Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial.

BACKGROUND: Stump and phantom pains are debilitating sequelae of amputations that are often resistant to treatment. The efficacy of pharmacologic therapies, including opioids and sodium channel blockers, for postamputation pain is uncertain. METHODS: The authors conducted a double-blind, randomized, placebo-controlled, crossover study in adult patients with postamputation pain of 6 months or longer and greater than 3 on a 0-10 numeric pain rating scale. Each of the three treatment periods (morphine, mexiletine, or placebo) included a 1-week drug-free interval followed by 4-week titration, 2-week maintenance, and 2-week drug-taper phases. The primary outcome measure was change in average pain intensity from the drug-free baseline to the last week of maintenance. RESULTS: Sixty amputees were enrolled; data were analyzed from 56 subjects for one drug period, 45 subjects for two drug periods, and 35 subjects who completed all three drug periods. The mean morphine and mexiletine dosages were 112 and 933 mg, respectively. Morphine treatment provided lower pain scores compared with placebo and mexiletine (P = 0.0003). The mean percent pain relief during treatment with placebo, mexiletine, and morphine was 19, 30, and 53%, respectively (P < 0.0001, morphine vs. placebo and mexiletine). The numbers needed to treat to obtain 50% and 33% decreases in pain intensity with morphine were 5.6 and 4.5, respectively. Treatment with morphine was associated with a higher rate of side effects. CONCLUSIONS: Therapy with morphine, but not mexiletine, resulted in a decrease in intensity of postamputation pain but was associated with a higher rate of side effects and no improvement in self-reported levels of overall functional activity and pain-related interference in daily activities.

Spinal cord stimulation for complex regional pain syndrome: an evidence-based medicine review of the literature.

OBJECTIVES: The purpose of this investigation is to assess the evidence for efficacy of SCS in the management of pain in patients with CRPS. SEARCH STRATEGY: Electronic databases such as Medline and Cochrane Library were queried using key words such as "spinal cord stimulation," "reflex sympathetic dystrophy (RSD)," and "complex regional pain syndrome (CRPS)." SELECTION CRITERIA: Relevant published randomized controlled trials (RCT), cohort studies, case-control studies, case series, and case reports that described SCS as the primary treatment modality for patients with CRPS were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Data extracted from qualified studies were summarized in sections of methodology, demographics, SCS equipment, primary and secondary outcomes, and complications. RESULTS: Thirteen studies using the primary search strategy and 7 studies from their reference lists were considered. Five of these 20 studies were discarded. One RCT, 2 prospective observational, and 12 retrospective observational studies were eventually considered. The methodological quality of all studies was poor except for the single RCT study. DISCUSSION: Although limited in quality and quantity, available evidence from the examined literature suggests that SCS is effective in the management of pain in patients with CRPS (grade B/C). Clinically useful information extracted from the available studies is very limited in guiding clinicians in the rational use of SCS for pain management in CRPS patients. Future attempts to investigate the efficacy of SCS in CRPS patients should involve methodologically robust designs such as randomized studies that have sufficient power.