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Histamine H4 receptor and TRPV1 mediate itch induced by cadaverine, a metabolite of the microbiome.
Sun, Shi-Yu; Yin, Xi; Ma, Jun-Yi; Wang, Xue-Long; Xu, Xue-Mei; Wu, Jing-Ni; Zhang, Cheng-Wei; Lu, Ying; Liu, Tong; Zhang, Li; Kang, Pei-Pei; Wu, Bin; Zhou, Guo-Kun.
Afiliación
  • Sun SY; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong, China.
  • Yin X; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong, China.
  • Ma JY; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong, China.
  • Wang XL; Department of Thoracic Surgery, Capital Medical University Electric Power Teaching Hospital, Beijing, China.
  • Xu XM; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong, China.
  • Wu JN; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong, China.
  • Zhang CW; Department of Thoracic Surgery, Capital Medical University Electric Power Teaching Hospital, Beijing, China.
  • Lu Y; Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, China.
  • Liu T; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong, China.
  • Zhang L; Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • Kang PP; Department of Anesthesiology, Affiliated Tumor Hospital of Nantong University, Nantong, China.
  • Wu B; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong, China.
  • Zhou GK; Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong, China.
Mol Pain ; 20: 17448069241272149, 2024.
Article en En | MEDLINE | ID: mdl-39079948
ABSTRACT
Cadaverine is an endogenous metabolite produced by the gut microbiome with various activity in physiological and pathological conditions. However, whether cadaverine regulates pain or itch remains unclear. In this study, we first found that cadaverine may bind to histamine 4 receptor (H4R) with higher docking energy score using molecular docking simulations, suggesting cadaverine may act as an endogenous ligand for H4R. We subsequently found intradermal injection of cadaverine into the nape or cheek of mice induces a dose-dependent scratching response in mice, which was suppressed by a selective H4R antagonist JNJ-7777120, transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine and PLC inhibitor U73122, but not H1R antagonist or TRPA1 antagonist or TRPV4 antagonist. Consistently, cadaverine-induced itch was abolished in Trpv1-/- but not Trpa1-/- mice. Pharmacological analysis indicated that mast cells and opioid receptors were also involved in cadaverine-induced itch in mice. scRNA-Seq data analysis showed that H4R and TRPV1 are mainly co-expressed on NP2, NP3 and PEP1 DRG neurons. Calcium imaging analysis showed that cadaverine perfusion enhanced calcium influx in the dissociated dorsal root ganglion (DRG) neurons, which was suppressed by JNJ-7777120 and capsazepine, as well as in the DRG neurons from Trpv1-/- mice. Patch-clamp recordings found that cadaverine perfusion significantly increased the excitability of small diameter DRG neurons, and JNJ-7777120 abolished this effect, indicating involvement of H4R. Together, these results provide evidences that cadaverine is a novel endogenous pruritogens, which activates H4R/TRPV1 signaling pathways in the primary sensory neurons.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Prurito / Cadaverina / Canales Catiónicos TRPV / Ganglios Espinales / Ratones Endogámicos C57BL Límite: Animals / Humans / Male Idioma: En Revista: Mol Pain Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Prurito / Cadaverina / Canales Catiónicos TRPV / Ganglios Espinales / Ratones Endogámicos C57BL Límite: Animals / Humans / Male Idioma: En Revista: Mol Pain Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA / PSICOFISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos