***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: A double blind placebo controlled trial was performed to evaluate the effects of the aldose reductase inhibitor , ponalrestat , on  symptomatic diabetic neuropathy .  After a 4-week placebo run-in phase , 60 patients were 2:1 r and omized to receive either 600 mg ponalrestat or placebo once daily over 12 months . Forty-six patients , 30 of whom were treated with ponalrestat and 16 with placebo , completed the study .  Motor and sensory nerve conduction , thermal and vibration sensation thresholds , heart rate variation at rest , E/I ratio , pupillary dilation velocity and pupillary reflex latency were determined at baseline and after 6 and 12 months . Neuropathic symptom scores were assessed every 3 months . Among the fifteen nerve function parameters studied , only trends in favour of ponalrestat were noted for heart rate variation and E/I ratio after 6 months ( P = 0.06 ) , but no significant differences between the groups could be demonstrated during the study . No adverse reactions were observed . It is concluded that one-year treatment with ponalrestat has no beneficial effects on symptoms or electrophysiological parameters in diabetic neuropathy One hundred and ninety patients with symptomatic diabetic peripheral neuropathy took part in a double blind multicentre trial of either placebo or tolrestat 200 mg once daily for 6 months . Painful and paraesthetic symptoms , vibration sensory threshold , and nerve conduction velocity ( NCV ) were assessed as efficacy end-points during the trial . There was an equally marked improvement of painful symptoms during the trial in the tolrestat and placebo groups . A difference in the improvement of paraesthetic symptoms was found however in favour of the placebo group at 24 weeks ( p less than 0.02 ) . The deterioration in mean vibration threshold of the tolrestat group was less than placebo at 24 weeks at all 3 sites measured , and reached significance at the carpal site ( p less than 0.05 ) . Significant improvements in median motor NCV and in the mean NCV of the four motor nerves were also seen in tolrestat treated patients at 24 weeks compared to placebo ( p less than 0.05 ) . In addition , significant changes in favour of tolrestat were seen when the number of motor nerves per patient with NCV increased during the trial was analysed ( p less than 0.001 ) . Concordance analysis of patients with increased mean motor NCV and improvement in painful symptoms demonstrated a positive effect for tolrestat compared to placebo ( p less than 0.02 ) . Mild reversible elevations of hepatic transaminases were seen in a few patients treated with tolrestat , with no other significant adverse effects . Tolrestat may therefore be helpful in diabetic peripheral neuropathy , where there is little opportunity for therapeutic intervention apart from effort to achieve normoglycaemic control Background There are few repeated dose-controlled trials of N-methyl-d-aspartate glutamate receptor antagonists in patients with neuropathic pain . The authors sought to evaluate two low-affinity N-methyl-d-aspartate antagonists using a novel two-stage design . Methods The authors studied patients with painful diabetic neuropathy ( DN ) and postherpetic neuralgia ( PHN ) in two crossover trials : ( 1 ) efficacy trial ( dextromethorphan vs. memantine vs. active placebo [ lorazepam ] ) and ( 2 ) dose – response trial of the preferred active drug in responders from the first study ( 0%vs . 25%vs . 50%vs . 100 % of each patient 's maximally tolerated dose ) . Pain intensity was measured on a 20-point scale . Results Nineteen of 23 DN patients and 17 of 21 PHN patients completed the efficacy trial .  Median doses for DN and PHN were 400 and 400 mg/day dextromethorphan , 55 and 35 mg/day memantine , and 1.8 and 1.2 mg/day lorazepam . In the efficacy trial , among patients with DN , dextromethorphan  reduced pain intensity by a mean of 33 % from baseline , memantine  reduced pain intensity by a mean of 17 % , and lorazepam  reduced pain intensity by a mean of 16 % ; the proportions of subjects achieving greater than moderate pain relief were 68 % with dextromethorphan , 47 % with memantine , and 37 % with lorazepam .  