Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, United States.
Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, Boston, MA, United States. Mr. Ren is now with the Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, United States.
Pain. 2019 May;160(5):1166-1174. doi: 10.1097/j.pain.0000000000001499.
Recent studies have made significant progress in identifying distinct populations of peripheral neurons involved in itch transmission, whereas the cellular identity of spinal interneurons that contribute to itch processing is still a debate. Combining genetic and pharmacological ablation of spinal excitatory neuronal subtypes and behavioral assays, we demonstrate that spinal somatostatin-positive (SOM) excitatory interneurons transmit pruritic sensation. We found that the ablation of spinal SOM/Lbx1 (SOM) neurons caused significant attenuation of scratching responses evoked by various chemical pruritogens (chemical itch). In an attempt to identify substrates of spinal itch neural circuit, we observed that spinal SOM neurons partially overlapped with neurons expressing natriuretic peptide receptor A (Npra), the receptor of peripheral itch transmitter B-type natriuretic peptide. Spinal SOM neurons, however, did not show any overlap with itch transmission neurons expressing gastrin-releasing peptide receptor in the dorsal spinal cord, and the gastrin-releasing peptide-triggered scratching responses were intact after ablating spinal SOM neurons. Dual ablation of SOM and Npra neurons in the spinal cord reduced chemical itch responses to a greater extent than ablation of SOM or Npra neurons alone, suggesting the existence of parallel spinal pathways transmitting chemical itch. Furthermore, we showed that SOM peptide modulated itch processing through disinhibition of somatostatin receptor 2A-positive inhibitory interneuron. Together, our findings reveal a novel spinal mechanism for sensory encoding of itch perception.
最近的研究在鉴定参与瘙痒传递的外周神经元的不同群体方面取得了重大进展，而有助于瘙痒处理的脊髓中间神经元的细胞身份仍然存在争议。我们结合遗传和药理学消融脊髓兴奋性神经元亚型以及行为测定，证明脊髓生长抑素阳性（SOM）兴奋性中间神经元传递瘙痒感觉。我们发现，脊髓 SOM/Lbx1（SOM）神经元的消融导致各种化学致痒原（化学性瘙痒）诱发的搔抓反应明显减弱。为了尝试鉴定脊髓瘙痒神经回路的底物，我们观察到脊髓 SOM 神经元与表达利钠肽受体 A（Npra）的神经元部分重叠，Npra 是外周瘙痒递质 B 型利钠肽的受体。然而，脊髓 SOM 神经元与在背侧脊髓中表达胃泌素释放肽受体的瘙痒传递神经元没有任何重叠，并且在消融脊髓 SOM 神经元后，胃泌素释放肽触发的搔抓反应仍然完整。脊髓 SOM 和 Npra 神经元的双重消融比单独消融 SOM 或 Npra 神经元更能减轻化学性瘙痒反应，这表明存在传递化学性瘙痒的并行脊髓途径。此外，我们表明 SOM 肽通过抑制生长抑素受体 2A 阳性抑制性中间神经元来调节瘙痒处理。总之，我们的发现揭示了一种用于瘙痒感知感觉编码的新型脊髓机制。
