Transplant restoration of spinal cord inhibitory controls ameliorates neuropathic itch
Transplant restoration of spinal cord inhibitory controls ameliorates neuropathic itch
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DOI：
10.1172/jci75214
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发表时间：
2014-08-01
影响因子：
15.9
通讯作者：
Basbaum, Allan I.
中科院分区：
文献类型：
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作者：
Braz, Joao M.;Juarez-Salinas, Dina;Basbaum, Allan I.
痛觉（痒）信息的传递涉及脊髓内的特定神经回路，这些神经回路与传递疼痛信息的神经回路不同。这些瘙痒特异性回路由背角中的抑制性中间神经元进行紧张性调节。与这些发现相一致，先前已经报道，在携带转录因子Bhlhb5缺失的小鼠中，GABA能中间神经元的损失产生严重的慢性瘙痒的非缓解性病症。在这里，我们测试的假设，BHLHB5缺陷的动物神经性瘙痒可以通过恢复抑制控制脊髓移植和整合的前体皮质抑制性中间神经元来自胚胎内侧神经节隆起的治疗。我们专门针对受影响最严重的身体区域的脊髓神经支配进行移植。接受移植的BHLHB5缺陷小鼠表现出过度抓挠的大幅减少和皮肤病变的显著消退。相比之下，在假处理的小鼠中，抓挠持续存在，皮肤病变随着时间的推移而恶化。总之，这些结果表明，细胞介导的抑制性对照的恢复具有作为神经性瘙痒的强大的基于细胞的疗法的潜力，其不仅改善慢性瘙痒的症状，而且还可以改变疾病。
The transmission of pruritoceptive (itch) messages involves specific neural circuits within the spinal cord that are distinct from those that transmit pain messages. These itch-specific circuits are tonically regulated by inhibitory interneurons in the dorsal horn. Consistent with these findings, it has previously been reported that loss of GABAergic interneurons in mice harboring a deletion of the transcription factor Bhlhb5 generates a severe, nonremitting condition of chronic itch. Here, we tested the hypothesis that the neuropathic itch in BHLHB5-deficient animals can be treated by restoring inhibitory controls through spinal cord transplantation and integration of precursors of cortical inhibitory interneurons derived from the embryonic medial ganglionic eminence. We specifically targeted the transplants to segments of the spinal cord innervated by areas of the body that were most severely affected. BHLHB5-deficient mice that received transplants demonstrated a substantial reduction of excessive scratching and dramatic resolution of skin lesions. In contrast, the scratching persisted and skin lesions worsened over time in sham-treated mice. Together, these results indicate that cell-mediated restoration of inhibitory controls has potential as a powerful, cell-based therapy for neuropathic itch that not only ameliorates symptoms of chronic itch, but also may modify disease.