Intrathecal minocycline suppresses itch-related behavior and improves dermatitis in atopic dermatitis model mouse.
Intrathecal minocycline suppresses itch-related behavior and improves dermatitis in atopic dermatitis model mouse.
复制标题
鞘内注射米诺环素可抑制特应性皮炎模型小鼠的瘙痒相关行为并改善皮炎。
DOI：
10.1016/j.jid.2015.12.037
复制
发表时间：
2016
影响因子：
6.5
通讯作者：
Takamori K.
中科院分区：
文献类型：
--
作者：
Torigoe K;Tominaga M;Ko KC;Takahashi N;Matsuda H;Hayashi R;Ogawa H; Takamori K.
慢性和顽固性瘙痒可能由于外周和中枢神经系统中的异常神经元放电而发生。最近，已经证明脊髓胶质细胞，如小胶质细胞和星形胶质细胞，参与调节神经病理性疼痛。然而，脊髓神经胶质细胞在皮肤病如特应性皮炎（AD）的顽固性瘙痒中的作用目前尚不清楚。在NC/Nga小鼠AD样模型中，进行本研究以检查腰椎鞘内施用米诺环素（一种小胶质细胞活化抑制剂）的抗炎作用。粉尘螨体（Dfb）反复给药可诱导小鼠出现皮炎，Dfb-NC/Nga小鼠抓挠次数和脊髓Iba 1阳性（Iba 1+）小胶质细胞数量均较对照组增加。在药理学实验中，鞘内注射米诺环素剂量依赖性地减少抓挠发作，同时Dfb-NC/Nga小鼠脊髓Iba 1+小胶质细胞数量减少。鞘内注射米诺环素还改善Dfb-NC/Nga小鼠的皮炎和皮肤屏障功能。此外，口服高剂量米诺环素改善了皮炎，并显示出减少Dfb-NC/Nga小鼠中抓挠发作和脊髓Iba 1+小胶质细胞数量的趋势。因此，脊髓小胶质细胞可能是与AD相关的顽固性瘙痒的治疗靶点之一。
Chronic and intractable itch may occur due to abnormal neuronal firing in both the peripheral and central nervous systems. Recently, it has been demonstrated that spinal glial cells, such as microglia and astrocytes, are involved in modulation of neuropathic pain. However, the roles of spinal glial cells in intractable itch of skin diseases, such as atopic dermatitis (AD), are currently unknown. This study was performed to examine the antipruritic effects of lumbar intrathecal administration of minocycline, an inhibitor of microglial activation, in NC/Nga mice, AD-like model. Dermatitis was induced in mice by repeated application of Dermatophagoides farinae body (Dfb), and numbers of scratching bouts and spinal Iba1-immunoreactive (Iba1+) microglia were increased in the Dfb-NC/Nga mice compared with those in control mice. In pharmacological experiments, intrathecal minocycline dose-dependently reduced scratching bouts, concomitant with decreased number of spinal Iba1+ microglia in the Dfb-NC/Nga mice. Intrathecal minocycline also improved the dermatitis and skin barrier function in the Dfb-NC/Nga mice. Additionally, Oral administration of high-dose minocycline improved dermatitis and showed a tendency to reduce the numbers of scratching bouts and spinal Iba1+ microglia in the Dfb-NC/Nga mice. Therefore, spinal microglia may be one of the therapeutic targets for the intractable itch associated with AD.