***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: 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 Abstract Objective To evaluate the effect of the oral synthetic δ-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis . Design R and omised double blind placebo controlled crossovertrial . Setting Outpatient clinic , University Hospital of Aarhus , Denmark . Participants 24 patients aged between 23 and 55 years with multiple sclerosis and central pain . Intervention Orally administered dronabinol at a maximum doseof 10 mg daily or corresponding placebo for three weeks ( 15 - 21days ) , separated by a three week washout period . Main outcome measure Median spontaneous pain intensity ( numericalrating scale ) in the last week of treatment . Results Median spontaneous pain intensity was significantlylower during dronabinol treatment than during placebo treatment(4.0 ( 25th to 75th centiles 2.3 to 6.0 ) v 5.0 ( 4.0 to 6.4),P = 0.02 ) , and median pain relief score ( numerical rating scale)was higher ( 3.0 ( 0 to 6.7 ) v > 0 ( 0 to 2.3 ) , P = 0.035 ) . Thenumber needed to treat for 50 % pain relief was 3.5 ( 95 % confidenceinterval 1.9 to 24.8 ) . On the SF-36 quality of life scale , thetwo items bodily pain and mental health indicated benefits fromactive treatment compared with placebo . The number of patients with adverse events was higher during active treatment , especiallyin the first week of treatment . The functional ability of themultiple sclerosis patients did not change . Conclusions Dronabinol has a modest but clinical ly relevantanalgesic effect on central pain in patients with multiple sclerosis . Adverse events , including dizziness , were more frequent withdronabinol than with placebo during the first week of treatment Substance P is one of the neurotransmitters released by primary nociceptive neurons in the dorsal horn of the spinal cord and it binds postsynaptically to NK1‐receptors . This receptor is therefore an obvious target for analgesic drugs . The aim of this multicenter , r and omised , double‐blind , placebo‐controlled and parallel‐group study was to test if the non‐peptide NK1‐receptor antagonist TKA731 would relieve painful diabetic polyneuropathy . Eighty‐seven patients completed a treatment period of 2 weeks ' duration with TKA731  ( 150 mg daily ) or placebo preceded by one week for baseline observations . There was no significant difference between TKA731 and placebo in change in pain rating from baseline to study end neither for rating of total pain ( mean −13.4 mm vs. −11.6 mm , p = 0.664 ) nor for change in ratings of different pain symptoms ( touch‐ or pressure‐evoked pain , pain paroxysms , steady burning or deep aching pain ) ( p = 0.169‐0.834 ) Objective Oral amitriptyline , a tricyclic antidepressant , is effective for treating neuropathic pain . We conducted a double-blind , r and omized , placebo-controlled crossover study to evaluate the efficacy of topical 5 % amitriptyline and 5 % lidocaine in treating patients with neuropathic pain . Methods Thirty-five patients with postsurgical neuropathic pain , postherpetic neuralgia , or diabetic neuropathy with allodynia or hyperalgesia were assigned to receive 3 topical creams ( 5 % amitriptyline , 5 % lidocaine , or placebo ) in r and om sequence . The primary outcome measure was change in pain intensity ( baseline vs. posttreatment average pain ) using a 0 to 100 mm Visual Analog Scale . Secondary outcome measures included the McGill Pain Question naire , requirement for rescue medication , and patient satisfaction . Primary statistical comparisons were made with paired t tests or signed-rank tests . Results A reduction in pain intensity was observed with topical lidocaine ( P<0.05 ) . No significant change in pain intensity was found with topical amitriptyline or placebo . In pairwise comparison of treatments , topical lidocaine and placebo each reduced pain more than topical amitriptyline ( P<0.05 ) . Discussion This r and omized , placebo-controlled crossover study examining topical 5 % amitriptyline and 5 % lidocaine in the treatment of neuropathic pain showed that topical lidocaine reduced pain intensity but the clinical improvement is minimal and that topical 5 % amitriptyline was not effective Idiopathic , painful , small fiber predominant peripheral neuropathy is resistant to symptomatic treatment . Previous treatments have not been directed toward repairing the underlying deficit . Growth factors hold promise as agents to encourage axonal regrowth . In vitro , insulin-like growth factor-I ( IGF-I ) has been shown to prevent neuronal apoptosis , to increase axonal growth , and to support myelination . Using a double-blind , placebo-controlled design , 40 patients were r and omized to treatment with recombinant human IGF-I  ( 0.05 mg/kg twice daily by subcutaneous injection ) or placebo for 6 months . There were no significant adverse events and minor adverse events occurred equally in both groups . The primary outcome measure was change in score on an analog pain scale . Secondary endpoints included quantitative sensory testing , quantitative autonomic testing , neuropathy impairment score , nerve conduction studies , and neuropathy symptom and change score . There was no significant difference in the primary