Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain

• Pain Intensity [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

  McGill short form pain questionnaire (SF MPQ)will be completed twice daily during the following time points: 2 weeks before taking study medication, 6 weeks during study medication, and 2 weeks after discontinuation of study medication.

  The visual analog scale (VAS) pain rating will serve as the study's primary outcome measure.

  
  

• Change from baseline disability measures at 10 weeks [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

  The McGill short form pain questionnaire (SF MPQ) and the Profile of Mood States-Short Form (POMS-SF) will be completed twice daily during the following time points: 2 weeks before taking study medication, 6 weeks during study medication, and 2 weeks after discontinuation of study medication.

  Outcome responses from the questionnaires will be examined using General Linear Models (GLM), examining for differences in group either at one time period or as a function of study phase, as appropriate.

  
  
• Change from baseline psychometric measures at 10 weeks [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

  The Profile of Mood States-Short Form (POMS-SF) will be completed twice daily during the following time points: 2 weeks before taking study medication, 6 weeks during study medication, and 2 weeks after discontinuation of study medication.

  Outcome responses from the questionnaires will be examined using General Linear Models (GLM), examining for differences in group either at one time period or as a function of study phase, as appropriate.

  
  
• Change from baseline global assessments at 10 weeks [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

  The McGill short form pain questionnaire (SF MPQ) and the Profile of Mood States-Short Form (POMS-SF) will be completed twice daily during the following time points: 2 weeks before taking study medication, 6 weeks during study medication, and 2 weeks after discontinuation of study medication.

  Outcome responses from the questionnaires will be examined using General Linear Models (GLM), examining for differences in group either at one time period or as a function of study phase, as appropriate.

  
  
• Change from baseline rescue medication use at 10 weeks [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

  Questionnaires detailing the amount of rescue pain medications will be completed twice daily during the following time points: 2 weeks before taking study medication, 6 weeks during study medication, and 2 weeks after discontinuation of study medication.

  Outcome responses from the questionnaires will be examined using General Linear Models (GLM), examining for differences in group either at one time period or as a function of study phase, as appropriate.

  
  

Investigators are currently examining in the laboratory the mechanisms which lead to sprouting of noradrenergic fibers in the spinal cord in models of chronic pain as well as the mechanisms that lead to a novel noradrenergic - cholinergic circuit in the spinal cord. In addition to examining the circumstances which generate this increased capacity for analgesia and the mechanisms by which they occur, investigators will test in this protocol whether approved and experimental treatments for neuropathic pain exploit this increased capacity.

This study is in patients with neuropathic pain taking gabapentin or pregabalin, and will test the clinical relevance of these preclinical data by comparing placebo to the cholinesterase inhibitor. Investigators focus not only on mechanistic hypotheses in the laboratory studies, but also on practical applications, using clinically approved drugs, including gabapentin and pregabalin to activate noradrenergic activity and donepezil (Aricept®), approved for the treatment of Alzheimer's dementia, but not previously tested to treat neuropathic pain, to inhibit cholinesterase. Each of these drugs may act by mechanisms in addition to those involved in descending noradrenergic inhibition, but investigators hypothesize that the therapeutic strength of their combination relies heavily on this cascade engendered by noradrenergic sprouting and altered α2-adrenoceptor function. The proposed studies will provide critical tests of this hypothesis and critical information to guide more effective clinical therapy of neuropathic pain.