title: Central action of peripherally applied botulinum toxin type A on pain and dural protein extravasation in rat model of trigeminal neuropathy.
abstract: BACKGROUND
  Infraorbital nerve constriction (IoNC) is an experimental model of trigeminal neuropathy. We investigated if IoNC is accompanied by dural extravasation and if botulinum toxin type A (BoNT/A) can reduce pain and dural extravasation in this model.
  
  
  RESULTS
  Rats which developed mechanical allodynia 14 days after the IoNC were injected with BoNT/A (3.5 U/kg) into vibrissal pad. Allodynia was tested by von Frey filaments and dural extravasation was measured as colorimetric absorbance of Evans blue-plasma protein complexes. Presence of dural extravasation was also examined in orofacial formalin-induced pain. Unilateral IoNC, as well as formalin injection, produced bilateral dural extravasation. Single unilateral BoNT/A injection bilaterally reduced IoNC induced dural extravasation, as well as allodynia (lasting more than 2 weeks). Similarly, BoNT/A reduced formalin-induced pain and dural extravasation. Effects of BoNT/A on pain and dural extravasation in IoNC model were dependent on axonal transport through sensory neurons, as evidenced by colchicine injections (5 mM, 2 µl) into the trigeminal ganglion completely preventing BoNT/A effects.
  
  
  CONCLUSIONS
  Two different types of pain, IoNC and formalin, are accompanied by dural extravasation. The lasting effect of a unilateral injection of BoNT/A in experimental animals suggests that BoNT/A might have a long-term beneficial effect in craniofacial pain associated with dural neurogenic inflammation. Bilateral effects of BoNT/A and dependence on retrograde axonal transport suggest a central site of its action.
authors.affiliation: Laboratory of Molecular Neuropharmacology, Department of Pharmacology and Croatian Brain Research Institute, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Boris
authors.initials: B
authors.lastname: Filipović
authors.forename: Ivica
authors.initials: I
authors.lastname: Matak
authors.forename: Lidija
authors.initials: L
authors.lastname: Bach-Rojecky
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Lacković
mesh_terms: D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D002490:Central Nervous System / Q000187:drug effects*; D004195:Disease Models, Animal; D004388:Dura Mater / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects; D020433:Trigeminal Nerve Diseases / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000700:Analgesics; D009419:Nerve Tissue Proteins; D019274:Botulinum Toxins, Type A