Abstract:
BACKGROUND AND PURPOSE:Although botulinum toxin type A (BoNT/A) is approved for chronic migraine treatment, its mechanism of action is still unknown. Dural neurogenic inflammation (DNI) commonly used to investigate migraine pathophysiology can be evoked by trigeminal pain. Here, we investigated the reactivity of cranial dura to trigeminal pain and the mechanism of BoNT/A action on DNI. EXPERIMENTAL APPROACH:Because temporomandibular disorders are highly comorbid with migraine, we employed a rat model of inflammation induced by complete Freund's adjuvant, followed by treatment with BoNT/A injections or sumatriptan p.o. DNI was assessed by Evans blue-plasma protein extravasation, cell histology and RIA for CGRP. BoNT/A enzymatic activity in dura was assessed by immunohistochemistry for cleaved synaptosomal-associated protein 25 (SNAP-25). KEY RESULTS:BoNT/A and sumatriptan reduced the mechanical allodynia and DNI, evoked by complete Freund's adjuvant. BoNT/A prevented inflammatory cell infiltration and inhibited the increase of CGRP levels in dura. After peripheral application, BoNT/A-cleaved SNAP-25 colocalized with CGRP in intracranial dural nerve endings. Injection of the axonal transport blocker colchicine into the trigeminal ganglion prevented the formation of cleaved SNAP-25 in dura. CONCLUSIONS AND IMPLICATIONS:Pericranially injected BoNT/A was taken up by local sensory nerve endings, axonally transported to the trigeminal ganglion and transcytosed to dural afferents. Colocalization of cleaved SNAP-25 and the migraine mediator CGRP in dura suggests that BoNT/A may prevent DNI by suppressing transmission by CGRP. This might explain the effects of BoNT/A in temporomandibular joint inflammation and in migraine and some other headaches.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Lacković Z,Filipović B,Matak I,Helyes Zdoi
10.1111/bph.13366subject
Has Abstractpub_date
2016-01-01 00:00:00pages
279-91issue
2eissn
0007-1188issn
1476-5381journal_volume
173pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:The effects of systemic treatment with indomethacin-loaded nanocapsules (IndOH-NC) were compared with those of free indomethacin (IndOH) in rat models of acute and chronic oedema. EXPERIMENTAL APPROACH:The following models of inflammation were employed: carrageenan-induced acute oedema (measured...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.2009.00244.x
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abstract:BACKGROUND AND PURPOSE:Voltage-operated sodium channels constitute major target sites for local anaesthetic-like action. The clinical use of local anaesthetics is still limited by severe side effects, in particular, arrhythmias and convulsions. These side effects render the search for new local anaesthetics a matter of...
journal_title:British journal of pharmacology
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doi:10.1038/bjp.2008.255
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doi:10.1111/j.1476-5381.1994.tb13121.x
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journal_title:British journal of pharmacology
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doi:10.1038/bjp.2008.86
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journal_title:British journal of pharmacology
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abstract:BACKGROUND AND PURPOSE:We have developed a strategy to target the permanently charged lidocaine derivative lidocaine N-ethyl bromide (QX-314) selectively into nociceptive sensory neurons through the large-pore transient receptor potential cation channel subfamily V (TRPV1) noxious heat detector channel. This involves c...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.2011.01391.x
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Although the stoichiometry of the major synaptic αβγ subunit-containing GABAA receptors has consensus support for 2α:2β:1γ, a clear view of the stoichiometry of extrasynaptic receptors containing δ subunits has remained elusive. Here we examine the subunit stoichiometry of recombinant α4β3δ recep...
journal_title:British journal of pharmacology
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abstract::1. Changes in cutaneous water loss were followed by continuously monitoring total body weight loss.2. Sweating was induced in normal subjects by raising the environmental temperature or by subjecting them to the emotional stress of mental arithmetic.3. Propranolol in a dosage of 0.15 mg/kg body weight intravenously ha...
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pub_type: 杂志文章
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更新日期:1973-03-01 00:00:00
abstract::The endogenous concentrations of p- and m-hydroxyphenylacetic acid in the mouse caudate nucleus were determined by a gas chromatographic or a gas chromatographic-mass spectrometric technique and the concentrations were about 30 and 11 ng g-1 respectively. The subcutaneous administration of (+)-butaclamol (1 mg kg-1), ...
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journal_title:British journal of pharmacology
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更新日期:2014-02-01 00:00:00
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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pub_type: 评论,杂志文章
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1975-06-01 00:00:00
abstract::1 The actions of 5-methoxytryptamine (5-MeOT), N,N-dimethyltryptamine (DMT), 5-hydroxy-N,N-dimethyltryptamine (bufotenine, 5-HODMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), and their interactions with 5-hydroxytryptamine (5-HT), acetylcholine, (-)-noradrenaline, and glutamate were studied by microiontophoresis...
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doi:10.1111/j.1476-5381.1974.tb09609.x
更新日期:1974-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Metformin, a small molecule, antihyperglycaemic agent, is a well-known activator of AMP-activated protein kinase (AMPK) and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. TGFβ1 is a key cytokine mediating cardiac fibrosis. Here, we investigated the effects o...
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doi:10.1111/j.1476-5381.1996.tb16063.x
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journal_title:British journal of pharmacology
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更新日期:2014-04-01 00:00:00
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journal_title:British journal of pharmacology
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abstract::Despite its long-standing reputation as a foul smelling and toxic gas that is associated with the decay of biological matter,hydrogen sulphide (H2S) has emerged as an important regulator of cardiovascular homoeostasis. H2S promotes a number of cellular signals that regulate metabolism, cardiac function and cell surviv...
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journal_title:British journal of pharmacology
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更新日期:2000-07-01 00:00:00
abstract::1. Protection against 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity by two nitric oxide-related compounds, N omega-nitro-L-arginine (L-NOARG) and L-arginine, was studied in the corpus striatum by means of two MPP+ perfusions separated by 24 h. Dopamine extracellular output after the second MPP+ (1, 5 and 10 mM)...
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更新日期:1994-03-01 00:00:00
abstract::(1) Increased oxidative stress plays a significant role in the etiology of cardiovascular disease. Lipid peroxidation, initiated in the presence of hydroxy radicals resulting in the production of malondialdehyde, directly produces oxidative stress. This study was designed to examine the direct impact of malondialdehyd...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2003-08-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1977-04-01 00:00:00