miRNAs: Important Targets for Oral Cancer Pain Research

Pain is a symptom shared by an incredible number of diseases. It is also one of the primary conditions that prompt individuals to seek medical treatment. Head and neck squamous cell carcinoma (HNSCC) corresponds to a heterogeneous disease that may arise from many distinct structures of a large, highly complex, and intricate region. HNSCC affects a great number of patients worldwide and is directly associated with chronic pain, which is especially prominent during the advanced stages of oral squamous cell carcinoma (OSCC), an anatomical and clinical subtype that corresponds to the great majority oral cancers. Although the cellular and molecular bases of oral cancer pain have not been fully established yet, the results of recent studies suggest that different epigenetic mechanisms may contribute to this process. For instance, there is strong scientific evidence that microRNAs (miRNAs), small RNA molecules that do not encode proteins, might act by regulating the mechanisms underlying cancer-related pain. Among the miRNAs that could possibly interfere in pain-signaling pathways, miR-125b, miR-181, and miR-339 emerge as some of the most promising candidates. In fact, such molecules apparently contribute to inflammatory pain. Moreover, these molecules possibly influence the activity of endogenous pain control systems (e.g., opioidergic and serotonergic systems), which could ultimately result in peripheral and central sensitization, central nervous system (CNS) phenomena innately associated with chronic pain. This review paper focuses on the current scientific knowledge regarding the involvement of miRNAs in cancer pain, with special attention dedicated to OSCC-related pain.

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