title: Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling.
abstract: Ciguatoxins are sodium channel activator toxins that cause ciguatera, the most common form of ichthyosarcotoxism, which presents with peripheral sensory disturbances, including the pathognomonic symptom of cold allodynia which is characterized by intense stabbing and burning pain in response to mild cooling. We show that intraplantar injection of P-CTX-1 elicits cold allodynia in mice by targeting specific unmyelinated and myelinated primary sensory neurons. These include both tetrodotoxin-resistant, TRPA1-expressing peptidergic C-fibres and tetrodotoxin-sensitive A-fibres. P-CTX-1 does not directly open heterologously expressed TRPA1, but when co-expressed with Na(v) channels, sodium channel activation by P-CTX-1 is sufficient to drive TRPA1-dependent calcium influx that is responsible for the development of cold allodynia, as evidenced by a large reduction of excitatory effect of P-CTX-1 on TRPA1-deficient nociceptive C-fibres and of ciguatoxin-induced cold allodynia in TRPA1-null mutant mice. Functional MRI studies revealed that ciguatoxin-induced cold allodynia enhanced the BOLD (Blood Oxygenation Level Dependent) signal, an effect that was blunted in TRPA1-deficient mice, confirming an important role for TRPA1 in the pathogenesis of cold allodynia.
authors: Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia.
authors: Irina
authors: I
authors: Vetter
authors: Filip
authors: F
authors: Touska
authors: Andreas
authors: A
authors: Hess
authors: Rachel
authors: R
authors: Hinsbey
authors: Simon
authors: S
authors: Sattler
authors: Angelika
authors: A
authors: Lampert
authors: Marina
authors: M
authors: Sergejeva
authors: Anastasia
authors: A
authors: Sharov
authors: Lindon S
authors: LS
authors: Collins
authors: Mirjam
authors: M
authors: Eberhardt
authors: Matthias
authors: M
authors: Engel
authors: Peter J
authors: PJ
authors: Cabot
authors: John N
authors: JN
authors: Wood
authors: Viktorie
authors: V
authors: Vlachová
authors: Peter W
authors: PW
authors: Reeh
authors: Richard J
authors: RJ
authors: Lewis
authors: Katharina
authors: K
authors: Zimmermann
mesh_terms: D000818:Animals; D002922:Ciguatoxins / Q000633:toxicity*; D003080:Cold Temperature; D006930:Hyperalgesia / Q000139:chemically induced; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000187:drug effects / Q000235:genetics
chemical_list: D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D002922:Ciguatoxins