title: 3-iodothyroacetic acid, a metabolite of thyroid hormone, induces itch and reduces threshold to noxious and to painful heat stimuli in mice.
abstract: OBJECTIVE
  Itch is associated with increased sensitization to nociceptive stimuli. We investigated whether 3-iodothyroacetic acid (TA1), by releasing histamine, induces itch and increases sensitization to noxious and painful heat stimuli.
  
  
  METHODS
  Itch was evaluated after s.c. administration of TA1 (0.4, 1.32 and 4 μg·kg(-1) ). Mice threshold to noxious (NHT) and to painful heat stimuli were evaluated by the increasing-temperature hot plate (from 45.5 to 49.5°C) or by the hot plate (51.5°C) test, respectively, 15 min after i.p. injection of TA1 (0.4, 1.32 and 4 μg·kg(-1) ). Itch, NHT and pain threshold evaluation were repeated in mice pretreated with pyrilamine. Itch and NHT were also measured in HDC(+/+) and HDC(-/-) following injection of saline or TA1 (1.32, 4 and 11 μg·kg(-1) ; s.c. and i.p.). pERK1/2 levels were determined by Western blot in dorsal root ganglia (DRG) isolated from CD1 mice 15 min after they received (i.p.): saline, saline and noxious heat stimulus (46.5°C), TA1 (0.1, 0.4, 1.32, 4 μg·kg(-1) ) or TA1 1.32 μg·kg(-1) and noxious heat stimulus.
  
  
  RESULTS
  TA1 0.4 and 1.32 μg·kg(-1) induced itch and reduced NHT; pyrilamine pretreatment prevented both of these effects. TA1 4 μg·kg(-1) (i.p.) reduced pain threshold without inducing itch or modifying NHT. In HDC(-/-) mice, TA1 failed to induce itch and to reduce NHT. In DRG, pERK1/2 levels were significantly increased by noxious heat stimuli and by TA1 0.1, 0.4 and 1.32 μg·kg(-1) ; i.p.
  
  
  CONCLUSIONS
  Increased TA1 levels induce itch and an enhanced sensitivity to noxious heat stimuli suggesting that TA1 might represent a potential cause of itch in thyroid diseases.
authors.affiliation: Department of NEUROFARBA, Section of Pharmacology, University of Florence, Florence, Italy.
authors.forename: Annunziatina
authors.initials: A
authors.lastname: Laurino
authors.forename: Gaetano
authors.initials: G
authors.lastname: De Siena
authors.forename: Francesco
authors.initials: F
authors.lastname: Resta
authors.forename: Alessio
authors.initials: A
authors.lastname: Masi
authors.forename: Claudia
authors.initials: C
authors.lastname: Musilli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zucchi
authors.forename: Laura
authors.initials: L
authors.lastname: Raimondi
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000235:genetics; D006358:Hot Temperature / Q000009:adverse effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010146:Pain / Q000209:etiology; D017288:Pain Threshold / Q000187:drug effects*; D011537:Pruritus / Q000139:chemically induced* / Q000378:metabolism; D011738:Pyrilamine / Q000494:pharmacology; D017208:Rats, Wistar; D050916:TRPV Cation Channels / Q000502:physiology; D013963:Thyroid Hormones / Q000378:metabolism; D013970:Thyronines / Q000494:pharmacology*
chemical_list: C000597002:3-iodothyroacetic acid; D006634:Histamine H1 Antagonists; D050916:TRPV Cation Channels; D013963:Thyroid Hormones; D013970:Thyronines; C493922:Trpv1 protein, rat; D006640:Histidine Decarboxylase; D011738:Pyrilamine