González-Cano, RafaelRuiz-Cantero, M. CarmenSantos-Caballero, MiriamGómez-Navas, CarlosTejada, Miguel Á.Nieto, Francisco R.2022-09-272022-09-272021-07-12González-Cano R, Ruiz-Cantero MC, Santos-Caballero M, Gómez-Navas C, Tejada MÁ, Nieto FR. Tetrodotoxin, a Potential Drug for Neuropathic and Cancer Pain Relief? Toxins. 2021 Jul 12;13(7):483.http://hdl.handle.net/10668/4156Tetrodotoxin (TTX) is a potent neurotoxin found mainly in puffer fish and other marine and terrestrial animals. TTX blocks voltage-gated sodium channels (VGSCs) which are typically classified as TTX-sensitive or TTX-resistant channels. VGSCs play a key role in pain signaling and some TTX-sensitive VGSCs are highly expressed by adult primary sensory neurons. During pathological pain conditions, such as neuropathic pain, upregulation of some TTX-sensitive VGSCs, including the massive re-expression of the embryonic VGSC subtype NaV1.3 in adult primary sensory neurons, contribute to painful hypersensitization. In addition, people with loss-of-function mutations in the VGSC subtype NaV1.7 present congenital insensitive to pain. TTX displays a prominent analgesic effect in several models of neuropathic pain in rodents. According to this promising preclinical evidence, TTX is currently under clinical development for chemo-therapy-induced neuropathic pain and cancer-related pain. This review focuses primarily on the preclinical and clinical evidence that support a potential analgesic role for TTX in these pain states. In addition, we also analyze the main toxic effects that this neurotoxin produces when it is administered at therapeutic doses, and the therapeutic potential to alleviate neuropathic pain of other natural toxins that selectively block TTX-sensitive VGSCs.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/TetrodotoxinTTXVoltage-gated sodium channelsNeuropathic painCancer painHyperalgesiaTetrodotoxinaCanales de sodio activados por voltajeNeuralgiaDolor en cáncerMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Sensory System Agents::AnalgesicsMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Anatomy::Nervous System::Ganglia::Ganglia, Sensory::Ganglia, SpinalMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Sensation Disorders::Somatosensory Disorders::HyperalgesiaMedical Subject Headings::Diseases::NeoplasmsMedical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Pain::NeuralgiaMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Noxae::NeurotoxinsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Pain ManagementMedical Subject Headings::Chemicals and Drugs::Pharmaceutical PreparationsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Membrane Transport Modulators::Sodium Channel BlockersMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Quinazolines::TetrodotoxinMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue Proteins::Voltage-Gated Sodium ChannelsMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Up-RegulationMedical Subject Headings::Anatomy::Nervous System::Neurons::Neurons, Afferent::Sensory Receptor CellsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Fishes::TetraodontiformesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutationreview article34357955Acceso abierto10.3390/toxins130704832072-6651PMC8310002