Meningeal extravasation, efficacy of botulinum toxin or triptans is not specific for pathophysiology of migraine only

[Speaker] Zdravko Lackovic:1
[Co-author] Ivica Matak:1, Boris Filipovic:2, Visnja Drinovac-Vlah:3, Lidija Bach-Rojecky:3
1:Pharmacology, University of Zagreb, School of Medicine, Croatia, 2:Clinical Hospital ‘Sveti Duh’, Croatia, 3:Pharmacology, University of Zagreb, School of Pharmacy and Biochemistry, Croatia

Background: Dural neurogenic inflammation (DNI) is generally recognized as important event in pathophysiology of migraine pain. However, we discovered that in rat DNI, consisting of plasma protein extravasation and inflammatory cells infiltration, can be evoked by different forms of pain in trigeminal area like formalin injection; infraorbital nerve constriction injury or temporomandibular joint inflammation (Filipovic at al J Neural Transm 2014, Lackovic at al Br J Pharmacol. 2016). Here we tested duration of DNI and the effects of different analgesic drugs.
Methods: Experimental pain was induced by chronic constriction injury to the left infraorbital nerve, or by formalin injection nasolabial (vibrissae) region. Allodynia was tested by von Frey filaments and dural extravasation was measured as colorimetric absorbance of Evans blue-plasma protein complexes. Dural infiltration with inflammatory cells was examined histologically. Tracing botulinum toxin enzymatic activity was performed by immunohistochemistry of its product i.e. cleaved SNAP25.
Results: After formalin injection, infraorbital nerve constriction injury rats developed mechanical allodynia and DNI. Duration of DNI was clearly associated with duration of allodynia. Morphine or paracetamol, but also botulinum toxin type A or triptans prevented allodynia and DNI. Botulinum toxin type A enzymatic activity, i.e. presence of cleaved SNAP25 in nerve elements of dura mater collocalised with calcitonin gene related polypeptide (CGRP).
Conclusion: Widely accepted understanding that neurogenic inflammation of meninges is an essential event in the pathophysiology of migraine pain, should be expanded. DNI apparently participates in the pathophysiology of various types of pain in trigeminal region. Present results suggest that that medications that reduce neurogenic inflammation should be effective in treatment of different headaches and other pain conditions in the trigeminal region.
Supported by: Croatian Science Foundation (no. IP-2014-09-4503; BrainTox) and University of Zagreb

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