Involvement of TRPM2 and TRPV1 channels on hyperalgesia, apoptosis and oxidative stress in rat fibromyalgia model: Protective role of selenium

Esra Yüksel,Mehmet Şahin,Mustafa Nazıroğlu,Bilal Çiğ

doi:10.1038/s41598-017-17715-1

Abstract

Fibromyalgia (FM) results in pain characterized by low selenium (Se) levels, excessive Ca2+ influx, reactive oxygen species (ROS) production, and acidic pH. TRPM2 and TRPV1 are activated by ROS and acid; nevertheless, their roles have not been elucidated in FM. Therefore, we investigated the contribution of TRPM2 and TRPV1 to pain, oxidative stress, and apoptosis in a rat model of FM and the therapeutic potential of Se. Thirty-six rats were divided into four groups: control, Se, FM, and FM + Se. The Se treatment reduced the FM-induced increase in TRPM2 and TRPV1 currents, pain intensity, intracellular free Ca2+, ROS, and mitochondrial membrane depolarization in the sciatic (SciN) and dorsal root ganglion (DRGN) neurons. Furthermore, Se treatment attenuated the FM-induced decrease in cell viability in the DRGN and SciN, glutathione peroxidase, and reduced glutathione and α-tocopherol values in the DRGN, SciN, brain, muscle, and plasma; however, lipid peroxidation levels were decreased. Se also attenuated PARP1, caspase 3, and 9 expressions in the SciN, DRGN, and muscle. In conclusion, Se treatment decreased the FM-induced increase in hyperalgesia, ROS, apoptosis, and Ca2+ entry through TRPM2 and TRPV1 in the SciN and DRGN. Our findings may be relevant to the elucidation and treatment of FM.

Highlights

Fibromyalgia (FM) is a common chronic pain syndrome affecting up to 4 million adults in the United States, about 2% of the adult population[1]
The results of the current study indicated that Se treatment might decrease FM-induced pain intensity, [Ca2+]i accumulation, mitochondrial reactive oxygen species (ROS), and apoptosis levels in the dorsal root ganglion (DRGN) and sciatic nerve neuron (SciN) by blocking the TRPM2 and
The blockage of TRPM2 and TRPV1 generally results in antinociceptive effects in animal models; the roles of TRPM2 and TRPV1 in maintaining acid- and oxidative stress-induced chronic hyperalgesia in animal models have not been elucidated

Summary

Introduction

Fibromyalgia (FM) is a common chronic pain syndrome affecting up to 4 million adults in the United States, about 2% of the adult population[1] Various factors such as oxidative stress and calcium ion (Ca2+) influx overload play major roles in the etiology of FM. Oxidative stress and the acid-dependent activation of the TRPM2 and TRPV1 channels may be involved in the etiology of FM in the FM rat model. Se may modulate Ca2+ influx via the TRPM2 and TRPV1 channels; it may affect oxidative stress and apoptosis in the DRGN and SciN of rats with FM. The aim of the current study is to determine the molecular mechanism of the effect of Se on apoptosis, oxidative stress, and Ca2+ entry through TRPV1 and TRPM2 regulation in the DRGN and SciN after FM induction

Objectives

Methods

Results

Conclusion