***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: Background : Pain following spinal cord injury ( SCI ) is a therapeutic challenge . Only a few treatments have been assessed in r and omized , controlled trials . The primary objective of the present study was to examine the analgesic effect of ketamine and lidocaine in a group of patients with neuropathic pain below the level of spinal cord injury . We also wanted to assess sensory abnormalities to see if this could help us to identify responders and if treatments result ed in changes of sensibility Background Several lines of evidence suggest that neuropathic pain ( including Complex Regional Pain Syndrome [ CRPS ] I and CRPS II ) is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons . This study sought to characterize the effects of intravenous lidocaine ( a sodium channel blocker ) on acute sensory thresholds within the painful area and the size of the painful area in patients suffering from CRPS I and II . Methods This study used a r and omized , double-blind , placebo-controlled design in 16 subjects suffering from CRPS I and II with a prominent allodynia . Each subject received an intravenous infusion of lidocaine and diphenhydramine separated by 1 week . A computer-controlled infusion pump targeted stair-step increases in plasma levels of lidocaine of 1 , 2 , and 3 & mgr;g/ml . At baseline and at each plasma level , spontaneous and evoked pain scores and neurosensory testing within the painful area were measured . The neurosensory testing consisted of thermal thresholds , tactile thresholds and the area of allodynia to punctate , and stroking and thermal stimuli . Results Intravenous lidocaine and diphenhydramine had no significant effect on the cool , warm , or cold pain thresholds . However , lidocaine caused a significant elevation of the hot pain thresholds in the painful area . Intravenous lidocaine caused a significantly decreased response to stroking and cool stimuli in the allodynic area . There was also a significant decrease in pain scores to cool stimuli at all plasma levels and the spontaneous pain at the highest plasma level . Conclusions This study demonstrates that intravenous lidocaine affects pain in response to cool stimuli more than mechanical pain in subjects with neuropathic pain . There is a lesser effect on spontaneous pain and pain induced by stroking stimuli and no effect on the pain induced by punctate stimuli & NA ; In a double‐blind controlled design , 7 patients with painful diabetic neuropathy received lidocaine 5 mg/kg or saline intravenously over a period of 30 min . Thermal sensibility quantified by thermotest was not affected by lidocaine . In 3 of the patients nociceptive flexion reflex thresholds could be determined . The threshold was increased by lidocaine and returned to pre‐infusion level within 10 days . Lidocaine also increased the threshold in 4 healthy subjects , but did not affect the Hoffmann reflex . These results suggest that lidocaine exerts its pain‐relieving effect on the spinal level in diabetic neuropathy In a few uncontrolled studies intravenous lidocaine has been used in the treatment of  chronic pain .  In a controlled study we used intravenous lidocaine in 18 patients with severe chronic pain states due to various but mainly neurological diseases . After the infusion of lidocaine 14 patients ( 78 % ) had significant pain relief ranging from 2 hours to 25 days . There was no significant effect of placebo infusion with isotonic saline . The mechanism of the pain relieving ability of intravenous lidocaine is unknown Background and Objectives Mexiletine is a sodium channel blocker that has been used for the treatment of a variety of neuropathic pain syndromes . A recent double-blinded placebo-controlled study concluded that it was ineffective in the treatment of allodynia associated with neuropathic pain . However , this study failed to achieve adequate plasma levels of mexiletine . This was a study in healthy volunteers that sought to push the drug to dose-limiting side effects and then evaluate the effects on human experimental pain . Methods Twelve healthy volunteers were studied using a r and omized , double-blind , placebo-controlled crossover study . The subjects were titrated to a maximum dose of 1,350 mg/d or dose-limiting side effects , whichever occurred first . At baseline and day 10 and 17 , neurosensory testing , train-of-three thermal pulses , and side-effect measurements were performed and on day 17 , intradermal capsaicin was injected on the volar aspect of the forearm and the pain and secondary hyperalgesia to von Frey hair , stroking , and thermal stimuli were measured . Results Peak plasma levels occurred on day 10 and were 0.36 ± 0.21 μg/mL. All subjects experienced dose-limiting side effects . The mean maximum tolerable daily dose achieved was 859 mg ( range , 300 to 1,350 mg ) . The side effects reported by the subjects included nausea , lightheadedness , muscle twitching and weakness , blurred vision , headache , tremors , difficulty concentrating , dysphoria , sedation , pruritis , and rash . These side effects occurred at an average daily dose of 993 mg ( range , 600 to 1,350 mg ) . Compared with placebo , mexiletine had no significant effects on any of the neurosensory thresholds and pain scores after intradermal capsaicin . There was a significant reduction in the area of secondary hyperalgesia to von Frey hair stimulation only . There was a significant correlation between plasma mexiletine level and flare response . Conclusions Mexiletine has minimal effects on human experimental pain . It is severely limited by side effects and tolerable doses seem to be void of effects on normal neurosensation and facilitated pain induced by capsaicin and thermal heat pulses Background and Objectives Mexiletine is an oral sodium channel antagonist that has been reported to be effective in a variety of neuropathic pain syndromes . However , recent reports question the efficacy of oral mexiletine in neuropathic pain . The objectives of this study were to examine the effect of oral mexiletine on pain , neurosensation , allodynia , and quality of life . Methods Twenty subjects