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Pain ; 160(5): 1166-1174, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30913166

RESUMO

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.


Assuntos
Interneurônios/metabolismo , Prurido/induzido quimicamente , Prurido/patologia , Somatostatina/metabolismo , Medula Espinal/patologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Inibidores da Angiogênese/farmacologia , Animais , Cloroquina/toxicidade , Modelos Animais de Doenças , Técnicas In Vitro , Interneurônios/fisiologia , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Nitrobenzoatos/farmacologia , Técnicas de Patch-Clamp , Proteínas Proto-Oncogênicas c-fos/metabolismo , Somatostatina/genética , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , p-Metoxi-N-metilfenetilamina/toxicidade , Proteínas tau/genética , Proteínas tau/metabolismo
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