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Nair, Nitasha

University of British Columbia

The nociceptive signal from the affected craniofacial region is transmitted by the peripheral branches of the trigeminal nerve to the trigeminal ganglion and these signals are further transmitted to the higher orders of the brain leading to an enhanced sensitivity to pain in conditions like migraine headache. The trigeminal ganglion is comprised of cell bodies of trigeminal sensory neurons and surrounding these neurons are the satellite glial cells (SGCs). There is a minute gap between the cell membrane of these glial cells and trigeminal ganglion neurons which allows SGCs to regulate levels of neurotransmitters and neuropeptides in the intraganglionic space. The SGCs also express transporters for the uptake of neurotransmitters (glutamate, GABA). SGCs have glutamate-glutamine shuttles that are responsible for converting the excess glutamate to glutamine with the help of the enzyme glutamine synthetase (GS), which is the marker of SGCs. Previous studies have shown that SGCs release glutamate when they are depolarized with potassium chloride (KCl). Somatostatin (SST) is an inhibitory neuropeptide, and the action of SST is regulated by five somatostatin receptor subtypes (SSTR1-5). Previous work suggests that SSTR2 is expressed by trigeminal SGCs. The expression of other SSTRs on SGCs and the effect of activation of SSTRs to regulate glutamate release from these cells have not yet been investigated. In the current study, immunocytochemistry was employed to show that SST and all subtypes of SSTRs were expressed by SGCs. SSTR5 (19 ± 1%) was the most abundant while SSTR2 (13 ± 0.1%) was the least expressed SSTR subtype in these glial cells. The expression of SSTR2-5 (excluding SSTR1) was further confirmed by western blot analysis. Cultured SGCs were pretreated with varying concentrations of SST (25nM-10μM) and depolarized with KCl to trigger glutamate release. SST attenuated the release of glutamate from SGCs after the cells were subjected to KCl-mediated depolarization. This study confirmed the expression of all SSTR subtypes on SGCs and showed that SST could attenuate the release of glutamate from SGCs after they were depolarized with KCl. Therefore, targeting these cells could be useful to alleviate orofacial pain in conditions like migraine headache.

Text

2024-09-05

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89177

Pharmaceutical Sciences

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/