title: Cyclotraxin-B, a new TrkB antagonist, and glial blockade by propentofylline, equally prevent and reverse cold allodynia induced by BDNF or partial infraorbital nerve constriction in mice.
abstract: Several lines of evidence indicate that brain-derived neurotrophic factor (BDNF) plays a key role as a central pronociceptive modulator of pain, acting through postsynaptic TrkB receptors that trigger intracellular signaling cascades leading to central sensitization. The overall aim of this study was to investigate to what extent BDNF could participate in the generation and maintenance of trigeminal neuropathic pain. The results showed that acute intracisternal administration of nanogram doses of BDNF in naïve mice elicited long-lasting, dose-related, cold allodynic responses to topical application of acetone onto vibrissal pad skin. The systemic administration of cyclotraxin-B (CTX-B), a new TrkB receptor antagonist, or propentofylline, an inhibitor of glial activation, was able to either prevent or reverse the effects of intracisternal BDNF on cold nociception. In addition, the blockade of TrkB receptor by CTX-B inhibited the mechanisms that either initiate or maintain cold allodynia in the ipsilateral vibrissal pad skin after unilateral constriction of the infraorbital nerve. These observations raise the possibility that BDNF is capable on its own of conveying many features of the signaling mechanisms that underlie central sensitization caused by nerve constriction.
  
  
  CONCLUSIONS
  Although further studies are necessary to examine in detail the mechanisms underlying the strong anti-allodynic action of CTX-B, this compound may represent an interesting lead for the development of novel therapeutic strategies aimed at preventing and/or suppressing central sensitization associated with neuropathic pain.
authors.affiliation: Laboratorio de Neurobiología, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Constandil
authors.forename: Mariela
authors.initials: M
authors.lastname: Goich
authors.forename: Alejandro
authors.initials: A
authors.lastname: Hernández
authors.forename: Laurence
authors.initials: L
authors.lastname: Bourgeais
authors.forename: Maxime
authors.initials: M
authors.lastname: Cazorla
authors.forename: Michel
authors.initials: M
authors.lastname: Hamon
authors.forename: Luis
authors.initials: L
authors.lastname: Villanueva
authors.forename: Teresa
authors.initials: T
authors.lastname: Pelissier
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D059333:Central Nervous System Sensitization / Q000187:drug effects / Q000502:physiology; D003080:Cold Temperature; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000378:metabolism* / Q000517:prevention & control; D009457:Neuroglia / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D020813:Receptor, trkB / Q000037:antagonists & inhibitors*; D014277:Trigeminal Neuralgia / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D010456:Peptides, Cyclic; D014970:Xanthines; C554840:cyclotraxin-B; C032114:propentofylline; D020813:Receptor, trkB