Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds.
BACKGROUND
Calcitonin was effective in a study of acute phantom limb pain, but it was not studied in the chronic phase. The overall literature on N-methyl-D-aspartate antagonists is equivocal. We tested the hypothesis that calcitonin, ketamine, and their combination are effective in treating chronic phantom limb pain. Our secondary aim was to improve our understanding of the mechanisms of action of the investigated drugs using quantitative sensory testing.


METHODS
Twenty patients received, in a randomized, double-blind, crossover manner, 4 i.v. infusions of: 200 IE calcitonin; ketamine 0.4 mg/kg (only 10 patients); 200 IE of calcitonin combined with ketamine 0.4 mg/kg; placebo, 0.9% saline. Intensity of phantom pain (visual analog scale) was recorded before, during, at the end, and the 48 h after each infusion. Pain thresholds after electrical, thermal, and pressure stimulation were recorded before and during each infusion.


RESULTS
Ketamine, but not calcitonin, reduced phantom limb pain. The combination was not superior to ketamine alone. There was no difference in basal pain thresholds between the amputated and contralateral side except for pressure pain. Pain thresholds were unaffected by calcitonin. The analgesic effect of the combination of calcitonin and ketamine was associated with a significant increase in electrical thresholds, but with no change in pressure and heat thresholds.


CONCLUSIONS
Our results question the usefulness of calcitonin in chronic phantom limb pain and stress the potential interest of N-methyl-D-aspartate antagonists. Sensory assessments indicated that peripheral mechanisms are unlikely important determinants of phantom limb pain. Ketamine, but not calcitonin, affects central sensitization processes that are probably involved in the pathophysiology of phantom limb pain.
Eichenberger
Urs
U
Department of Anesthesiology, Division of Pain Therapy, University Hospital of Bern, Inselspital, 3010 Bern, Switzerland. urs.eichenberger@insel.ch
Neff
Frank
F
Sveticic
Gorazd
G
Björgo
Steinar
S
Petersen-Felix
Steen
S
Arendt-Nielsen
Lars
L
Curatolo
Michele
M
D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D002116:Calcitonin / Q000008:administration & dosage / Q000627:therapeutic use*; D003201:Computers; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004558:Electric Stimulation; D006358:Hot Temperature; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010465:Perception; D010591:Phantom Limb; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D007649:Ketamine; D002116:Calcitonin