Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226019, China.
Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.
Neurosci Bull. 2018 Feb;34(1):54-63. doi: 10.1007/s12264-017-0128-z. Epub 2017 Apr 11.
Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3 mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3 mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.
最近的研究表明，背根神经节中的趋化因子受体 CXCR3 及其配体 CXCL10 介导实验性变应性接触性皮炎 (ACD) 中的瘙痒。脊髓中的 CXCR3 也有助于神经性疼痛的维持。然而，脊髓 CXCR3 是否参与急性或慢性瘙痒仍不清楚。在这里，我们报告 Cxcr3 小鼠在急性瘙痒模型中表现出正常的搔抓，但在干燥皮肤和 ACD 的慢性瘙痒模型中搔抓减少。相比之下，Cxcr3 小鼠中甲醛诱导的急性疼痛和完全弗氏佐剂诱导的慢性炎症性疼痛均减轻。此外，在丙酮和乙醚随后用水 (AEW) 诱导的干燥皮肤模型中，脊髓中 CXCR3 和 CXCL10 的表达增加。鞘内注射 CXCR3 拮抗剂可缓解 AEW 诱导的瘙痒。此外，在化合物 48/80 或 AEW 处理后，Cxcr3 小鼠的触摸诱发瘙痒（alloknesis）受到抑制。最后，AEW 诱导的星形胶质细胞激活在 Cxcr3 小鼠中受到抑制。综上所述，这些数据表明脊髓 CXCR3 介导慢性瘙痒和 alloknesis，靶向 CXCR3 可能为慢性瘙痒提供有效的治疗方法。
