title: Nitric oxide release from trigeminal satellite glial cells is attenuated by glial modulators and glutamate.
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.
authors.affiliation: 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.
authors.forename: Jens Christian
authors.initials: JC
authors.lastname: Laursen
authors.affiliation: 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.
authors.forename: Brian Edwin
authors.initials: BE
authors.lastname: Cairns
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia 2405 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Ujendra
authors.initials: U
authors.lastname: Kumar
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia 2405 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Rishi Kumar
authors.initials: RK
authors.lastname: Somvanshi
authors.affiliation: 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.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Dong
authors.affiliation: 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.
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.affiliation: 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.
authors.forename: Parisa
authors.initials: P
authors.lastname: Gazerani
keywords: Ibudilast; glial modulation; glutamate; headache; migraine; nitric oxide; satellite glial cells; vitamin D3