Diet-induced obesity alters dural CGRP release and potentiates TRPA1-mediated trigeminovascular responses.
Background Clinical studies suggest a link between obesity and the primary headache disorder migraine. In our study we aimed to reveal the effect of obesity on meningeal nociceptor function in rats receiving a high-fat, high-sucrose diet. Methods Transient receptor potential ankyrin 1 (TRPA1) receptor activation-induced changes in meningeal blood flow, release of calcitonin gene-related peptide (CGRP) from trigeminal afferents and TRPA1 protein expression in the trigeminal ganglia were measured in control and obese rats. Metabolic parameters of the animals were assessed by measuring glucose and insulin homeostasis as well as plasma cytokine concentrations. Results The present experiments revealed an enhanced basal and TRPA1 receptor agonist-induced CGRP release from meningeal afferents of obese insulin-resistant rats and an attenuated CGRP release to potassium chloride. Obesity was also associated with an augmented vasodilatation in meningeal arteries after dural application of the TRPA1 agonist acrolein, a reduction in TRPA1 protein expression in the trigeminal ganglia and elevations in circulating proinflammatory cytokines IL-1β and IL-6 in addition to increased fasting blood glucose and insulin concentrations. Conclusions Our results suggest trigeminal sensitisation as a mechanism for enhanced headache susceptibility in obese individuals after chemical exposure of trigeminal nociceptors.
1 Department of Pharmacology and Pharmacotherapy, University of Debrecen, Debrecen, Hungary.
Balázs
B
Marics
1 Department of Pharmacology and Pharmacotherapy, University of Debrecen, Debrecen, Hungary.
Barna
B
Peitl
2 Department of Physiology, University of Debrecen, Debrecen, Hungary.
Angelika
A
Varga
3 Department of Immunology, University of Debrecen, Debrecen, Hungary.
Kitti
K
Pázmándi
3 Department of Immunology, University of Debrecen, Debrecen, Hungary.
Attila
A
Bácsi
1 Department of Pharmacology and Pharmacotherapy, University of Debrecen, Debrecen, Hungary.
József
J
Németh
1 Department of Pharmacology and Pharmacotherapy, University of Debrecen, Debrecen, Hungary.
Zoltán
Z
Szilvássy
4 Department of Physiology, University of Szeged, Szeged, Hungary.
Gábor
G
Jancsó
4 Department of Physiology, University of Szeged, Szeged, Hungary.
Mária
M
Dux
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D019422:Dietary Sucrose / Q000009:adverse effects*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074025:TRPA1 Cation Channel / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000378:metabolism*; D014653:Vascular Headaches / Q000209:etiology / Q000378:metabolism*
D001786:Blood Glucose; D019422:Dietary Sucrose; D018836:Inflammation Mediators; D000074025:TRPA1 Cation Channel; C480976:Trpa1 protein, rat; D015740:Calcitonin Gene-Related Peptide
Obesity; calcitonin gene-related peptide; headache; laser Doppler flowmetry; sensory neuron; transient receptor potential ankyrin 1