Xue Yang, Wei Si-Qi, Wang Pei-Xing, Wang Wu-Yin, Liu En-Qi, Traub Richard J, Cao Dong-Yuan
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Research Center of Stomatology, Xi'an Jiaotong University College of Stomatology, 98 West 5th Road, Xi'an, Shaanxi 710004, PR China.
Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'an, Shaanxi 710061, PR China.
Neuroscience. 2020 Aug 1;440:196-209. doi: 10.1016/j.neuroscience.2020.05.044. Epub 2020 Jun 1.
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-HT and 5-HT 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-HT and 5-HT 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-HT and 5-HT receptors significantly decreased in the orofacial inflammation combined with stress groups. Intrathecal injection of 5-HT or 5-HT receptor agonist reversed somatic hyperalgesia. The results suggest that down-regulation of 5-HT and 5-HT receptors in the spinal cord contributes to somatic hyperalgesia induced by orofacial inflammation combined with stress, indicating that 5-HT and 5-HT receptors may be potential targets in the treatment of TMD comorbid with FMS.
患有颞下颌关节紊乱症（TMD）和纤维肌痛综合征（FMS）等功能性躯体疼痛综合征的患者有一些相似症状，但其潜在病因仍不清楚。本研究的目的是调查脊髓中的5-羟色胺（5-HT）及其受体是否参与口面部炎症联合不同应激模式诱导的躯体痛觉过敏。对去卵巢大鼠皮下注射雌二醇，双侧咬肌注射完全弗氏佐剂后施加应激。通过热刺激和机械刺激评估躯体敏感性。通过不动时间、蔗糖偏好、高架十字迷宫和旷场试验测量焦虑样和抑郁样行为。采用蛋白质免疫印迹法检测脊髓中5-HT及其受体的表达。口面部炎症联合11天强迫游泳应激（FSS）诱导持续15天的机械性异常性疼痛和持续2天的热痛觉过敏。口面部炎症联合11天异型应激后，机械性和热痛觉过敏分别持续43天和30天。口面部炎症联合应激诱导焦虑样和抑郁样行为。在口面部炎症联合应激组中，5-HT及其受体的表达显著降低。鞘内注射5-HT或5-HT受体激动剂可逆转躯体痛觉过敏。结果表明，脊髓中5-HT及其受体的下调参与了口面部炎症联合应激诱导的躯体痛觉过敏，提示5-HT及其受体可能是治疗合并FMS的TMD的潜在靶点。
