Laurino Annunziatina, De Siena Gaetano, Resta Francesco, Masi Alessio, Musilli Claudia, Zucchi Riccardo, Raimondi Laura
Department of NEUROFARBA, Section of Pharmacology, University of Florence, Florence, Italy.
Br J Pharmacol. 2015 Apr;172(7):1859-68. doi: 10.1111/bph.13032. Epub 2015 Jan 23.
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.
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.
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.
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.
瘙痒与对伤害性刺激的敏感性增加有关。我们研究了3 - 碘甲状腺乙酸（TA1）是否通过释放组胺诱导瘙痒，并增加对有害和疼痛热刺激的敏感性。
皮下注射TA1（0.4、1.32和4μg·kg⁻¹）后评估瘙痒情况。分别在腹腔注射TA1（0.4、1.32和4μg·kg⁻¹）15分钟后，通过升温热板（从45.5℃升至49.5℃）或热板（51.5℃）试验评估小鼠对有害热刺激（NHT）和疼痛热刺激的阈值。在用吡苄明预处理的小鼠中重复进行瘙痒、NHT和疼痛阈值评估。在注射生理盐水或TA1（1.32、4和11μg·kg⁻¹；皮下和腹腔注射）后，还测量了HDC(+/+)和HDC(-/-)小鼠的瘙痒和NHT。在从CD1小鼠分离的背根神经节（DRG）中，于腹腔注射后15分钟通过蛋白质免疫印迹法测定pERK1/2水平，注射的物质分别为：生理盐水、生理盐水加有害热刺激（46.5℃）、TA1（0.1、0.4、1.32、4μg·kg⁻¹）或TA1 1.32μg·kg⁻¹加有害热刺激。
0.4和1.32μg·kg⁻¹的TA1诱导瘙痒并降低NHT；吡苄明预处理可预防这两种效应。4μg·kg⁻¹（腹腔注射）的TA1降低疼痛阈值，但不诱导瘙痒或改变NHT。在HDC(-/-)小鼠中，TA1未能诱导瘙痒和降低NHT。在DRG中，有害热刺激以及0.1、0.4和1.32μg·kg⁻¹（腹腔注射）的TA1可显著增加pERK1/2水平。
TA1水平升高诱导瘙痒并增强对有害热刺激的敏感性，表明TA1可能是甲状腺疾病中瘙痒的一个潜在原因。
