title: Postamputation pain and sensory changes in treatment-naive patients: characteristics and responses to treatment with tramadol, amitriptyline, and placebo.
abstract: BACKGROUND
  Pain after amputation is common but difficult to treat, and few controlled treatment studies exist.
  
  
  METHODS
  In the current study, 94 treatment-naive posttraumatic limb amputees with phantom pain (intensity: mean visual analog scale score [0-100], 40 [95% confidence interval, 38-41]) were randomly assigned to receive individually titrated doses of tramadol, placebo (double-blind comparison), or amitriptyline (open comparison) for 1 month. Nonresponders were crossed over to the alternative active treatment.
  
  
  RESULTS
  After 1 month, phantom pain intensity was 1 (0-2) in the 48 tramadol responders (mean dose, 448 mg [95% confidence interval, 391-505 mg]), 0 (0-0) in the 40 amitriptyline responders (55 [50-59] mg), and 0 (0-0) in the 2 placebo responders, with similar effects on stump pain. Cytochrome P-450 2D6 slow metabolizers derived greater analgesia from tramadol and less from amitriptyline compared with fast metabolizers in the first treatment week (P < 0.01). Electrical pain thresholds increased and pain during suprathreshold stimulation decreased markedly on the stump and, to a lesser extent, on the contralateral limb after 1 month of treatment with amitriptyline or tramadol. Adverse effects were minor in all groups, but more common with tramadol.
  
  
  CONCLUSIONS
  In treatment-naive patients, both amitriptyline and tramadol provided excellent and stable phantom limb and stump pain control with no major adverse events. Both drugs demonstrated consistent and large antinociceptive effects on both the stump and the intact limbs.
authors.affiliation: Brain-Gut Research Group, Bern, Switzerland. cws@braingut.com
authors.forename: Clive H
authors.initials: CH
authors.lastname: Wilder-Smith
authors.forename: Lauren T
authors.initials: LT
authors.lastname: Hill
authors.forename: Sophie
authors.initials: S
authors.lastname: Laurent
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000639:Amitriptyline / Q000627:therapeutic use*; D000672:Amputation Stumps / Q000503:physiopathology*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D017288:Pain Threshold; D010591:Phantom Limb / Q000188:drug therapy*; D010641:Phenotype; D014147:Tramadol / Q000627:therapeutic use*
chemical_list: D000639:Amitriptyline; D014147:Tramadol; D019389:Cytochrome P-450 CYP2D6