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Review
. 2021 Jul 12;13(7):483.
doi: 10.3390/toxins13070483.

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

Rafael González-Cano  1   2 , M Carmen Ruiz-Cantero  1   2 , Miriam Santos-Caballero  1   2 , Carlos Gómez-Navas  1 , Miguel Á Tejada  3 , Francisco R Nieto  1   2
Affiliations
Review

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

Rafael González-Cano et al. Toxins (Basel). .

Abstract

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.

Keywords: TTX; cancer pain; neuropathic pain; tetrodotoxin; voltage-gated sodium channels.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Main location of voltage specific sodium channels in the nervous system.
See this image and copyright information in PMC

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