Mechanism of neuropathic pain in maxillofacial region and its association with inflammatory cytokines

颌面部神经病理性疼痛机制及其与炎性细胞因子的关系

• 批准号: 18592235
• 负责人: TANAKA Eiji
• 金额: $ 2.43万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592235/
• 关键词: Neuropathic pain; Cytokine; Pain transmission; Behavior test; Infraorbital nerve

The current literature strongly implicates a role for proinflammatory cytokines such as interleukin (IL)-1 β and tumor necrosis factor-α in the genesis or maintenance of hyperalgesia. The cytokine cascade has emerged as an important contributor to the development of persistent pain states. Importantly, the involvement of cytokines in persistent pain does not appear to be limited to peripheral sensitization. Independent of release of cytokines from the periphery site of injury, inflammatory cytokines are induced in the central nerve system (CNS). IL-1 β is a prototype proinflammatory cytokine that is highly inducible in the CNS after injury. By acting on IL-1 receptors (IL-1R) that are present on neurons and glia, IL-1 β can activate distinct intracellular signaling pathways and influence cellular function. It has been shown that IL-1 β interacts with N-methyl-D-aspartate (NMDA) receptors through activation of Src family protein tyrosine kinases, leading to enhanced NMDA receptor function. The present study directly addresses the role of proinflammatory cytokines in orofacial pain mechanisms following the chronic constriction injury (CCI) of the infraorbital nerve (IN). We demonstrate that IL-1 beta is selectively activated in astroglia in the spinal trigeminal nucleus including the subnuclei interpolaris/caudalis (Vi/Vc) transition zone and caudal subnucleus caudalis (Vc), two important regions for processing of orofacial noxious input.In conclusion, CCI of IN induced a upregulation of IL-1 beta in the spinal trigeminal nucleus including the laminated Vc and Vi/Vc. Mechanical hyperalgesia and allodynia at orofacial region developed after the chronic constriction injury of infraorbital nerve. The upregulated IL-1 beta was selectively colocalized with GFAP, a marker for astrocytes. Intrathecal infusion of IL-1ra, the naturally occurring antagonist of IL-1R, prevented the development of hyperalgesia/allodynia in orofacial region.

目前的文献强烈暗示了促炎细胞因子如白细胞介素(IL)-1 β和肿瘤坏死因子-α在痛觉过敏的发生或维持中的作用。细胞因子级联已成为持续疼痛状态发展的重要贡献者。重要的是，细胞因子在持续疼痛中的作用似乎并不局限于外周致敏。炎症细胞因子在中枢神经系统（CNS）中被诱导，不依赖于损伤外周部位细胞因子的释放。IL-1 β是一种原型促炎细胞因子，在损伤后的中枢神经系统中高度诱导。通过作用于存在于神经元和胶质细胞上的IL-1受体（IL-1R）， IL-1 β可以激活不同的细胞内信号通路并影响细胞功能。研究表明，IL-1 β通过激活Src家族蛋白酪氨酸激酶与n -甲基- d -天冬氨酸（NMDA）受体相互作用，导致NMDA受体功能增强。本研究直接探讨促炎细胞因子在眶下神经（in）慢性收缩损伤（CCI）后口面部疼痛机制中的作用。我们证明了IL-1 β在三叉神经脊髓核的星形胶质细胞中被选择性激活，包括内插/尾侧亚核（Vi/Vc）过渡区和尾侧亚核（Vc），这是处理口面部有害输入的两个重要区域。综上所述，In的CCI诱导三叉神经脊髓核包括层状Vc和Vi/Vc中IL-1 β的上调。眶下神经慢性收缩损伤后，出现了口面部机械性痛觉过敏和异常性痛。上调的IL-1 β选择性地与GFAP（星形胶质细胞的标记物）共定位。鞘内输注IL-1ra （IL-1R的天然拮抗剂）可防止口面部区域痛觉过敏/异常性痛的发生。

项目成果

IL-1 β in the trigeminal nucleus is associated with allodynia/hyperalgesia following chronic constriction infraorbital nerve injury

三叉神经核中的 IL-1 β 与慢性收缩性眶下神经损伤后的异常性疼痛/痛觉过敏相关

• 发表时间: 2007
• 作者: Suekawa;Y.;Watanabe;M.;Takahashi;K.;Myoishi;Y.;Nishi;M.;Tanaka;E.;Tanne;K
• 通讯作者: K

Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain

• DOI: 10.1523/jneurosci.0176-07.2007
• 发表时间: 2007-05-30
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Guo, Wei;Wang, Hu;Ren, Ke
• 通讯作者: Ren, Ke

Solid diet mastication reduces c-Fos expression in the rat trigeminal subnucleus caudalis following orofacial inflammation induced by CFA

固体饮食咀嚼可降低 CFA 诱导的口面部炎症后大鼠三叉神经尾亚核中 c-Fos 的表达

• 发表时间: 2006
• 期刊: Biomedical Research India (IN PRESS)
• 作者: Mika Nishi;Tatsunori Iwabe;Eiji Tanaka;Yukiko Hattori-Myoishi;Nobuhiko Kawai;Youhei Suekawa;Koji Takahashi;Mineo Watanabe;Takashi Uchida;Kazuo Tanne
• 通讯作者: Kazuo Tanne

Serotonergic neurons in the dorsal raphe nucleus are not activated by MK-801 during tooth movement

在牙齿移动过程中，MK-801 不会激活中缝背核中的血清素能神经元

• 发表时间: 2006
• 期刊: Biocnemical Research India 17/2
• 作者: Shibazaki;T. et al.
• 通讯作者: T. et al.

Solid diet mastication reduces c-Fos expression in the rat trigeminal subnucleus caudalis following orofacial inflammation induced by CEA.

在 CEA 诱导的口面部炎症后，固体饮食咀嚼可降低大鼠三叉神经尾亚核中 c-Fos 的表达。

• 发表时间: 2006
• 期刊: Biomedical Research India 17・1
• 作者: Nishi M;Iwabe T;Tanaka E;et. al.
• 通讯作者: et. al.