engleski

Botulinum toxin A in a rat model of migraine and/or trigeminal neuropathy

There is an increasing number of clinical observations and few preclinical experiments showing that botulinum toxin type B (BTX-A) might have significant and long-lasting antinociceptive effect in both humans and animals. Its use was reported to be useful in relieving symptoms of chronic pain states like tension-type headaches, peripheral neuropathies and migraine. In this work we wanted to assess the effects of a single unilateral injection of botulinum toxin type A (BoNT/A, 3.5 U/kg) on mechanical allodynia and dural extravasation induced by infraorbital nerve constriction injury (IoNC) in rats. Male Wistar rats were operated and infraorbital nerve was constricted. After two weeks BoNT/A was administered into whisker pad either ipsilaterally or contralaterally to the side of nerve injury. In one experiment the effect of BoNT/A on bilateral pain was assessed for a period of month by measuring mechanical allodynia using the von Frey filaments. In a second experiment, animals which developed mechanical allodynia were administered with Evans blue intravenously and bilateral dural extravasation of Evans blue - plasma protein complexes was assessed. Mechanical allodynia was reduced by a single BoNT/A injection on the side of the toxin injection, and on the opposite side, as well. The antinociceptive effect started on day 3 following the toxin application and lasted for at least 17 more days. IoNC-induced neuropathy elicited significant bilateral increase in dural extravasation of plasma proteins. Additionally, BoNT/A completely abolished increased dural extravasation on both sides. BoNT/A was effective on both allodynia and dural extravasation regardless of whether the site of injection was ipsilateral or contralateral to the site of nerve injury. Lasting reduction of bilateral mechanical allodynia by a single peripheral unilateral BoNT/A injection, together with the abolished dural protein extravasation, confirm central site of the BoNT/A antinociceptive action.

botulinum toxin; trigeminal neuropathy; dural extravasation

Acknowledgements: This work was supported by Croatian Ministry of Science, Education and Sport, (Project No. 108-1080003-0001) and Deutsche Academische Austauch Dienst (DAAD).