3-iodothyroacetic acid, a metabolite of thyroid hormone, induces itch and reduces threshold to noxious and to painful heat stimuli in mice

BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY 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 AND IMPLICATIONS: 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.