endpoint between the two groups . Analysis of secondary endpoints and a global impression of improvement by patients and physicians did not show consistent differences between the groups . IGF-I was safe , but did not improve symptoms in this 6-month trial & 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 OBJECTIVE To assess the efficacy of Sativex , a cannabis-based medicinal extract , as adjuvant treatment in painful diabetic peripheral neuropathy ( DPN ) . RESEARCH DESIGN AND METHODS In this r and omized controlled trial , 30 subjects with painful DPN received daily Sativex or placebo . The primary outcome measure was change in mean daily pain scores , and secondary outcome measures included quality -of-life assessment s. RESULTS There was significant improvement in pain scores in both groups , but mean change between groups was not significant . There were no significant differences in secondary outcome measures . Patients with depression had significantly greater baseline pain scores that improved regardless of intervention . CONCLUSIONS This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN . Depression was a major confounder and may have important implication s for future trials on painful DPN Distal sensory polyneuropathy ( DSP ) is the most frequent neurological complication of HIV infection . Neuropathic symptoms vary from mild paresthesias to severe pain that respond only partially to symptomatic treatment . Forty-five subjects with human immunodeficiency virus (HIV)-associated symptomatic DSP ( SDSP ) were enrolled in a r and omized , multicenter , 16-week placebo-controlled study of memantine , an N-methyl-d-aspartate ( NMDA ) uncompetitive antagonist . Although memantine was well tolerated , no trend toward clinical benefit was observed . Results were similar to those of other pilot studies of memantine for neuropathic pain unrelated to HIV , suggesting that memantine is ineffective for the symptomatic treatment of HIV-associated SDSP Abstract We sought to develop an enrichment crossover study design that would allow us to efficiently evaluate and compare promising c and i date neuropathic pain drugs . We evaluated the efficacy of gabapentin or tramadol vs. active placebo ( diphenhydramine ) in subjects with biopsy‐proven painful idiopathic small fiber neuropathy ( SFN ) who were self‐reported gabapentin responders . Eligible subjects entered two single blind run‐in phases . In the first phase ( Period A ) , subjects were treated with single blinded gabapentin at their pre study dose followed by a second run‐in phase ( Period B ) in which they were treated with diphenhydramine active placebo . Subjects with ⩾3 pain and a ⩾30 % increase in pain intensity in Period B compared to Period A were then r and omized to a double‐blind three period cross over trial of gabapentin at pre study dosage , tramadol 50 mg QID and diphenhydramine 50 mg qhs . Of the 59 subjects enrolled , 41 subjects were excluded : Twenty‐three had an insufficient rise in pain intensity in Period B ; eight had skin biopsies that did not confirm SFN . Eighteen subjects were r and omized into the double‐blind , crossover phase . There was a significant treatment effect of gabapentin vs. diphenhydramine ( p = 0.001 ) and tramadol vs. diphenhydramine ( p = 0.018 ) by the before‐bed daily pain score averaged over the final 7 days of each treatment period . We conclude that gabapentin and tramadol were effective in the treatment of painful SFN and that this experimental enrichment paradigm is attractive to screen potential neuropathic pain compounds for efficacy in proof‐of‐concept studies Objective : To evaluate the efficacy and tolerability of lamotrigine ( LTG ) for the treatment of pain in HIV-associated sensory neuropathies . Methods : In a r and omized , double-blind study , patients with HIV-associated distal sensory polyneuropathy ( DSP ) received LTG or placebo during a 7-week dose escalation phase followed by a 4-week maintenance phase . R and omization was stratified according to whether or not patients were currently using neurotoxic antiretroviral therapy ( ART ) . Results : The number of patients r and omized was 92 ( 62 LTG , 30 placebo ) in the stratum receiving neurotoxic ART and 135 ( 88 LTG , 47 placebo ) in the stratum not receiving neurotoxic ART . Mean change from baseline in Gracely Pain Scale score for average pain was not different between LTG and placebo at the end of the maintenance phase in either stratum , but the slope of the change in Gracely Pain Scale score for average pain reflected greater improvement with LTG than with placebo in the stratum receiving neurotoxic ART ( p = 0.004 ) , as did the mean change from baseline scores on the Visual Analogue Scale for Pain Intensity and the McGill Pain Assessment Scale and patient and clinician ratings of global impression of change in pain ( p ≤ 0.02 ) . The incidence of adverse events , including r 
    Output:
    
After controlling for potential confounders ( e.g. , subject characteristics , study design characteristics ) , the placebo response was found to be large and varied with the pain syndrome .
The type of treatment in the active arm also influenced the placebo response .
CONCLUSIONS Placebo response is influenced by the pain syndrome evaluated .