through the chest. These symptoms are due to vasoconstriction caused by maitotoxin. Ciguatoxin lowers the threshold for opening voltage-gated sodium channels in synapses of the nervous system. Opening a sodium channel causes depolarization, which could sequentially cause paralysis, heart contraction, and changing the senses of hot and cold. Some medications such as amitriptyline may reduce some symptoms, such as fatigue and paresthesia, although benefit does not occur in every case. Mannitol Mannitol was once used for poisoning after one study reported symptom reversal. Follow-up studies in animals and case reports in humans also found benefit from mannitol. However, a randomized, double-blind clinical trial found no difference between mannitol and normal saline. Despite this its use may still be considered. Epidemiology The current estimated global incidence annually is 20,000 to 50,000 people, though a large number of cases are believed to go unreported. Due to the limited habitats of ciguatoxin-producing microorganisms, ciguatera is common only in subtropical and tropical waters, particularly the Pacific and Caribbean, and usually is associated with fish caught in tropical reef waters. Exportation of reef fish, as well as tourism, often account for cases that develop in other regions. Ciguatoxin is found in over 400 species of reef fish. Avoiding consumption of all reef fish is the only sure way to avoid exposure. Imported fish served in restaurants may contain the toxin and produce illness which often goes unexplained by physicians unfamiliar with the symptoms of a tropical toxin. Ciguatoxin can also occur in farm-raised salmon. Furthermore, species substitution, labeling a reef fish as a non-reef fish at restaurants and retail, can complicate efforts by consumers to avoid ciguatera. 20th and 21st centuries In 1994, Nobel-Prize winning novelist Saul Bellow nearly died from Ciguatera after eating red snapper on vacation in St. Martin, fictionalized in his last novel Ravelstein. In 2007, ten people in St. Louis, Missouri developed the disease after eating imported fish. In February 2008, the U.S. Food and Drug Administration (FDA) traced several outbreaks to the Flower Garden Banks National Marine Sanctuary in the northern Gulf of Mexico, near the Texas–Louisiana shoreline. The FDA advised seafood processors that ciguatera poisoning was reasonably likely to occur from eating several species of fish caught as far as from the sanctuary. From August 2010 to July 2011, there were eight outbreaks of Ciguatera fish poisoning in New York City. Outbreaks were linked to barracuda and grouper purchased