title: Repeated morphine treatment-mediated hyperalgesia, allodynia and spinal glial activation are blocked by co-administration of a selective cannabinoid receptor type-2 agonist.
abstract: Spinal glial activation has been implicated in sustained morphine-mediated paradoxical pain sensitization. Since activation of glial CB2 cannabinoid receptors attenuates spinal glial activation in neuropathies, we hypothesized that CB2 agonists may also attenuate sustained morphine-mediated spinal glial activation and pain sensitization. Our data indicate that co-administration of a CB2-selective agonist (AM 1241) attenuates morphine (intraperitoneal; twice daily; 6 days)-mediated thermal hyperalgesia and tactile allodynia in rats. A CB2 (AM 630) but not a CB1 (AM 251) antagonist mitigated this effect. AM 1241 co-treatment also attenuated spinal astrocyte and microglial marker and pro-inflammatory mediator (IL-1β, TNFα) immunoreactivities in morphine-treated rats, suggesting that CB2 agonists may be useful to prevent the neuroinflammatory consequences of sustained morphine treatment.
authors.affiliation: Department of Pharmacology, The University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Suneeta
authors.initials: S
authors.lastname: Tumati
authors.forename: Tally M
authors.initials: TM
authors.lastname: Largent-Milnes
authors.forename: Attila
authors.initials: A
authors.lastname: Keresztes
authors.forename: Jiyang
authors.initials: J
authors.lastname: Ren
authors.forename: William R
authors.initials: WR
authors.lastname: Roeske
authors.forename: Todd W
authors.initials: TW
authors.lastname: Vanderah
authors.forename: Eva V
authors.initials: EV
authors.lastname: Varga
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D002186:Cannabinoids / Q000008:administration & dosage; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007211:Indoles / Q000008:administration & dosage*; D007249:Inflammation / Q000188:drug therapy; D053583:Interleukin-1beta / Q000032:analysis; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009457:Neuroglia / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010880:Piperidines / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: C439263:AM 1241; D000700:Analgesics; D000701:Analgesics, Opioid; D002186:Cannabinoids; D007211:Indoles; D053583:Interleukin-1beta; D010880:Piperidines; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D014409:Tumor Necrosis Factor-alpha; C103505:AM 251; D009020:Morphine; C094023:iodopravadoline