Analgesic treatment of ciguatoxin-induced cold allodynia

Zimmermann, Katharina; Deuis, Jennifer R.; Inserra, Marco; Collins, Lindon S.; Namer, Barbara; Cabot, Peter J.; Reeh, Peter W.; Lewis, Richard J.; Vetter, Irina

doi:10.1016/j.pain.2013.06.015

Cited by 55 publications

(79 citation statements)

References 29 publications

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“…Cold allodynia e some patients describe it as a reversal of temperature sensing e is considered pathognomonic (Vetter et al, 2012;Zimmermann et al, 2013) and affects especially perioral areas, as well as the peripheral parts of the extremities. Published studies mention cold allodynia at a frequency of up to 94%, with pruritus occurring in up to 76% of ciguatera patients (Table 2).…”

Section: Long-lasting Ciguatera Symptomsmentioning

confidence: 99%

Ciguatera fish poisoning: A first epidemic in Germany highlights an increasing risk for European countries

Mattei¹,

Vetter²,

Eisenblätter³

et al. 2014

Toxicon

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a b s t r a c tToxin-producing microalgae are thriving worldwide due to coral reef destruction and global warming with major consequences on ecosystems, international trade and human health. Microalgae belonging to the family of flagellate protists, in particular dinoflagellates, secrete a variety of high-molecular-weight polyether toxins that accumulate through the marine food chain to cause disease in humans by acting as sodium channel activator toxins; ciguatera is the most frequent seafood-borne illness worldwide with 50,000 to 500,000 global incidences per annum and is usually limited to endemic areas located between 35 northern and 35 southern latitude. The rising global incidence frequency renders it a major human health problem, because no curative treatment is available yet and reliable detection assays are lacking. During the last decade ciguatera has increasingly become endemic in previously unaffected areas for two reasons: first global warming has contributed to the emergence of dinoflagellate species in subtropical and even temperate regions that previously had been constrained to tropical areas and second: in Europe globalization of fishing industry and tourism has led to a progressive increase in the number of ciguatera cases and a lack of awareness among medical personnel contributes to under-reporting. We review, through a recent ciguatera outbreak in Germany, the risk for ciguatera poisoning in Europe and highlight characteristic symptoms, current knowledge about disease pathomechanisms and treatment options.

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Section: Long-lasting Ciguatera Symptomsmentioning

confidence: 99%

Ciguatera fish poisoning: A first epidemic in Germany highlights an increasing risk for European countries

Mattei¹,

Vetter²,

Eisenblätter³

et al. 2014

Toxicon

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“…While these effects typically occur at very high concentrations, and some compounds induce cytotoxic effects on their own (Boydron-Le Garrec et al 2005), these effects may warrant further investigation in relevant to in vivo models. Recent animal studies examining a wider range of local anesthetics and anticonvulsants identified several that may also be useful at reversing signs of cold allodynia in an intraplantar mouse model of ciguatera (Zimmermann et al 2013).…”

Section: Treatment Of Ciguateramentioning

confidence: 99%

Ciguatoxin and Ciguatera

Lewis

Vetter

2016

Marine and Freshwater Toxins

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“…As of now, Na V 1.6 has already been found to be intimately involved in some clinically relevant pain conditions, one of those being ciguatoxin-induced pain and cold allodynia 200 .…”

Section: Na V 16mentioning

confidence: 98%

“…Previous studies have indicated that TTX-s Na V isoforms as well as Na V 1.8 mediate ciguatoxin-induced neuronal hyperexcitability through activating cold-specific pathways 86 . Further research indicates that when GIIIA, a Na V 1.6-selective inhibitor conotoxin, is peripherally administered together with the selective Na V 1.8 inhibitor A-803467, a significant decrease in pain behaviours such as flinching was observed in mice with ciguatoxin-induced cold allodynia 200 . The administration of GIIIA alone also significantly reduced flinching in mice, with the implication that Na V 1.6 could be the main contributor to the excitatory effects of ciguatoxin in myelinated neurons.…”

Section: Na V 16mentioning

confidence: 99%

“…In order to examine the effect of Na V 1.6, GIIIA is administered together with TIIIA, another conotoxin-derived peptide that inhibits Na V 1.1, 1.2, 1.3, and Na V 1.4 212 , but not Na V 1.6. The differential inhibitory activity of the two peptides allows for assessment of the effect of Na V 1.6 inhibition independent of Na V 1.1, Na V 1.2, and Na V 1.4 inhibition in animal models 2,133,200 . An existing peptide with the opposite action to GIIIA is the β-scorpion toxin Cn2, which functions as a potent Na V 1.6-selective activator 202 .…”

Section: Introductionmentioning

confidence: 99%

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A pharmacological and transcriptomic approach to exploring novel pain targets

Yin¹

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Ever since the discovery that mutations in the voltage-gated sodium channel 1.7 protein are responsible for human congenital insensitivity to pain, the voltage-gated sodium channel (Na V ) family of ion channels has been the subject of intense research with the hope of discovering novel analgesics. We now know that Na V 1.7 deletion in select neuronal populations yield different phenotypes, with the deletion of Na V 1.7 in all sensory neurons being successful at abolishing mechanical and heat-induced pain. However, it is rapidly becoming apparent that a number of pain syndromes are not modulated by Na V 1.7 at all, such as oxaliplatin-mediated neuropathy. It is particularly interesting to note that the loss of Na V 1.7 function is also associated with the selective inhibition of pain mediated by specific stimuli, such as that observed in burn-induced pain where Na V 1.7 gene knockout abolished thermal allodynia but did not affect mechanical allodynia. Accordingly, significant interests exist in delineating the contribution of other Na V isoforms in modality-specific pain pathways. Two other isoforms, Na V 1.6 and Na V 1.8, are now specifically implicated in some Na V 1.7-independent conditions such as oxaliplatin-induced cold allodynia. Such selective contributions of specific ion channel isoforms to pain highlight the need to discover other putative protein targets involved in mediating nociception.The aim of my work is therefore to discover selective molecular inhibitors of Na V 1.6 and Na V 1.8, to find useful cell models for peripheral nociceptors, to investigate the roles of Na V 1.6 and Na V 1.8 in an animal model of burn-induced pain, and to screen for putative new targets for analgesia in burn-related pain.Chapter 2 of this thesis describes activity-guided discovery of novel Na V 1.6 and Na V 1.8-modulting peptides from crude spider venoms. Crude venom from Poecilotheria metallica successfully reduced Na V 1.8-mediated voltage changes in HEK293-expressing cells. A new Na V 1.8-inhibitory peptide was sequenced from the venom and named Pme1a. However, Pme1a exhibited TRPV1 agonist activity and induced nocifensive behaviours, such as paw licking, after injection into the hind paws of mice, indicating the peptide was not a selective Na V 1.8 modulator and was unsuitable as a tool for Na V 1.8 investigation.iii With the unsuccessful exploration of spider venoms for new specific inhibitors, I then investigated in vitro cell models as tools to research specific nociceptor subtypes that express Na V 1.6 or Na V 1.8. In Chapter 3, I provide the first complete transcriptome of three common in vitro neuronal cell lines (SH-SY5Y, F-11, and ND7/23) to examine whether they were appropriate for investigating the functions of Na V 1.6 and Na V 1.8, and to identify if the cell lines resemble in vivo dorsal root ganglion (DRG) neuronal subclasses. The three cell lines examined all expressed proteins belonging to similar pathways and of similar proportions to native DRG neurons. However, they did not express any ce...

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Analgesic treatment of ciguatoxin-induced cold allodynia

Cited by 55 publications

References 29 publications

Ciguatera fish poisoning: A first epidemic in Germany highlights an increasing risk for European countries

Ciguatera fish poisoning: A first epidemic in Germany highlights an increasing risk for European countries

Ciguatoxin and Ciguatera

A pharmacological and transcriptomic approach to exploring novel pain targets

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