title: Decreased pain threshold and enhanced synaptic transmission in the anterior cingulate cortex of experimental hypothyroidism mice.
abstract: BACKGROUND
  Thyroid hormones are essential for the maturation and functions of the central nervous system. Pain sensitivity is related to the thyroid status. However, information on how thyroid hormones affect pain processing and synaptic transmission in the anterior cingulate cortex (ACC) is limited. Nociceptive threshold and synaptic transmission in the ACC were detected in the experimental hypothyroidism (HT) mice.
  
  
  RESULTS
  HT was induced by methimazole and potassium perchlorate in distilled drinking water for 4 weeks. The threshold of pain perception to hot insults, but not mechanical ones, decreased in hypothyroid mice. After treatment with tri-iodothyronine (T3) or thyroxine (T4) for 2 weeks, thermal pain threshold recovered. Electrophysiological recordings revealed enhanced glutamatergic synaptic transmission and reduced GABAergic synaptic transmission in the ACC. Supplementation with T3 or T4 significantly rescued this synaptic transmission imbalance. In the same model, HT caused the up-regulation of the GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and NR2B-containing N-methyl-D-aspartate receptors, but it down-regulated γ-aminobutyric acid A receptors in the ACC. Supplementation with T3 or T4 notably recovered the levels of above proteins.
  
  
  CONCLUSIONS
  These results suggest that HT promotes hypersensitivity to noxious thermal, and that supplementation with T3 or T4 rescues the imbalance between excitatory and inhibitory transmission in the ACC.
authors.forename: Jun
authors.initials: J
authors.lastname: Yi
authors.forename: Jian-yong
authors.initials: JY
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Xijing Hospital; The Fourth Military Medical University, Xi'an 710032, China. yangtian@fmmu.edu.cn.
authors.forename: Zhi-fu
authors.initials: ZF
authors.lastname: Yang
authors.forename: Ke-feng
authors.initials: KF
authors.lastname: Dou
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology*; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D007037:Hypothyroidism / Q000097:blood / Q000150:complications / Q000209:etiology / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D008713:Methimazole / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010472:Perchlorates / Q000633:toxicity; D017680:Potassium Compounds / Q000633:toxicity; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D008713:Methimazole; D010472:Perchlorates; D017680:Potassium Compounds; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D013974:Thyroxine; D014284:Triiodothyronine; C121001:NR2B NMDA receptor; C009006:potassium perchlorate