title: Neuropathic and chronic pain stimuli downregulate central mu-opioid and dopaminergic transmission.
abstract: Although morphine and other mu-opioid agonists are the main analgesics for severe pain, these compounds have potential for abuse and/or addiction. This has complicated the use of mu-agonists in the treatment of chronic pain. However, clinical studies show that when mu-agonist analgesics are appropriately used to control pain, actual abuse or addiction does not usually occur, although some risk factors that increase vulnerability need to be considered, including genetic variation. We review recent findings on molecular adaptations in sustained pain models, and propose how these adaptations (including sustained release of the endogenous mu-agonist beta-endorphin) can result in decreased abuse potential of mu-agonists in chronic pain states. We also review data on particular gene polymorphisms (e.g. in the mu-receptor gene) that could also influence the relative abuse potential of mu-agonists in clinical pain populations.
authors.affiliation: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Niikura
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Butelman
authors.forename: Mary Jeanne
authors.initials: MJ
authors.lastname: Kreek
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D002908:Chronic Disease; D015536:Down-Regulation; D004399:Dynorphins / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D009293:Opioid-Related Disorders / Q000209:etiology*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D012201:Reward; D015854:Up-Regulation; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D004723:Endorphins; C485764:OPRM1 protein, human; D011954:Receptors, Dopamine; D017450:Receptors, Opioid, mu; D004399:Dynorphins; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases