A FUNÇÃO DOS CANAIS DE SÓDIO NAV1.7 NA DOR NEUROPÁTICA: GENÉTICA, MECANISMOS MOLECULARES, BIOMARCADORES E PERSPECTIVAS TERAPÊUTICAS

Abstract

The deepening understanding of the molecular mechanisms underlying neuropathic pain has highlighted the importance of the sodium channel Nav1.7, encoded by the SCN9A gene, as a critical element in regulating neuronal excitability and transmitting action potentials. Nav1.7 is found in nociceptive sensory neurons, playing a vital role in conducting pain signals in the peripheral nervous system. Its activity allows the depolarization of neuronal membranes in response to painful stimuli, facilitating the rapid influx of sodium ions into the cell and generating action potentials that are sent to the brain for pain perception. Mutations in the SCN9A gene are strongly linked to various neuropathic pain conditions. Mutations that increase Nav1.7 activity, such as the p.E1113K variant, intensify the excitability of sensory neurons, leading to conditions such as primary erythromelalgia. In contrast, mutations that reduce Nav1.7 functionality, such as p.I230T, result in lower neuronal excitability, culminating in congenital insensitivity to pain. Advances in neuroimaging and molecular genetics have been fundamental in identifying biomarkers of Nav1.7 dysfunctions. These methods allow the detection of changes in pain processing within the central nervous system, facilitating the identification of specific genetic mutations that contribute to neuropathic conditions. Advanced genetic techniques, such as exome and genome sequencing, enable detailed diagnoses and personalized therapeutic approaches. Promising therapies involve specific inhibitors for Nav1.7, aiming to reduce neuronal hyperexcitability. Additionally, gene therapies, including techniques such as CRISPR-Cas9, have been explored to correct mutations in the SCN9A gene. In conclusion, scientific progress allows for precise diagnoses and personalized treatments, promoting effective management of neuropathic pain.