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Centipede bites are usually characterized by mildly to moderately painful encounters with humans, however, they are relatively infrequent. The vast majority of centipede envenomations do not cause severe symptoms and only in very rare cases more serious symptoms such as myocardial ischemia and infarction, hematuria, hemoglobinuria, rhabdomyolysis, hemorrhage, pruritus, eosinophilic cellulitis, as well as anaphylaxis are observed. More prevalent are symptoms including pain, paresthesia, lethargy, localized necrosis, headache, dizziness and nausea. The numerous symptoms and complications elicited by these envenomations indicate that centipede venom possesses an arsenal of chemical components with functional diversity. Centipede venom is a rich and complex natural source of bioactive proteins, peptides and other small molecules that aid in predation or defense. The venom can induce myotoxic, cardiotoxic, neurotoxic and other toxic effects. The constituents target different cellular processes and pathways which in turn trigger a cascade of physiological reactions in the victim. The venom components are potent and selective on peripheral targets; thus, they are valuable in studying the molecular basis of these envenomation symptoms and complications. This review highlights the clinical importance of centipede envenomation and the recent discoveries on the underlying molecular mechanisms of the resulting symptoms which is crucial in therapy.Centipede bites can inflict a range of symptoms on musculoskeletal, blood, nervous and cardiovascular systems.About 0.43% of all centipede species are potentially clinically important, in which Scolopendra species are the majority.Molecular diversity of centipede venom and numerosity of the induced symptoms suggest its functional diversity.The constituents of centipede venom can act on multi-functional targets thereby affecting different physiological systems.Understanding mechanism of action of centipede venom components is vital in elucidating their contribution to bite symptoms.