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Down-regulation of Spinal 5-HT2A and 5-HT2C Receptors Contributes to Somatic Hyperalgesia induced by Orofacial Inflammation Combined with Stress.
Neuroscience ( IF 3.3 ) Pub Date : 2020-06-01 , DOI: 10.1016/j.neuroscience.2020.05.044
Yang Xue 1 , Si-Qi Wei 1 , Pei-Xing Wang 1 , Wu-Yin Wang 1 , En-Qi Liu 2 , Richard J Traub 3 , Dong-Yuan Cao 1
Affiliation  

Patients suffering with functional somatic pain syndromes such as temporomandibular disorders (TMD) and fibromyalgia syndrome (FMS) have some similar symptoms, but the underlying cause is still unclear. The purpose of this study was to investigate whether 5-HT2A and 5-HT2C receptors in the spinal cord contribute to somatic hyperalgesia induced by orofacial inflammation combined with different modes of stress. Ovariectomized rats were injected subcutaneously with estradiol and bilateral masseter muscles were injected with complete Freund’s adjuvant followed by stress. Somatic sensitivity was assessed with thermal and mechanical stimulation. The anxiety- and depression-like behaviors were measured by immobility time, sucrose preference, elevated plus maze and open field tests. The expression of 5-HT2A and 5-HT2C receptors in the spinal cord was examined by Western blot. Orofacial inflammation combined with 11 day forced swim stress (FSS) induced persistent mechanical allodynia for 15 days and thermal hyperalgesia for 2 days. The mechanical and thermal hyperalgesia lasted for 43 days and 30 days respectively following orofacial inflammation combined with 11 day heterotypic stress. Orofacial inflammation combined with stress induced anxiety- and depression-like behaviors. The expression of 5-HT2A and 5-HT2C receptors significantly decreased in the orofacial inflammation combined with stress groups. Intrathecal injection of 5-HT2A or 5-HT2C receptor agonist reversed somatic hyperalgesia. The results suggest that down-regulation of 5-HT2A and 5-HT2C receptors in the spinal cord contributes to somatic hyperalgesia induced by orofacial inflammation combined with stress, indicating that 5-HT2A and 5-HT2C receptors may be potential targets in the treatment of TMD comorbid with FMS.



中文翻译:

脊髓5-HT 2A和5-HT 2 C受体的下调有助于口咽部炎症与压力诱导的躯体痛觉过敏。

患有功能性躯体疼痛综合征(如颞下颌疾病(TMD)和纤维肌痛综合征(FMS))的患者有一些类似的症状,但其根本原因仍不清楚。这项研究的目的是调查5-HT 2A和5-HT 2C是否脊髓中的受体介导由口腔炎症与不同压力模式结合而引起的体痛觉过敏。去卵巢的大鼠皮下注射雌二醇,双侧咬肌注射完全弗氏佐剂,然后进行应激。通过热刺激和机械刺激来评估躯体敏感性。通过不动时间,蔗糖偏爱,高架迷宫和开阔地测试来测量焦虑和抑郁样行为。5-HT 2A和5-HT 2C的表达通过蛋白质印迹检查脊髓中的受体。口腔面部炎症与11天强迫游泳压力(FSS)结合导致持续性机械性异常性疼痛持续15天,热痛觉过敏持续2天。机械和热痛觉过敏分别在口面发炎和11天异型性应激后分别持续43天和30天。口面部炎症与压力相结合会诱发焦虑和抑郁样行为。面对应激的口腔炎症中5-HT 2A和5-HT 2C受体的表达明显降低。鞘内注射5-HT 2A或5-HT 2C受体激动剂可逆转体痛觉过敏。结果表明5-HT的下调脊髓中的2A和5-HT 2C受体促进了口面炎症与压力相结合引起的躯体痛觉过敏,表明5-HT 2A和5-HT 2C受体可能是TMS与FMS合并治疗的潜在靶标。

更新日期:2020-06-23
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