Neurogena upala moždanih ovojnica i bol u području glave i vrata

Filipović, Boris (2016) Neurogena upala moždanih ovojnica i bol u području glave i vrata. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Introduction: Up to now, neurogenic inflammation of dura mater was associated to pathophysiology of migraine pain. The main finding of this doctoral thesis is that pain in the head and neck region elicits dural neurogenic inflammation as well. This phenomenon is caused by the neuropeptides release from the dural sensory neurons and could be prevented by triptans and/or botulinum toxin type A (BoNT/A). Material and methods: Male Wistar rats were used in all experiments. Neurogenic inflammation of cranial dura mater was measured (as plasma protein extravasation and proinflammatory cell infiltration) in models of acute and chronic inflammatory and neuropathic pain in the trigeminal innervation area, and neuropathic pain in the innervation area of major occipital and ischiadic nerve. Additionally, occurrence of neurogenic inflammation of spinal dura was measured in the models of neuropathic pain in the innervation area of ischiadic nerve. The effect of different analgesic drugs (triptans, morphine, local anesthetic) on allodynia and dural neurogenic inflammation was measured in the neuropathic pain model (constriction of the infraorbital nerve). Furthermore we investigated the effect of BoNT/A (s.c. in the whisker pad, 3.5 IJ/kg; i.a. in the temporomandibular joint, 5 IJ/kg; i.g. in the trigeminal ganglion, 2 IJ/kg) on allodynia and dural neurogenic inflammation in the models of acute and chronic inflammatory and neuropathic pain in the trigeminal innervation area. Additionally, we used colchicine (axonal transport inhibitor) to investigate the mechanism of the BoNT/A. Results: Neurogenic inflammation of cranial dura was elicited by inflammatory and neuropathic pain from trigeminal and occipital innervation area. However, neuropathic pain from the innervation area of ischiadic nerve did not result in neurogenic inflammation of cranial and spinal dura mater. Triptans (sumatriptan and zolmitriptan), morphine and local anesthetic decreased both allodynia and dural neurogenic inflammation in the model of trigeminal neuropathic pain. BoNT/A abolished allodynia and dural neurogenic inflammation in the models of acute and chronic inflammatory and neuropathic pain. The effect of BoNT/A was abolished by blocking the axonal transport through trigeminal ganglion. Conclusion: Results of this doctoral thesis indicates that different pain in trigeminal and also occipital area (head and neck region) results in neurogenic inflammation of cranial dura. Antinociceptive mechanism of action of several analgesic and anti-migraine drugs is associated with reduction of dural neurogenic inflammation.

Abstract in Croatian

Uvod: Neurogena upala moždanih ovojnica do sada se povezivala s patofiziologijom migrene. Najvažniji nalaz ove disertacije je da bol različitog podrijetla u području glave i vrata uzrokuje nastanak neurogene upale moždanih ovojnica. To bi moglo biti povezano s izlučivanjem polipetida iz ogranaka senzornih duralnih neurona, što bi trebali spriječiti triptani te botulinum toksin tipa A (BoNT/A). Materijal i metode: Ispitivanja su se provodila na mužjacima štakora soja Wistar. Pojavnost neurogene upale moždanih ovojnica (ekstravazacija plazmatskih proteina i proupalne stanice u duri) ispitivana je na modelima akutne i kronične upalne i neuropatske boli inervacijskog područja n. trigeminusa te neuropatske boli inervacijskog područja n. okcipitalisa major i n. ishijadikusa. Također je ispitivana neurogena upala spinalnih ovojnica nakon neuropatske boli iz inervacije n. ishijadikusa. Ispitivan je učinak pojedinih analgetika (triptani, opioidi, lokalni anestetici) u modelu neuropatske boli podvezivanja infraorbitalnog živaca, na alodiniju i neurogenu upalu dure. Ispitivan je i učinak BoNT/A (s.c. područje brkova, 3,5 i.j/kg; i.a. temporomandibularni zglob, 5 i.j/kg; i.g. trigeminalni ganglij, 2 i.j/kg) na alodiniju i neurogenu upalu u modelima akutne i kronične upalne i neuropatske boli trigeminalne regije. Ispitivan je utjecaj inhibicije aksonalnog transporta kolhicinom na učinak BoNT/A. Rezultati: Neurogene upale moždanih ovojnica se pojavljuju u upalnoj i neuropatskoj boli u području glave i vrata koje je inervirano trigeminalnim i okcipitalnim živcem. Nasuprot tome neuropatska bol (ishijadični živac) nije praćena razvojem neurogene upale spinalnih ovojnica u području kralježničke moždine, a ni upalom kranijalne dure. Triptani (sumatriptan i zolmitriptan), morfin i lokalni anestetici su smanjili alodiniju i neurogenu upalu dure u modelu neuropatske boli. BoNT/A je smanjio alodiniju i neurogenu upalu dure u modelima akutne i kronične upalne i neuropatske boli. Učinak je poništen blokatorom aksonalnog transporta kolhicinom kroz trigeminalni ganglij. Zaključak: Rezultati ove disertacije pokazuju da je različita vrsta boli u trigeminalnoj, a dijelom i u okcipitalnoj regiji (područje glave i vrata) praćena razvojem neurogene upale moždanih ovojnica. Pojedini analgetici i antimigrenozni lijekovi smanjuju bol blokirajući neurogenu upalu dure.

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