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Neuropathic Pain: Delving Into the Oxidative Origin and the Possible Implication of Transient Receptor Potential Channels


Neuropathic Pain: Delving Into the Oxidative Origin and the Possible Implication of Transient Receptor Potential Channels

Cristina Carrasco et al. Front Physiol.


Currently, neuropathic pain is an underestimated socioeconomic health problem affecting millions of people worldwide, which incidence may increase in the next years due to chronification of several diseases, such as cancer and diabetes. Growing evidence links neuropathic pain present in several disorders [i.e., spinal cord injury (SCI), cancer, diabetes and alcoholism] to central sensitization, as a global result of mitochondrial dysfunction induced by oxidative and nitrosative stress. Additionally, inflammatory signals and the overload in intracellular calcium ion could be also implicated in this complex network that has not yet been elucidated. Recently, calcium channels namely transient receptor potential (TRP) superfamily, including members of the subfamilies A (TRAP1), M (TRPM2 and 7), and V (TRPV1 and 4), have demonstrated to play a role in the nociception mediated by sensory neurons. Therefore, as neuropathic pain could be a consequence of the imbalance between reactive oxygen species and endogen antioxidants, antioxidant supplementation may be a treatment option. This kind of therapy would exert its beneficial action through antioxidant and immunoregulatory functions, optimizing mitochondrial function and even increasing the biogenesis of this vital organelle; on balance, antioxidant supplementation would improve the patient's quality of life. This review seeks to deepen on current knowledge about neuropathic pain, summarizing clinical conditions and probable causes, the relationship existing between oxidative stress, mitochondrial dysfunction and TRP channels activation, and scientific evidence related to antioxidant supplementation.

Keywords: TRP channels; antioxidants; inflammation; mitochondrial dysfunction; neuropathic pain; oxidative stress.


Figure 1
Figure 1
Summary of harmful effects of nitro-oxidative stress on neuronal cells in neuropathic pain (CAT, catalase; GPx, glutathione peroxidase; GSH, glutathione; IL-1/6, interleukin 1/6; ROS/RNS, reactive oxygen species/reactive nitrogen species; SOD, superoxide dismutase; TNF-α, tumor necrosis factor-α; TRP, transient receptor potential; TRPA1, transient receptor potential ankyrin 1; TRPM2, transient receptor potential melastatin 2; TRPV1/4, transient receptor potential vanilloid 1/4).
Figure 2
Figure 2
Relation between nitro-oxidative stress, mitochondrial dysfunction and apoptosis in chemotherapy-induced peripheral neuropathy (ATP, adenosine triphosphate; ETC, electronic transport channel; mtDNA, mitochondrial DNA; mPTP, mitochondrial permeability transition pore; ROS/RNS, reactive oxygen species/reactive nitrogen species).

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