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Review

Tetrodotoxin, a Potential Drug for Neuropathic and Cancer Pain Relief?

1
Department of Pharmacology, and Neurosciences Institute (Biomedical Research Center), University of Granada, 18016 Granada, Spain
2
Biosanitary Research Institute ibs.GRANADA, 18012 Granada, Spain
3
INCLIVA Health Research Institute, 46010 Valencia, Spain
*
Author to whom correspondence should be addressed.
Toxins 2021, 13(7), 483; https://doi.org/10.3390/toxins13070483
Received: 19 June 2021 / Revised: 8 July 2021 / Accepted: 9 July 2021 / Published: 12 July 2021
(This article belongs to the Special Issue Tetrodotoxin (TTX) as a Therapeutic Agent)
Tetrodotoxin (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. View Full-Text
Keywords: tetrodotoxin; TTX; voltage-gated sodium channels; neuropathic pain; cancer pain tetrodotoxin; TTX; voltage-gated sodium channels; neuropathic pain; cancer pain
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MDPI and ACS Style

González-Cano, R.; Ruiz-Cantero, M.C.; Santos-Caballero, M.; Gómez-Navas, C.; Tejada, M.Á.; Nieto, F.R. Tetrodotoxin, a Potential Drug for Neuropathic and Cancer Pain Relief? Toxins 2021, 13, 483. https://doi.org/10.3390/toxins13070483

AMA Style

González-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; 13(7):483. https://doi.org/10.3390/toxins13070483

Chicago/Turabian Style

González-Cano, Rafael, M. Carmen Ruiz-Cantero, Miriam Santos-Caballero, Carlos Gómez-Navas, Miguel Á. Tejada, and Francisco R. Nieto. 2021. "Tetrodotoxin, a Potential Drug for Neuropathic and Cancer Pain Relief?" Toxins 13, no. 7: 483. https://doi.org/10.3390/toxins13070483

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