Critical role for spinal caspase-1 in neuropathic pain development through its distinct regulation of cytokines

脊髓 caspase-1 通过其对细胞因子的独特调节在神经性疼痛发展中发挥关键作用

• 批准号: 22790195
• 负责人: MIYOSHI Kan
• 金额: $ 2.25万
• 依托单位: Hyogo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790195/
• 关键词: Caspase-1; IL-18; microglia; neuropathic pain; spinal cord; astrocytes; glial interaction; caspase-1; astrocyte; TLR4; IL-1β

SNL induced an increase in the expression of IL-18 and caspase-1 in microglia, in the spinal dorsal horn. Intrathecal injection of the TLR4 agonist, LPS, produced upregulation of Iba1, caspase-1, and IL-18 expression, which was prevented by a p38 MAPK inhibitor. Both anti-IL-18 antibody and caspase-1 inhibitors alleviated SNL-induced tactile allodynia. Conversely, intrathecal injection of IL-18 produced both tactile allodynia. IL-18-deficient mice or caspase-1-deficient mice did not develop tactile allodynia after SNL. Thus, blocking IL-18 signaling in glial cells might provide a fruitful strategy for treating neuropathic pain.

SNL 诱导脊髓背角小胶质细胞中 IL-18 和 caspase-1 的表达增加。鞘内注射 TLR4 激动剂 LPS 会导致 Iba1、caspase-1 和 IL-18 表达上调，而 p38 MAPK 抑制剂可以阻止这种表达。抗 IL-18 抗体和 caspase-1 抑制剂均可减轻 SNL 诱导的触觉异常性疼痛。相反，鞘内注射 IL-18 会产生触觉异常性疼痛。 IL-18 缺陷型小鼠或 caspase-1 缺陷型小鼠在 SNL 后不会出现触觉异常性疼痛。因此，阻断神经胶质细胞中的 IL-18 信号传导可能为治疗神经性疼痛提供富有成效的策略。

项目成果

Critical role for spinal IL-18/caspase-1 interaction in neuropathic pain development through its distinct regulation of interleukins

脊髓 IL-18/caspase-1 相互作用通过其对白细胞介素的独特调节在神经性疼痛发展中发挥关键作用

• 发表时间: 2010
• 作者: Miyoshi K;Noguchi K.
• 通讯作者: Noguchi K.

Spinal 5-HT(3) receptor activation induces behavioral hypersensitivity via a neuronal-glial-neuronal signaling cascade.

• DOI: 10.1523/jneurosci.1564-11.2011
• 发表时间: 2011-09-07
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Gu M;Miyoshi K;Dubner R;Guo W;Zou S;Ren K;Noguchi K;Wei F
• 通讯作者: Wei F

Critical role for spinal IL-18/caspase-1 interaction in neuropathic pain development through its distinct regulation of interleukins.

脊髓 IL-18/caspase-1 相互作用通过其对白细胞介素的独特调节在神经性疼痛发展中发挥关键作用。

• 发表时间: 2010
• 作者: Miyoshi;K.;et.al.
• 通讯作者: et.al.

Re-evaluation of the phenotypic changes in L4 dorsal root ganglion neurons after L5 spinal nerve ligation

• DOI: 10.1016/j.pain.2011.09.009
• 发表时间: 2012-01-01
• 期刊: PAIN
• 影响因子: 7.4
• 作者: Fukuoka, Tetsuo;Yamanaka, Hiroki;Noguchi, Koichi
• 通讯作者: Noguchi, Koichi

Sleep disturbances in a neuropathic pain-like condition in the mouse are associated with altered GABAergic transmission in the cingulate cortex

• DOI: 10.1016/j.pain.2011.02.016
• 发表时间: 2011-06-01
• 期刊: PAIN
• 影响因子: 7.4
• 作者: Narita, Minoru;Niikura, Keiichi;Suzuki, Tsutomu
• 通讯作者: Suzuki, Tsutomu