Diet-induced obesity alters dural CGRP release and potentiates TRPA1-mediated trigeminovascular responses

作者：Marics Balazs; Peitl Barna; Varga Angelika; Pazmandi Kitti; Bacsi Attila; Nemeth Jozsef; Szilvassy Zoltan; Jancso Gabor; Dux Maria^*

来源：Cephalalgia, 2017, 37(6): 581-591.

DOI：10.1177/0333102416654883

• Obesity
• calcitonin gene-related peptide
• sensory neuron
• laser Doppler flowmetry
• headache
• transient receptor potential ankyrin 1

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-1 beta 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.

• 出版日期2017-5