Nitric oxide release from trigeminal satellite glial cells is attenuated by glial modulators and glutamate

International Journal of Physiology, Pathophysiology and Pharmacology

Ujendra Kumar¹  Brian Edwin Cairns¹  Xu-Dong Dong¹  Lars Arendt-Nielsen¹  Jens Christian Laursen¹  Rishi Kumar Somvanshi¹  Parisa Gazerani¹ 

关键词: Ibudilast;    vitamin D3;    migraine;    headache;    satellite glial cells;    nitric oxide;    glutamate;    glial modulation;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

Nitric oxide (NO) is suggested to play an important role in primary headaches. It has been proposed that release of NO from satellite glial cells (SGCs) of the trigeminal ganglion (TG) could contribute to the pathogenesis of these headaches. The principal aim of this study was to investigate if the phosphodiesterase inhibitor Ibudilast (Ibu) and 1α,25-dihydroxyvitamin D₃ (Vit D₃) could interfere with NO release from trigeminal SGCs. Since glutamate is released from activated TG neurons, the ability of glutamate to alter NO release from SGCs was also investigated. To study this, we isolated SGCs from the TG of adult male Sprague-Dawley rats, provoked NO release from SGCs with forskolin (FSK; 0.1, 1, 10 μM), and examined the effect of graded concentrations of Ibu (1, 10, 100 μM), Vit D₃ (5, 50, 500 nM), and glutamate (10, 100, 1000 μM). Our results indicate that both Ibu and Vit D₃ are capable of attenuating the FSK-mediated increased NO release from SGCs after 48 hours of incubation. Lower glutamate concentrations (10 and 100 μM) significantly decreased NO release not only under basal conditions after 24 and 48 hours, but also after SGCs were stimulated with FSK for 48 hours. In conclusion, NO release from SGCs harvested from the TG can be attenuated by glial modulators and glutamate. As NO is thought to increase TG neuron excitability, the findings suggest that targeting SGCs may provide a novel therapeutic approach for management of craniofacial pain conditions such as migraine in the future.

【 授权许可】

Unknown