Selenium and Neurological Diseases: Focus on Peripheral Pain and TRP Channels

Abstract

Pain is a complex physiological process that includes many components. Growing evidence supports the idea that oxidative stress and Ca2+ signaling pathways participate in pain detection by neurons. The main source of endogenous reactive oxygen species (ROS) is mitochondrial dysfunction induced by membrane depolarization, which is in turn caused by Ca2+ influx into the cytosol of neurons. ROS are controlled by antioxidants, including selenium. Selenium plays an important role in the nervous system, including the brain, where it acts as a cofactor for glutathione peroxidase and is incorporated into selenoproteins involved in antioxidant defenses. It has neuroprotective effects through modulation of excessive ROS production, inflammation, and Ca2+ overload in several diseases, including inflammatory pain, hypersensitivity, allodynia, diabetic neuropathic pain, and nociceptive pain. Ca2+ entry across membranes is mediated by different channels, including transient receptor potential (TRP) channels, some of which (e.g., TRPA1, TRPM2, TRPV1, and TRPV4) can be activated by oxidative stress and have a role in the induction of peripheral pain. The results of recent studies indicate the modulator roles of selenium in peripheral pain through inhibition of TRP channels in the dorsal root ganglia of experimental animals. This review summarizes the protective role of selenium in TRP channel regulation, Ca2+ signaling, apoptosis, and mitochondrial oxidative stress in peripheral pain induction.

Therapeutic Potential of Selenium in Glioblastoma

“…The anti-gliomagenic and neuroprotective effect of Se appeared to have a role in regulation of calcium channels, in particular, transient receptor potential (TRP) cationic channels (Figure 2), including TRP melastin 2 (TRPM2) and vanilloid 1 (TRPV1) (Ataizi et al, 2019;Ertilav et al, 2019;Naziroglu et al, 2020;Akyuva et al, 2021). The involvement of TRPM2 channel FIGURE 2 | Schematic model for the potential of selenium on glioblastoma cells.…”

The P2X7 Receptor Is Involved in Diabetic Neuropathic Pain Hypersensitivity Mediated by TRPV1 in the Rat Dorsal Root Ganglion

“…Pain is a complex physiological process including many components, while chronic pain is a pathological state (Nazıroǧlu et al, 2020). DNP is one of the common chronic complications The ratio of the optical density of p-ERK1/2 to that of the internal reference.…”

“…Pain is a complex physiological process including many components, while chronic pain is a pathological state ( Nazıroǧlu et al, 2020 ). DNP is one of the common chronic complications of diabetes and an early symptom of diabetic neuropathy, which is also related to metabolic disorders, neurotrophic disorders, and autoimmune and inflammatory responses caused by hyperglycemia ( Sierra-Silvestre et al, 2018 ).…”

TRP Channels Role in Pain Associated With Neurodegenerative Diseases

“…Oxidative stress-mediated by lipid peroxidation has been observed in both neurological and peripheral pain. It has been proposed that selenium could act as neuroprotector through a mechanism that involves TRP channels inhibition, which in turn, induces modulation of ROS overproduction and Ca 2+ influx ( Nazıroğlu et al, 2020 ). Selenium is an inhibitor of TRPM2 channels, which reduces oxidative stress in the cytosol ( Zeng et al, 2012 ).…”

“…Selenium is an inhibitor of TRPM2 channels, which reduces oxidative stress in the cytosol ( Zeng et al, 2012 ). Besides TRPM2, selenium also acts as TRPA1 and TRPV1 inhibitor, suggesting that selenium could be used as a modulator of neuropathic pain through TRP channel modulation ( Nazıroğlu et al, 2020 ).…”