Central action of peripherally applied botulinum toxin type a on pain and dural protein extravasation in rat model of trigeminal neuropathy

Filipović, Boris and Matak, Ivica and Bach-Rojecky, Lidija and Lacković, Zdravko (2012) Central action of peripherally applied botulinum toxin type a on pain and dural protein extravasation in rat model of trigeminal neuropathy. PLoS One, 7 (1). e29803. ISSN 1932-6203

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Official URL: https://doi.org/10.1371/journal.pone.0029803

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. ----- METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.

Item Type:

Article

MeSH:

Analgesics / administration & dosage ; Animals ; Botulinum Toxins, Type A / administration & dosage ; Central Nervous System / drug effects ; Disease Models, Animal ; Dura Mater / drug effects ; Dura Mater / metabolism ; Injections, Intraperitoneal ; Male ; Nerve Tissue Proteins / metabolism ; Pain / drug therapy ; Rats ; Rats, Wistar ; Sensory Receptor Cells / drug effects ; Trigeminal Nerve Diseases / drug therapy ; Trigeminal Nerve Diseases / pathology

Departments:

Hrvatski institut za istraživanje mozga
Katedra za farmakologiju

Depositing User:

Marijan Šember

Status:

Published

Creators: