School of Psychology and Neuroscience, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan.
Elife. 2023 Jul 25;12:RP86633. doi: 10.7554/eLife.86633.
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 the adult mouse spinal cord. 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.
躯体感觉信息在脊髓背角的神经元网络中进行处理。据报道，在发育过程中或永久性表达神经肽 Y (NPY) 的抑制性中间神经元可抑制机械性瘙痒，而对疼痛没有影响。在这里，我们研究了成年小鼠脊髓中持续表达 NPY 的中间神经元 (NPY-INs) 的作用。我们发现，化学遗传激活 NPY-INs 可减少与急性疼痛和致痒剂诱发瘙痒相关的行为，而沉默它们会导致依赖胃泌素释放肽受体表达的细胞的瘙痒反应过度。正如我们之前的研究预测的那样，抑制另一群抑制性中间神经元（表达强啡肽）也会增加瘙痒，但程度较小。重要的是，NPY-IN 的激活也减少了炎症性和神经性疼痛的行为迹象。这些结果表明，NPY-INs 在脊髓水平上调节疼痛和瘙痒的传递，因此代表了病理性疼痛和瘙痒的潜在治疗靶点。
