Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling-猫眼课题宝

DOI：

10.1101/2023.02.10.528013

发表时间：

2023-03

期刊：

bioRxiv

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

K. Boyle;E. Polgár;M. Gutierrez-Mecinas;A. Dickie;Andrew H. Cooper;Andrew M. Bell;M. Evelline Jumolea;Adrián Casas-Benito;Masahiko Watanabe;D. Hughes;Gregory A Weir;J. Riddell;A. Todd

躯体感觉信息是由脊髓背角中复杂的中间神经元网络处理的。据报道，表达神经肽Y（NPY）的抑制性中间神经元，无论是永久性的还是在发育过程中，都能抑制机械性瘙痒，对疼痛没有影响。在这里，我们调查的作用，继续表达NPY（NPY-INs）在成年期的中间神经元。我们发现，NPY-INs的化学发生激活减少了与急性疼痛和促炎原诱发的瘙痒相关的行为，而沉默它们会导致依赖于表达胃泌素释放肽受体的细胞的过度瘙痒反应。正如我们以前的研究所预测的那样，另一群抑制性中间神经元（表达强啡肽的那些）的沉默也会增加瘙痒，但程度较轻。重要的是，NPY-IN的激活也减少了炎症和神经性疼痛的行为体征.这些结果表明，NPY-IN在脊髓水平上控制疼痛和瘙痒的传递，因此代表了病理性疼痛和瘙痒的潜在治疗靶点。

Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory interneurons that express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here we investigate the role of interneurons that continue to express NPY (NPY-INs) in adulthood. We find that chemogenetic activation of NPY-INs reduces behaviours associated with acute pain and pruritogen-evoked itch, whereas silencing them causes exaggerated itch responses that depend on cells expressing the gastrin-releasing peptide receptor. As predicted by our previous studies, silencing of another population of inhibitory interneurons (those expressing dynorphin) also increases itch, but to a lesser extent. Importantly, NPY- IN activation also reduces behavioural signs of inflammatory and neuropathic pain. These results demonstrate that NPY-INs gate pain and itch transmission at the spinal level, and therefore represent a potential treatment target for pathological pain and itch.

Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling

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