suffering from neuropathic pain with prominent allodynia were enrolled in a r and omized placebo-controlled crossover study . Patients were titrated to a maximum dose of 900 mg/d or doselimiting side effects , whichever occurred first . At baseline and on days 0 , 4 , 7 , and 10 , the following tests were performed : ( 1 ) Quality of Life Question naires ; ( 2 ) pain scores ; ( 3 ) area of allodynia ; ( 4 ) side effects ; ( 5 ) neurosensory testing ; and ( 6 ) peak and trough plasma mexiletine levels . Results Peak plasma levels occurred on day 10 and were 0.54 μg/mL. There was no significant effect on any quality of life measurement . There was no significant effect on any neurosensory threshold or the area of allodynia . There was a significant effect of mexiletine on stroking-induced pain . There were no significant effects on any other pain score . Side effects were negligible . Conclusions At doses of up to 900 mg/d , mexiletine has minimal effects on pain and allodynia of neuropathic pain . However , side effects may preclude higher doses & NA ;  Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies & NA ; Ten patients with organic nerve injury causing chronic neuropathic pain were tested for the effects of intravenous lidocaine versus saline upon psychophysical somatosensory variables . The variables assessed were the subjective magnitude of pain , area of mechanical hyperalgesia and presence and magnitude of thermal heat/cold hyperalgesia . The study methods applied to evaluate these conditions were the conventional testing of somatosensory submodalities with area mapping and the subjective magnitude estimation of spontaneous pain . It was found that spontaneous pain and mechanical hyperalgesia were consistently improved , transiently , by intravenous administration of lidocaine in all 10 patients ; areas of hyperalgesia which extended beyond the territory of the nerve also improved transiently . Spontaneous pain and mechanical hyperalgesia , but not hypoesthesia , were transiently improved by injection of saline in only 1 of the 10 patients . This outcome is probably due to a placebo effect . This improvement is in keeping with the inhibition of anomalous neural impulses which can be generated anywhere along the sensory channels responsible for generating spontaneous pain and hyperalgesia . Thus , intravenous lidocaine is proposed as a diagnostic aid in the examination of patients complaining of complex sensory disorders associated with nerve injury . The transient pain relief may allow a fuller identification of the area of sensory loss Severe pain occurs in 5 - 30 % of the spinal cord-injured ( SCI ) population and is difficult to treat . Subarachnoid lidocaine has been used in selected patients with some success . Mexiletine , an analog of lidocaine that acts at Na+/K+ channels in the peripheral nerve , has been found effective in persons with diabetic dysesthetic neuropathy . The effect of mexiletine in the treatment of spinal cord dysesthetic pain was examined in this study . Fifteen patients were enrolled , and 11 patients completed the prospect i ve , r and omized , placebo-controlled , double-blind , crossover design trial . Inclusion /exclusion criteria were carefully defined . A 1-wk washout period was followed by a 4-wk drug trial of either mexiletine ( 450 mg/day ) or placebo . This was repeated for the second medication in the second arm of the study . Patients were followed weekly with McGill and visual analog pain scales . Baseline , midpoint , and endpoint Barthel function scores were recorded . The Wilcoxon 's signed-rank test and paired t test were used for statistical analysis . Results showed no significant effect of mexiletine on SCI dysesthetic pain scales or Barthel index . In conclusion , in this trial , mexiletine did not appear to decrease spinal cord injury-related dysesthetic pain We studied the analgesic efficacy of an intravenous infusion of lidocaine and morphine in 19 adults with well-established postherpetic neuralgia in a three-session , r and omized , double-blind , placebo-controlled trial . Compared with saline placebo , both lidocaine and morphine reduced pain intensity . Reductions in pain did not correlate with side effects produced by the infusions . For morphine , there was a significant correlation between reductions in pain intensity and blood level achieved . In the majority of subjects who reported definite pain relief , allodynia also disappeared . The results show that neuropathic pain can respond to opioids and to systemically administered local anesthetic drugs The objective of this double-blind placebo controlled multicenter study was to prove the efficacy of mexiletine in painful diabetic neuropathy .  Treatment was provided for in three dosages . For pain measurements a visual analogue scale ( VAS ) and McGill 's verbal rating scale were chosen . 95 patients were included . A global assessment of the VAS showed no differences in treatment . The total evaluation ( PRIT = Pain Rating Index Total ) of the McGill scale just failed the level of significance . More specific exploratory evaluation of subclasses of the McGill scale , representing different qualities of pain , gave remarkable differences between mexiletine and placebo . According to types of complaints an evaluation showed substantial advantages of the mexiletine treatment with both the VAS and the McGill scale . There is strong evidence that particularly patients with stabbing  or burning pain  ,  heat sensations  or  formication  will benefit most by mexiletine therapy . Concerning the dosage , a medium regimen of 450 mg per day seems to be appropriate in this indication . With an increase in dosage the efficacy does not rise proportionally . Mexiletine proved 
    Output:
    
In these trials , systemic local anesthetics were safe , with no deaths or life-threatening toxicities .
Lidocaine and oral analogs were safe drugs in controlled clinical trials for neuropathic pain , were better than placebo , and were as effective as other analgesics .
More emphasis is necessary on outcomes measuring patient satisfaction to assess if statistically significant pain relief is clinical ly meaningful