Analgesic Mechanisms in Patients with Chronic and Acute Postoperative Pain

Max, M.

Abstract

The purpose of this project is to elucidate the principles of treatment of acute and chronic pain syndromes, with particular attention to the drug treatment of pain caused by nerve injury. In an interim analysis of a double-blind, crossover study in 22 patients with painful diabetic neuropathy, 7 patients obtained significantly better pain relief with clonidine than placebo and had that response confirmed by two subsequent double-blind crossover comparisons of clonidine and placebo. Clonidine is ana2-adrenergic agonist commonly used as an antihypertensive. This confirms the result of a previous trial showing that a subset of patients were clonidine-responsive, and suggests that clonidine may be a useful advance in treatment for a subset of patients with neuropathic pain. Because of growing evidence from animal studies that neuropathic pain may be mediated by spinal cord neurons depolarized by NMDA channels, the NMDA antagonist ketamine is being studied in two conditions: chronic pain in patients with nerve damage or reflex sympathetic dystrophy, and normal volunteers with hyperalgesia of the skin briefly induced by intradermal injection of capsaicin.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Dental & Craniofacial Research (NIDCR)
• Type: Intramural Research (Z01)
• Project #: 1Z01DE000366-10
• Application #: 3839196
• Support Year: 10
• Fiscal Year: 1992

Institution

• Name: National Institute of Dental & Craniofacial Research
• Country: United States

Publications

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