title: Cannabinoid agonists inhibit neuropathic pain induced by brachial plexus avulsion in mice by affecting glial cells and MAP kinases.
abstract: BACKGROUND
  Many studies have shown the antinociceptive effects of cannabinoid (CB) agonists in different models of pain. Herein, we have investigated their relevance in neuropathic pain induced by brachial plexus avulsion (BPA) in mice.
  
  
  RESULTS
  Mice underwent BPA or sham surgery. The mRNA levels and protein expression of CB(1) and CB(2) receptors were assessed by RT-PCR and immunohistochemistry, respectively. The activation of glial cells, MAP kinases and transcription factors were evaluated by immunohistochemistry. The antinociceptive properties induced by cannabinoid agonists were assessed on the 5(th) and 30(th) days after surgery. We observed a marked increase in CB(1) and CB(2) receptor mRNA and protein expression in the spinal cord and dorsal root ganglion, either at the 5(th) or 30(th) day after surgery. BPA also induced a marked activation of p38 and JNK MAP kinases (on the 30(th) day), glial cells, such as microglia and astrocytes, and the transcription factors CREB and NF-κB (at the 5(th) and 30(th) days) in the spinal cord. Systemic treatment with cannabinoid agonists reduced mechanical allodynia on both the 5(th) and 30(th) days after surgery, but the greatest results were observed by using central routes of administration, especially at the 30(th) day. Treatment with WIN 55,212-2 prevented the activation of both glial cells and MAP kinases, associated with an enhancement of CREB and NF-κB activation.
  
  
  CONCLUSIONS
  Our results indicate a relevant role for cannabinoid agonists in BPA, reinforcing their potential therapeutic relevance for the management of chronic pain states.
authors.affiliation: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Ana F
authors.initials: AF
authors.lastname: Paszcuk
authors.forename: Rafael C
authors.initials: RC
authors.lastname: Dutra
authors.forename: Kathryn A B S
authors.initials: KA
authors.lastname: da Silva
authors.forename: Nara L M
authors.initials: NL
authors.lastname: Quintão
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines / Q000494:pharmacology; D001917:Brachial Plexus / Q000293:injuries*; D002186:Cannabinoids / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055785:Gene Knockdown Techniques; D006930:Hyperalgesia / Q000150:complications; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D009437:Neuralgia / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059225:Nociception / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D002186:Cannabinoids; D017362:Cyclic AMP Response Element-Binding Protein; D009025:Morpholines; D016328:NF-kappa B; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D020928:Mitogen-Activated Protein Kinases