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REVIEW article

Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1472771
This article is part of the Research Topic Pharmacological Advances to Treat Pathological Pain View all articles

TLR4 induced TRPM2 mediated neuropathic pain

Provisionally accepted
Venkata Kiran Kumar K. Mandlem Venkata Kiran Kumar K. Mandlem 1Ana Rivera Ana Rivera 1Zaina Khan Zaina Khan 1,2Sohel H. Quazi Sohel H. Quazi 1,3Farah Deba Farah Deba 1*
  • 1 University of Texas at Tyler, Tyler, United States
  • 2 The University of Texas at Dallas, Richardson, Texas, United States
  • 3 Texas College, Tyler, Texas, United States

The final, formatted version of the article will be published soon.

    Ion channels play an important role in mediating pain through signal transduction, regulation, and control of responses, particularly in neuropathic pain. Transient receptor potential channel superfamily plays an important role in cation permeability and cellular signaling. Transient receptor potential channel Melastatin 2 (TRPM2) subfamily regulates Ca 2+ concentration in response to various chemicals and signals from the surrounding environment. TRPM2 has a role in several physiological functions such as cellular osmosis, temperature sensing, cellular proliferation, as well as the manifestation of many disease processes such as pain process, cancer, apoptosis, endothelial dysfunction, angiogenesis, renal and lung fibrosis, and cerebral ischemic stroke. Toll-like Receptor 4 (TLR4) is a critical initiator of the immune response to inflammatory stimuli, particularly those triggered by Lipopolysaccharide (LPS). It activates downstream pathways leading to the production of oxidative molecules and inflammatory cytokines, which are modulated by basal and store-operated calcium ion signaling. The cytokine production and release cause an imbalance of antioxidant enzymes and redox potential in the Endoplasmic Reticulum and mitochondria due to oxidative stress, which results from TLR-4 activation and consequently induces the production of inflammatory cytokines in neuronal cells, exacerbating the pain process.Very few studies have reported the role of TRPM2 and its association with Toll-like receptors in the context of neuropathic pain. However, the molecular mechanism underlying the interaction between TRPM2 and TLR-4 and the quantum of impact in acute and chronic neuropathic pain remains unclear. Understanding the link between TLR-4 and TRPM2 will provide more insights into pain regulation mechanisms for the development of new therapeutic molecules to address neuropathic pain.

    Keywords: Inflammation, neuropathic pain, Reactive Oxygen Species, Lipopolysac Reactive Oxygen Species (ROS), Nicotinamide Adenine Dinucleotide phosphate [NADPH] oxidase (NOX).

    Received: 30 Jul 2024; Accepted: 02 Sep 2024.

    Copyright: © 2024 Mandlem, Rivera, Khan, Quazi and Deba. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Farah Deba, University of Texas at Tyler, Tyler, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.