title: A pilot open-label study of the efficacy of subanesthetic isomeric S(+)-ketamine in refractory CRPS patients.
abstract: OBJECTIVE
  Complex regional pain syndrome (CRPS) is a severe neuropathic pain state that is often disproportionate to the initial trauma. Associated features are autonomic dysregulation, swelling, motor dysfunction, and trophic changes to varying degrees. Despite a multitude of treatment modalities, a subgroup of CRPS patients remain refractory to all standard therapies. In these patients, the disease may spread extraterritorially, which results in severe disability. A critical involvement of N-methyl-D-aspartate receptors (NMDARs) has been demonstrated both clinically and by animal experimentation. NMDA antagonists may be effective in many neuropathic pain states. In long-standing, generalized CRPS, we investigated the effects of S(+)-ketamine on pain relief and somatosensory features, assessed by quantitative sensory testing (QST).
  
  
  METHODS
  Four refractory CRPS patients received continous S(+)-ketamine-infusions, gradually titrated (50 mg/day-500 mg/day) over a 10-day period. Pain intensities (average, peak, and least pain) and side effects were rated on visual analogue scales, during a 4-day baseline, over 10 treatment days, and 2 days following treatment. QST (thermo-, mechanical detection, and pain thresholds) was analyzed at baseline and following treatment.
  
  
  RESULTS
  Subanesthetic S(+)-ketamine showed no reduction of pain and effected no change in thermo- and mechanical detection or pain thresholds. This procedure caused no relevant side effects. The lack of therapeutic response in the first four patients led to termination of this pilot study.
  
  
  CONCLUSIONS
  S(+)-ketamine can be gradually titrated to large doses (500 mg/day) without clinically relevant side effects. There was no pain relief or change in QST measurements in this series of long-standing severe CRPS patients.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Ralph-Thomas
authors.initials: RT
authors.lastname: Kiefer
authors.forename: Peter
authors.initials: P
authors.lastname: Rohr
authors.forename: Annette
authors.initials: A
authors.lastname: Ploppa
authors.forename: Boris
authors.initials: B
authors.lastname: Nohé
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Dieterich
authors.forename: John
authors.initials: J
authors.lastname: Grothusen
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Altemeyer
authors.forename: Klaus
authors.initials: K
authors.lastname: Unertl
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schwartzman
mesh_terms: D000293:Adolescent; D000328:Adult; D000778:Anesthetics, Dissociative / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D020918:Complex Regional Pain Syndromes / Q000188:drug therapy*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007649:Ketamine / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010865:Pilot Projects; D011446:Prospective Studies; D012684:Sensory Thresholds / Q000187:drug effects; D013237:Stereoisomerism; D013697:Thermosensing / Q000187:drug effects
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine