Zhao Ya-Juan, Liu Yang, Li Qiang, Zhao Yin-Hua, Wang Jian, Zhang Min, Chen Yong-Jin
State Key Laboratory of Military Stomatology, Department of General Dentistry & Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
Physiol Behav. 2015 Apr 1;142:57-65. doi: 10.1016/j.physbeh.2015.02.005. Epub 2015 Feb 3.
It is commonly accepted that psychological stress contributes to the development of temporomandibular joint disorders, in which chronic orofacial pain is the main symptom. However, the central mechanism underlying the development of these disorders has remained unclear. The current study was performed to determine the involvement of the glia in the trigeminal spinal subnucleus caudalis in stress-induced increases in masseter muscle hyperalgesia in rats. After being subjected to chronic restraint stress, the animals showed decreased body weight gain, behavioral changes and marked masseter allodynia. We also found that astrocytes, but not microglia, in the trigeminal subnucleus caudalis (Vc) were dramatically activated. A further analysis was undertaken to investigate the contribution of the glia; we intrathecally injected l-α-aminoadipate (astrocyte-specific inhibitor) and/or minocycline (microglia-specific inhibitor) into the stressed rats. Our results showed that l-α-aminoadipate (LAA), but not minocycline, could significantly attenuate the mechanical masseter allodynia and behavioral changes induced by restraint stress. In addition, the expression of interleukin-1β (IL-1β) and phosphorylated N-methyl-d-aspartic acid receptor 1 (p-NR1) in the Vc was significantly increased after chronic restraint stress, whereas LAA dramatically inhibited the overexpression of IL-1β and p-NR1. Taken together, these results suggest that activated astrocytes in the Vc may be one of the most important factors in the pathophysiology of masseter hyperalgesia induced by restraint stress and the following overexpression of IL-1β and excessive NMDAR phosphorylation may ultimately contribute to masseter hyperalgesia. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for the treatment of orofacial pain induced by stress.
人们普遍认为，心理压力会促使颞下颌关节紊乱症的发展，其中慢性口面部疼痛是主要症状。然而，这些紊乱症发展的中枢机制仍不清楚。当前的研究旨在确定三叉神经脊髓尾侧亚核中的神经胶质细胞是否参与应激诱导的大鼠咬肌痛觉过敏的增加。在遭受慢性束缚应激后，动物体重增加减少、行为改变且咬肌出现明显的异常性疼痛。我们还发现，三叉神经尾侧亚核（Vc）中的星形胶质细胞而非小胶质细胞被显著激活。进一步分析以研究神经胶质细胞的作用；我们向应激大鼠鞘内注射了l-α-氨基己二酸（星形胶质细胞特异性抑制剂）和/或米诺环素（小胶质细胞特异性抑制剂）。我们的结果表明，l-α-氨基己二酸（LAA）而非米诺环素能显著减轻束缚应激诱导的咬肌机械性异常性疼痛和行为改变。此外，慢性束缚应激后，Vc中白细胞介素-1β（IL-1β）和磷酸化N-甲基-D-天冬氨酸受体1（p-NR1）的表达显著增加，而LAA显著抑制IL-1β和p-NR1的过表达。综上所述，这些结果表明，Vc中被激活的星形胶质细胞可能是束缚应激诱导的咬肌痛觉过敏病理生理学中最重要的因素之一，随后IL-1β的过表达和NMDAR的过度磷酸化最终可能导致咬肌痛觉过敏。因此，抑制脊髓星形胶质细胞的激活可能是治疗应激诱导的口面部疼痛的一种新的治疗策略。
