The purpose of this work is to evaluate drug therapy in chronic pain syndromes that are considered resistant to known approaches such as pain caused by nerve injury and by advanced cancer. The first study in this series has shown that amitriptyline relieves diabetic neuropathy pain in patients with normal as well as depressed mood. Twenty-nine patients received 6 weeks of amitriptyline (25-150 mg at bedtime, to maximum tolerated) and 6 weeks of a placebo chosen to mimic amitriptyline side-effects, in a crossover design. Patients' global evaluations after treatment periods indicated that 23 had less pain with amitriptyline, 1 had less pain with placebo, and 5 had similar levels of pain with the two drugs. Amitriptyline was more analgesic than placebo in both the 15 non-depressed patients and in the 14 depressed patients. We conclude that amitriptyline has an analgesic action in diabetic neuropathy that is independet of its antidepressant effects. In 409 patients with post-herpetic neuralgia, a comparison of single doses of clonidine, codeine, and ibuprofen to placebo did not demonstrate a specific analgesic effect for any drug. It was shown that with drug or placebo, patients report more pain relief when they detect side-effects, which has implications for analgesic trial design and clinical treatment. Thirty-two of a projected 40 post-herpetic neuralgia patients have completed a study of chronic amitriptyline vs. lorazepam vs. placebo; an interim analysis showed that amitriptyline was a superior analgesic to the other two treatments. A study of the delta opiate agonist metkephamid in cancer patients with varying degrees of tolerance at the mu or morphine receptor was suspended because of drug side-effects. Resumption awaits the availability of other investigational delta or kappa receptor opiates.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000366-03
Application #
4692646
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Slade, Gary D; Diatchenko, Luda; Ohrbach, Richard et al. (2008) Orthodontic Treatment, Genetic Factors and Risk of Temporomandibular Disorder. Semin Orthod 14:146-156
Lotsch, Jorn; Belfer, Inna; Kirchhof, Anja et al. (2007) Reliable screening for a pain-protective haplotype in the GTP cyclohydrolase 1 gene (GCH1) through the use of 3 or fewer single nucleotide polymorphisms. Clin Chem 53:1010-5
Khoromi, Suzan; Blackman, Marc R; Kingman, Albert et al. (2007) Low intensity permanent magnets in the treatment of chronic lumbar radicular pain. J Pain Symptom Manage 34:434-45
Belfer, I; Hipp, H; Bollettino, A et al. (2007) Alcoholism is associated with GALR3 but not two other galanin receptor genes. Genes Brain Behav 6:473-81
Khoromi, Suzan; Cui, Lihong; Nackers, Lisa et al. (2007) Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain. Pain 130:66-75
Edwards, Robert R; Klick, Brendan; Buenaver, Luis et al. (2007) Symptoms of distress as prospective predictors of pain-related sciatica treatment outcomes. Pain 130:47-55
Diatchenko, Luda; Anderson, Amy D; Slade, Gary D et al. (2006) Three major haplotypes of the beta2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder. Am J Med Genet B Neuropsychiatr Genet 141B:449-62
Diatchenko, Luda; Nackley, Andrea G; Slade, Gary D et al. (2006) Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli. Pain 125:216-24
Farrar, John T; Dworkin, Robert H; Max, Mitchell B (2006) Use of the cumulative proportion of responders analysis graph to present pain data over a range of cut-off points: making clinical trial data more understandable. J Pain Symptom Manage 31:369-77
Max, Mitchell B; Wu, Tianxia; Atlas, Steven J et al. (2006) A clinical genetic method to identify mechanisms by which pain causes depression and anxiety. Mol Pain 2:14

Showing the most recent 10 out of 43 publications