05). The interaction effect of therapeutic method and time between groupsⅠand Ⅱhad statistical significance(P<0.05);The inter-group comparsion of VAS scores had a significant difference between two groups( P < 0.05);There were a significant differences in time comparison of VAS scores(P<0.05).2. GroupsⅠand Ⅱhad no significant difference on the overall effective rate of PAR at T2 point(P>0.05),but the total significant efficiency of groupⅡwas higher thanⅠ(P<0.05).3. The anxiousdepressive disorder scores were lower in patients with the younger age at T0 point(P<0.05);The scores of groups with the same age were decreased after treatment(P<0.05). There were a significant differences in time comparsion of anxiousdepressive disorder scores between groupsⅠand Ⅱ(P<0.05).4.The VAS scores were positively correlated with the anxiousdepressive disorder scores at three time points between groupsⅠand Ⅱ(P<0.05).5.The serum level changes of high-sensitivity C-reactive protein(HS-CRP) was positive correlation with age at T0 point between groupsⅠand Ⅱ(P<0.05); Compared to T0,the level of HS-CRP and tumor necrosis factor-α(TNF-α) were lower at T2(P<0.05);Compared with the groupⅠ,these changes of groupⅡwere decreased obviously in same age groups(P<0.05).6. The VAS scores were positively correlated with HS-CRP level at T0 and T2 points between groupsⅠand Ⅱ(P<0.05).7.There were no significant changes of aspartate transaminase、alanine aminotransferase、blood urea nitrogen、creatinine、vitamine B12、fasting blood glucose in the groupⅡat three time points(P>0.05).8.There was no significant difference for the incidences of gastrointestinal discomfort、dizziness、somnolence and ataxia symptoms in groupsⅠandⅡ after treatment(P>0.05).【Conclusion】1.Compared with gabapentin and tramadol groups,metformin combined those two drugs had been found more analgesic effect and no increased adverse effects.2.There were positive correlation among pain degree, anxiousdepressive disorder degree and inflammatory cytokines level. 3.The treatment effect was influenced by age – young tendency,the better therapeutic effect.