***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: Abstract In a double blind , placebo controlled trial of 40 volunteers , the burning discomfort associated with application of capsaicin cream ( 0.025 % ) was compared to placebo , GTN cream ( 1.33 % ) and to the combination of capsaicin cream ( 0.025 % ) plus GTN cream 1.33 % . Median VAS for burning pain were 0 for the placebo , GTN and GTN+capsaicin groups and 3 for the capsaicin group after single application of each cream at daily intervals . This study demonstrates that after single application the addition of GTN to capsaicin significantly reduces the burning discomfort associated with application of capsaicin alone Experimental studies have indicated that N-methyl-D-aspartate ( NMDA ) receptor antagonists may be effective analgesics in a wide variety of chronic pain states . The mechanism is presumed to be related to decreased firing of dorsal horn neurons after constant repeated C-fiber stimulation . Dextromethorphan ( DM ) , a potent NMDA antagonist with a good safety profile , may be a promising agent for the treatment of persistent pain . An open-label r and omized trial was design ed to examine the effects of combining DM with NSAIDs , dextropropoxyphene , or morphine in cancer patients with pain . Patients who required a change in the step of the World Health Organization 's ( WHO ) analgesic ladder because of a pain level of 4 or more on a numerical pain scale were r and omly allocated to receive DM 30 mg three times a day ( 30 patients ) or conventional treatment ( 30 patients ) . There were 20 patients r and omized for each step of the analgesic ladder . Pain mechanisms , pain intensity ( numerical 0 - 10 scale ) , symptoms more frequently present in advanced cancer patients or associated with  opioid therapy  ( grade d on a 0 - 3 scale -- not at all , slight , a lot , awful ) , opioid escalation index , days on opioid treatment , and adverse effects were recorded . After 2 days 75 % , 80 % , and 100 % of patients treated with DM in steps 1 , 2 , and 3 , respectively , required conventional treatment , because adequate pain relief had not been achieved ( pain scale > 4 ) . Failure of this treatment was equally observed in neuropathic pain or nociceptive pain syndromes . Four patients treated with DM who did not require the conventional treatment immediately did require this change after some days , due to poor pain control . A highly significant reduction in pain was observed in patients directly treated with the conventional treatment in all the three steps of the analgesic ladder . No significant analgesic effects could be found when DM at this dose was combined with NSAIDs , dextropropoxyphene , or morphine Aims and Background Amitriptyline is the most common analgesic adjuvant used in cancer patients with neuropathic pain , even though no specific studies have demonstrated a benefit . A r and omized placebo-controlled , double-blind crossover study was design ed to evidence the effects of amitriptyline in patients with neuropathic cancer pain . Methods Sixteen advanced cancer patients with neuropathic pain on systemic morphine therapy , no longer receiving oncologic treatment , presenting moderate pain ( about 4 or more , but less than 7 , on a numerical scale of 0 - 10 ) in the last week , and given a stable morphine dose in the last 2 days were admitted to the study . During the first week of study , patients were administered 25 mg of amitriptyline or equivalent drops of placebo at night for 3 days and 50 mg for the following 4 days . Doses for patients aged more than 65 years were 15 mg ( first 3 days ) and 30 mg ( 3 days after ) . After a week , a crossover took place for the second week , with the other treatment at an inverse sequence . Opioid consumption , pain intensity , symptoms and adverse effects , mood , sleep , patient 's preference , quality of life before starting the study , the first week after and the second week after were recorded . Results No significant benefits in analgesia were found in the global pain intensity of the previous week of treatment , the least pain intensity or the pain evaluated just after a week of treatment , at the moment of the visit , when amitriptyline was compared with placebo . A significant difference was evidence d for the worst pain ( P < 0.035 ) . No differences in opioid doses during the period of study were found . Drowsiness , confusion and dry mouth were significantly more intense with amitriptyline than with placebo ( P < 0.036 , 0.003 , and 0.034 , respectively ) . There were no substantial differences between the two treatments in Spitzer 's quality of life score and for each item . No differences in patients ' preference for the two treatment periods were found . The analgesic effects of amitriptyline were slight and associated with adverse effects . Conclusions In light of the results obtained in the study , the extensive use of the drug for cancer pain should be question ed Neuropathic cancer pain represents a major challenge . Treatment often requires adjuvant analgesics , including gabapentin , to complement the effects of opioids . This study aim ed to compare the effectiveness and safety of gabapentin combined with an opioid versus opioid monotherapy for the management of neuropathic cancer pain . Seventy-five cancer patients who were receiving opioid therapy and reported sufficient pain relief of nociceptive , but not neuropathic , pain were enrolled . Sixty-three patients completed the study . Patients were r and omized to one of the following treatment protocol s : 1 ) gabapentin adjuvant to ongoing opioid treatment titrated according to pain response while opioid dose was kept constant ( group GO ) , and 2 ) continuation of opioid monotherapy according to the World Health Organization treatment ladder approach ( group OO ) . Changes in pain intensity , allodynia , and analgesic drug consumption were evaluated at Day 4 and Day 13 . Side effects were also recorded . Both treatments result ed in a significant reduction of pain intensity at Day 4 and Day 13 compared to baseline . However , mean pain intensity for burning and shooting pain was significantly higher in the OO group compared to the GO group at both the fourth ( P=0.0001 ) and 13th ( P=0.0001 ) days of the study . An earlier significant decrease ( at Day 4 , P=0.002 ) was observed for allodynia in the GO group compared to the OO group . The rate of side effects in the GO group was significantly lower than that in the OO group ( P=0.015 ) . These data suggest that gabapentin added to an opioid provides better relief of neuropathic pain in cancer patients than opioid monotherapy ; this combination of gabapentin and an opioid may represent a potential first-line regimen for the management of pain in these patients & NA ; Topical aspirin/diethyl ether ( ADE ) mixture was used to treat 45 consecutive patients with acute herpetic neuralgia ( AHN ) ( n = 28 ) and with post‐herpetic neuralgia ( PHN ) ( n = 17 ) in an open‐label study . Good‐to‐excellent results were achieved by 93 % of AHN patients and by 65 % of PHN patients . Earlier treatment yielded better results for the AHN but not the PHN group . The topical treatment seemed to accelerate the healing of acute herpetic skin lesions and possibly modulate the severity of the herpetic infection . Furthermore , a striking reduction in the percentage of AHN patients developing PHN was observed in the treated group , as compared with the disease natural history reported in the literature ( 4 vs. 50–70 % ) . Treatment tolerance was excellent with no adverse effect observed . In addition to the open trial , a pilot double‐blind crossover placebo‐controlled study ( n = 11 ) compared the analgesic efficacy  of ADE with two other NSAID ( indomethacin and diclofenac ) drug/ether mixtures . Aspirin ( but not indomethacin and diclofenac ) was significantly superior to placebo as regards pain relief ( P < 0.05 ) Abstract  Variability  in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Background We have recently reported successful treatment of patients with chronic pain syndromes  using human pooled intravenous immunoglobulin ( IVIG ) in a prospect i ve , open-label cohort study . A r and omised , placebo controlled , double blinded study is needed to confirm these results . We chose to study patients with carbamazepine resistant primary Trigeminal Neuralgia ( rpTN ) , as these had responded particularly well to IVIG.A protocol involving the use of IVIG in rpTN is complex for three reasons : 1 . The effect of IVIG does not follow simple dose-response rules ; 2 . The response pattern of patients to IVIG was variable and ranged between no effect at all and pain free remission between two weeks and > 1 year ; 3 . TN is characterized by extremely severe pain , for which operative intervention is ( if temporarily ) helpful in most patients . Design A placebo controlled , parallel , add-on model was developed and the primary outcome variable defined as the length of time during which patients remain in the study . Study groups are compared using Kaplan-Maier survival analysis . Patients record their response to treatment ( " severe , moderate , slight , no pain " ) . The study coordinator monitors pain diaries . Severe or moderate pain of three days duration will result in termination of the study for that patient . Conclusions This study design utilizes a method of survival analysis and is novel in chronic pain research . It allows for both early departure from the study and voluntary crossover upon non-response . It may be applicable to the analysis of IVIG efficacy in other chronic pain syndromes & NA ; Levodopa has been used to treat some painful conditions and found to be effective in neuropathic pain due to herpes zoster in a double‐blind study . From our anecdotal observations about the efficacy of levodopa on diabetic neuropathic pain , we design ed a double‐blind placebo‐controlled study to test levodopa in painful diabetic neuropathy . Twenty‐five out‐ patients with painful symmetrical diabetic polyneuropathy were admitted to the study . Fourteen patients were given 100 mg levodopa plus 25 mg benserazide to be taken three times per day for 28 days . Eleven patients were given identical placebo capsules . A blinded neurologist evaluated the patients clinical ly and performed Visual Analogue Scale ( VAS ) measurement every week from day 0 to day 28 . The results seemed promising and levodopa may be a choice for the control of pain in neuropathy for which we do not have many alternative treatments This observational study examined the outcome of two different therapeutic strategies in the treatment of chronic neuropathic pain by including pregabalin ( PGB ) as mono- or add-on therapy in one of two treatment options . Patients with a pain score of ≥4 , refractory to usual care for neuropathic pain for at least 6 months , were allocated consecutively to one of two treatment strategies according to the decision of the physician : complete switch to a flexible-dosage , monotherapeutic or add-on therapy with pregabalin ( PGB group ) , or change established doses and combinations of pre-existing mono- or combination therapy without pregabalin ( non-PGB group ) . After 4 weeks ( primary endpoint ) a significant improvement in pain reduction was documented in both intention-to treat ( ITT ) analysis ( PGB group , n = 85 : mean pain score reduction of 3.53 , SD 2.03 , p < 0.001 ; non-PGB group , n = 102 ; mean pain score reduction of 2.83 , SD 2.23 , p < 0.001 ) and per- protocol ( PP ) analysis ( PGB group , n = 79 : mean pain score reduction 3.53 vs. 2.83 , p < 0.05 ; non-PGB group , n = 81 ; 3.5 vs. 2.9 , p < 0.05 ) compared to baseline . Comparison of the 
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However , this combination also produced significantly more frequent side effect-related trial dropouts compared to gabapentin alone .
AUTHORS ' CONCLUSIONS Multiple , good- quality studies demonstrate superior efficacy of two-drug combinations .
However , the number of available studies for any one specific combination , as well as other study factors ( e.g. limited trial size and duration ) , preclude the recommendation of any one specific drug combination for neuropathic pain .