title: Cannabinoid CB(2)  receptor attenuates morphine-induced inflammatory responses in activated microglial cells.
abstract: OBJECTIVE
  Among several pharmacological properties, analgesia is the most common feature shared by either opioid or cannabinoid systems. Cannabinoids and opioids are distinct drug classes that have been historically used separately or in combination to treat different pain states. In the present study, we characterized the signal transduction pathways mediated by cannabinoid CB(2) and µ-opioid receptors in quiescent and LPS-stimulated murine microglial cells.
  
  
  METHODS
  We examined the effects of µ-opioid and CB(2) receptor stimulation on phosphorylation of MAPKs and Akt and on IL-1β, TNF-α, IL-6 and NO production in primary mouse microglial cells.
  
  
  RESULTS
  Morphine enhanced release of the proinflammatory cytokines, IL-1β, TNF-α, IL-6, and of NO via µ-opioid receptor in activated microglial cells. In contrast, CB(2) receptor stimulation attenuated morphine-induced microglial proinflammatory mediator increases, interfering with morphine action by acting on the Akt-ERK1/2 signalling pathway.
  
  
  CONCLUSIONS
  Because glial activation opposes opioid analgesia and enhances opioid tolerance and dependence, we suggest that CB(2) receptors, by inhibiting microglial activity, may be potential targets to increase clinical efficacy of opioids.
authors.affiliation: Department of Clinical and Experimental Medicine, Pharmacology Section and Interdisciplinary Center for the Study of Inflammation, University of Ferrara, Ferrara, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Merighi
authors.forename: Stefania
authors.initials: S
authors.lastname: Gessi
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Debora
authors.initials: D
authors.lastname: Fazzi
authors.forename: Prisco
authors.initials: P
authors.lastname: Mirandola
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology*; D009284:Naphthols; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014227:Triazines
chemical_list: C409762:2-(3-aminophenol)-6-(4-amino-1-naphthol)-4-chloro-triazine; D016207:Cytokines; D007211:Indoles; D008070:Lipopolysaccharides; D009284:Naphthols; D009573:Nitrites; D034741:RNA, Small Interfering; D043885:Receptor, Cannabinoid, CB2; D017450:Receptors, Opioid, mu; D014227:Triazines; D009569:Nitric Oxide; D009020:Morphine; D048369:MAP Kinase Kinase 1; C402944:JHW 015