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IL-33 induces orofacial neuropathic pain through Fyn-dependent phosphorylation of GluN2B in the trigeminal spinal subnucleus caudalis.
Kimura, Yuki; Hayashi, Yoshinori; Hitomi, Suzuro; Ikutame, Daisuke; Urata, Kentaro; Shibuta, Ikuko; Sakai, Atsushi; Ni, Junjun; Iwata, Koichi; Tonogi, Morio; Shinoda, Masamichi.
Afiliación
  • Kimura Y; Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry, Tokyo, Japan.
  • Hayashi Y; Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan. Electronic address: hayashi.yoshinori@nihon-u.ac.jp.
  • Hitomi S; Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.
  • Ikutame D; Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo, Japan.
  • Urata K; Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo, Japan.
  • Shibuta I; Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.
  • Sakai A; Department of Pharmacology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
  • Ni J; Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing, China.
  • Iwata K; Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.
  • Tonogi M; Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry, Tokyo, Japan.
  • Shinoda M; Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.
Brain Behav Immun ; 99: 266-280, 2022 01.
Article en En | MEDLINE | ID: mdl-34715301
Orofacial neuropathic pain can cause considerable disruptions in patients' daily lives, especially because of a lack of effective medications as its underlying causative mechanisms are not fully understood. Here, we found neuron-specific expression of the interleukin (IL)-33 receptor in the trigeminal spinal subnucleus caudalis (Vc), distinct from the spinal dorsal horn. Reduction in head withdrawal threshold in response to von Frey filament stimulation of the whisker pad skin was inversely correlated with the upregulation of IL-33 in the Vc after infraorbital nerve injury (IONI). Neutralization of IL-33 in the Vc alleviated mechanical allodynia in the whisker pad skin after IONI; conversely, intracisternal administration of IL-33 elicited mechanical allodynia in the whisker pad skin, which was relieved by GluN2B antagonism. Moreover, IL-33 triggered the potentiation of GluN2B-containing N-methyl-D-aspartate receptor-mediated synaptic currents and phosphorylation of synaptosomal GluN2B in the Vc, whereas IONI-induced GluN2B phosphorylation was inhibited by neutralization of IL-33 in the Vc. IL-33-induced GluN2B phosphorylation was mediated by phosphorylation of Fyn kinase, and inhibition of the Fyn kinase pathway prevented the development of IL-33-induced mechanical allodynia. Our findings provide insights into a new mechanism by which IL-33 directly regulates synaptic transmission and suggest that IL-33 signaling could be a candidate target for therapeutic interventions for orofacial neuropathic pain.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de N-Metil-D-Aspartato / Neuralgia Límite: Animals Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de N-Metil-D-Aspartato / Neuralgia Límite: Animals Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos