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N-methyl D-aspartate receptor subtype 2B antagonist, Ro 25-6981, attenuates neuropathic pain by inhibiting postsynaptic density 95 expression.
Huang, Ling-Er; Guo, Shao-Hui; Thitiseranee, Lalita; Yang, Yan; Zhou, Yan-Feng; Yao, Yong-Xing.
Afiliação
  • Huang LE; First Affiliated Hospital, Zhejiang University School of Medicine, Department of Anesthesia, Hangzhou, 310003, P.R. China.
  • Guo SH; First Affiliated Hospital, Zhejiang University School of Medicine, Department of Anesthesia, Hangzhou, 310003, P.R. China.
  • Thitiseranee L; Zhejiang University School of Medicine, Hangzhou, 310016, P.R. China.
  • Yang Y; Zhejiang University School of Medicine, Centre for Neuroscience, Hangzhou, 310016, P.R. China.
  • Zhou YF; First Affiliated Hospital, Zhejiang University School of Medicine, Department of Anesthesia, Hangzhou, 310003, P.R. China.
  • Yao YX; First Affiliated Hospital, Zhejiang University School of Medicine, Department of Anesthesia, Hangzhou, 310003, P.R. China. yaoyongxing@zju.edu.cn.
Sci Rep ; 8(1): 7848, 2018 05 18.
Article em En | MEDLINE | ID: mdl-29777135
Postsynaptic density-95 (PSD-95) is a synaptic scaffolding protein that plays a crucial role in the development of neuropathic pain. However, the underlying mechanism remains unclear. To address the role of PSD-95 in N-methyl-D-aspartate receptor subtype 2B (NR2B) -mediated chronic pain, we investigated the relationship between PSD-95 activation and NR2B function in the spinal cord, by using a rat model of sciatic nerve chronic constriction injury (CCI). We demonstrate that the expression levels of total PSD-95 and cAMP response element binding protein (CREB), as well as phosphorylated NR2B, PSD-95, and CREB, in the spinal dorsal horn, and the interaction of NR2B with PSD-95 were increased in the CCI animals. Intrathecal injection of the selective NR2B antagonist Ro 25-6981 increased paw withdrawal latency, in a thermal pain assessment test. Moreover, repeated treatment with Ro 25-6981 markedly attenuated the thermal hypersensitivity, and inhibited the CCI-induced upregulation of PSD-95 in the spinal dorsal horn. Furthermore, intrathecal injection of the PSD-95 inhibitor strikingly reversed the thermal and mechanical hyperalgesia. Our results suggest that blocking of NR2B signaling in the spinal cord could be used as a therapeutic candidate for treating neuropathic pain.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenóis / Piperidinas / Receptores de N-Metil-D-Aspartato / Proteína 4 Homóloga a Disks-Large / Neuralgia Limite: Animals Idioma: En Revista: Sci Rep Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenóis / Piperidinas / Receptores de N-Metil-D-Aspartato / Proteína 4 Homóloga a Disks-Large / Neuralgia Limite: Animals Idioma: En Revista: Sci Rep Ano de publicação: 2018 Tipo de documento: Article