IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2013;5(4):228-238

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

Jens Christian Laursen, Brian Edwin Cairns, Ujendra Kumar, Rishi Kumar Somvanshi, Xu-Dong Dong, Lars Arendt-Nielsen, Parisa
Gazerani

Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Fredrik
Bajers Vej 7D3, Aalborg Ø, DK-9220, Denmark; Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405
Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3; College of Stomatology, Tianjin Medical University, Tianjin 300071, China

Received October 10, 2013; Accepted November 30, 2013; Epub December 15, 2013; Published December 30, 2013

Abstract: 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. (IJPPP1310001).

Keywords: Ibudilast, vitamin D3, migraine, headache, satellite glial cells, nitric oxide, glutamate, glial modulation

Address correspondence to: Dr. Parisa Gazerani, Center for Sensory-Motor Interaction, Department of Health Science and
Technology, Faculty of Medicine, Aalborg University, Fredrik Bajers Vej 7D3, DK-9220, Aalborg East, Denmark. Tel: +45 9940 2412; Fax:
+45 9815 4008; E-mail: gazerani@hst.aau.dk