Mean reductions in pain intensity in patients with PHN were 6 % with dextromethorphan , 2 % with memantine , and 0 % with lorazepam . No comparison with placebo reached statistical significance in the efficacy trial . In the 10 DN subjects who responded to dextromethorphan , there was a significant dose – response effect on pain intensity ( P = 0.035 ) , with the highest dose significantly better than that of lorazepam ( P = 0.03 ) . Conclusions Dextromethorphan is effective in a dose-related fashion in selected patients with DN . This was not true of PHN , suggesting a difference in pain mechanisms . Selective approaches to pain-relevant N-methyl-d-aspartate receptors are warranted Background Peripheral diabetic neuropathy affects between 20 % and 45 % of patients with diabetes . Objective To ascertain the effect of lacosamide on pain associated with peripheral diabetic neuropathy . Methods One hundred nineteen patients with a 1 to 5-year history of pain attributed to diabetic neuropathy and a score of ≥4 on the Likert pain scale entered the multicenter , r and omized , double-blind , placebo-controlled trial . Lacosamide ( N=60 ) titrated from 100 to 400 mg/d or maximum tolerated dose and placebo ( N=59 ) were the trial interventions . Primary efficacy criterion was change in pain score on the 11-point Likert pain scale . Secondary assessment s included Short-Form McGill Pain and Short-Form-36 Quality of Life Question naires , sleep/activity interference , pain intensity , Patient and Clinical Global Impression of Change , and Profile of Mood .  Patients receiving at least 1 dose of medication underwent safety evaluation . Results Ninety-four patients ( lacosamide 46 ; placebo 48 ) completed the trial . Lacosamide had significantly ( P=0.039 ) better pain relief  versus placebo ( primary outcome ) . Improvements were also seen in secondary outcome measures . Adverse events occurred in 52 lacosamide and 44 placebo patients . Common adverse events , occurring in ≥5 % of patients , were headache  ( lacosamide 18 % , placebo 22 % ) , dizziness  ( lacosamide 15 % , placebo 8 % ) , and nausea  ( lacosamide 12 % , placebo 7 % ) . Five lacosamide and 3 placebo patients withdrew for adverse events . Discussion Lacosamide seems to attenuate pain in diabetic neuropathy in doses up to 400 mg/d and improves quality of life issues Abstract Aims / Introduction : Duloxetine has been suggested to exert analgesic effects by activating the descending inhibitory system through inhibition of serotonin ( 5‐HT ) and noradrenaline ( NA ) reuptake . This r and omized controlled trial investigated the efficacy and safety of duloxetine in Japanese patients with diabetic neuropathic pain ( DNP ) . Material s and Methods : Duloxetine 40 or 60 mg/day or placebo was given orally once daily for 12 weeks . The primary efficacy measure was weekly mean 24‐h average pain severity score on the 11‐point Numerical Rating Scale . Results : At 12 weeks vs baseline , the 24‐h average pain score ( adjusted mean ± SE ) was significantly improved in the combined duloxetine ( −2.47 ± 0.18 ) and duloxetine 40 mg ( −2.41 ± 0.21 ) and 60 mg groups ( −2.53 ± 0.21 ) as compared with the placebo group ( −1.61 ± 0.18 ) . Duloxetine also exerted significant improvements over the placebo in nearly all secondary outcome measures including 24‐h worst pain , night pain , Brief Pain Inventory ( BPI ) pain scores , Patient ’s Global Impression of Improvement ( PGI‐I ) and health outcome measures , namely , various BPI interference scores . The incidence of adverse events ( AE ) was higher in the duloxetine groups than in the placebo group ( duloxetine overall , 84.8 % ; duloxetine 40 mg , 84.7 % ; duloxetine 60 mg , 84.9 % ; placebo , 73.7 % ) . Most AE were mild or moderate in severity , and resolved or relieved . There were no clinical ly significant safety concerns . Conclusions : Duloxetine 40 or 60 mg/day showed superiority over the placebo at reducing pain scores in patients with DNP . Duloxetine is safe , efficacious and clinical ly useful in the management of DNP . This trial was registered with Clinical Trials.gov ( no. NCT‐00552175 ) . ( J Diabetes Invest , doi : 10.1111/j.2040‐1124.2010.00073.x , 2010 OBJECTIVE We conducted an 8-wk controlled study with topical 0.075 % capsaicin in subjects with chronic severe painful diabetic neuropathy who were unresponsive or intolerant to conventional therapy .  Capsaicin is an alkaloid found in capsicum peppers and produces desensitization to noxious thermal , chemical , and mechanical stimuli when applied topically . RESEARCH DESIGN AND METHODS In 22 r and omly assigned subjects , either capsaicin or vehicle cream was applied to painful areas 4 times/day . Pain measurements were recorded at baseline and at 2-wk intervals for 8 wk . RESULTS Capsaicin treatment was more beneficial than vehicle treatment in the overall clinical improvement of pain status , as measured by physician 's global evaluation ( P = 0.038 ) and by a categorical pain severity scale ( P = 0.057 ) . Decrease in mean pain intensity by a visual analogue scale was 16 % in capsaicin-treated and 4.1 % in vehicle-treated subjects . Mean pain relief on visual analogue scale was 44.6 and 23.2 % , respectively . In a follow-up open-label study , approximately 50 % of subjects reported improved pain control or were cured , and 25 % each were unchanged or worse . A burning sensation at the application site was noted by some subjects but both its magnitude and duration decreased with time . CONCLUSIONS Results from this preliminary study suggest that topical 0.075 % capsaicin may be of value in subjects with diabetic neuropathy and intractable pain AIMS To compare the efficacy and safety of lamotrigine and amitriptyline in controlling chronic painful peripheral neuropathy in diabetic patients . METHODS A r and omized , double-blind , crossover , active-control , clinical trial with variable dose titration was carried out ( n = 53 ) . Amitriptyline orally , at doses of 10 , 25 and 50 mg at night-time , each dose for 2 weeks , and lamotrigine orally , at doses of 25 , 50 and 100 mg twice daily , each dose for 2 weeks , by optional titration were used . There was a placebo washout period for 2 weeks between the two drugs . Assessment for pain relief , overall improvement and adverse events were carried out . RESULTS Good , moderate and mild pain relief were noted in 19 ( 41 % ) , six ( 13 % ) and seven ( 15 % ) patients on lamotrigine and 13 ( 28 % ) , five ( 11 % ) and 15 ( 33 % ) patients on amitriptyline , respectively , by patient 's global assessment of efficacy and safety . Patient and physicians global assessment , McGill pain question naire and Likert pain scale showed no significant difference between the treatments , although improvement with both treatments was seen from 2 weeks . Of the 44 adverse events reported , 33 ( 75 % ) were with amitriptyline , sedation being the commonest [ in 19 ( 43 % ) patients ] . Lamotrigine caused adverse events in 11 ( 25 % ) , of which rash in three ( 7 % ) and elevations of creatinine in four ( 9 % ) were the most common . The preferred lamotrigine dose was 25 mg twice daily . CONCLUSIONS As there are few differences between the two treatments in efficacy , lamotrigine 25 mg twice daily might be the first choice as it is associated with fewer adverse effects in our population An 8-week double-blind , multicenter , parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet . Two hundred thirty-five patients were r and omized to treatment with either capsaicin cream or amitriptyline capsules . Capsaicin-treated patients received inactive capsules , and amitriptyline-treated patients applied vehicle cream . A visual analogue scale of pain intensity and measurements of interference by pain with functional 
    Output:
    
Network meta- analysis showed that SNRIs ( SMD , -1.36 [ CrI , -1.77 to -0.95 ] ) , topical capsaicin ( SMD , -0.91 [ CrI , -1.18 to -0.08 ] ) , TCAs ( SMD , -0.78 [ CrI , -1.24 to -0.33 ] ) , and anticonvulsants ( SMD , -0.67 [ CrI , -0.97 to -0.37 ] ) were better than placebo  for short-term pain control .
Several medications may be effective for short-term management of painful diabetic neuropathy , although their comparative effectiveness is unclear .