title: Managing chronic whiplash associated pain with a combination of low-dose opioid (remifentanil) and NMDA-antagonist (ketamine).
abstract: The aim was to investigate the efficacy of a combination of low-dose remifentanil (REMI) and ketamine (KET) compared to the single drugs and placebo (P) on whiplash associated pain (WAD) in a double-blind, randomized, placebo-controlled, cross-over study. Twenty patients with chronic (>1 year) WAD were included. Four different drug combinations were tested in four sessions: placebo/placebo (P/P), placebo/remifentanil (P/REMI), ketamine/placebo (KET/P) and ketamine/remifentanil (KET/REMI). Target concentrations were 1 and 2ng/ml (stepwise) for remifentanil and 100ng/ml for ketamine. Habitual pain intensity was assessed on a visual analogue scale (VAS). Experimental pain was assessed with electrical stimulation (single and repeated) of tibialis anterior (TA) muscle, pressure pain algometry applied over infraspinatus (IS) and TA muscles and VAS scores after intramuscular hypertonic saline infusion in TA. KET/REMI significantly reduced habitual pain. KET/REMI infused at low REMI target concentration (1ng/ml) significantly elevated electrical intramuscular pain thresholds (single and repeated). Pain thresholds to electrical stimulation were similarly increased by both P/REMI and KET/REMI at 2ng/ml target concentration. Pressure pain thresholds were increased by both KET/REMI and P/REMI. VAS-scores after intramuscular saline were also similarly decreased by both REMI combinations. Seven out of 20 subjects were non-responders (<50% pain relief). No correlation was found between effects on spontaneous pain and experimental pain. KET/REMI showed an analgesic effect on habitual pain. Experimental pain was attenuated by both combinations containing the opioid, however, KET seemed to enhance the effect of REMI on electrical pain thresholds when a low REMI target concentration was used.
authors.affiliation: Pain and Rehabilitation Centre, University Hospital, Linköping, Sweden.
authors.forename: Dag
authors.initials: D
authors.lastname: Lemming
authors.forename: Jan
authors.initials: J
authors.lastname: Sörensen
authors.forename: Thomas
authors.initials: T
authors.lastname: Graven-Nielsen
authors.forename: Rolf
authors.initials: R
authors.lastname: Lauber
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.forename: Björn
authors.initials: B
authors.lastname: Gerdle
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019547:Neck Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D011312:Pressure; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D000077208:Remifentanil; D012965:Sodium Chloride; D014911:Whiplash Injuries / Q000150:complications*
chemical_list: D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D012965:Sodium Chloride; D007649:Ketamine; D000077208:Remifentanil