Your browser doesn't support javascript.
loading
The Up-regulation of TNF-α Maintains Trigeminal Neuralgia by Modulating MAPKs Phosphorylation and BKCa Channels in Trigeminal Nucleus Caudalis.
Lu, Zhan-Ying; Fan, Juan; Yu, Li-Hua; Ma, Bei; Cheng, Li-Ming.
Afiliação
  • Lu ZY; Experimental Training Center of Basic Medical Science, Naval Medical University, Shanghai, China.
  • Fan J; Experimental Training Center of Basic Medical Science, Naval Medical University, Shanghai, China.
  • Yu LH; Experimental Training Center of Basic Medical Science, Naval Medical University, Shanghai, China.
  • Ma B; Experimental Training Center of Basic Medical Science, Naval Medical University, Shanghai, China.
  • Cheng LM; Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Division of Spine Surgery, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
Front Cell Neurosci ; 15: 764141, 2021.
Article em En | MEDLINE | ID: mdl-34899191
ABSTRACT
Trigeminal neuralgia (TN) is a severe chronic neuropathic pain. Despite numerous available medical interventions, the therapeutic effects are not ideal. To control the pain attacks, the need for more contemporary drugs continues to be a real challenge. Our previous study reported that Ca2+-activated K+ channels (BK Ca ) channels modulated by mitogen-activated protein kinases (MAPKs) in the trigeminal ganglia (TG) neurons play crucial roles in regulating TN, and some research studies demonstrated that inflammatory cytokine tumor necrosis factor alpha (TNF-α) could promote neuropathic pain. Meanwhile, the trigeminal nucleus caudalis (TNC), the first central site of the trigeminal nociceptive pathway, is responsible for processing sensory and pain signals from the peripheral orofacial area. Thus, this study is aimed to further investigate whether TNF-α and MAPKs phosphorylation in the TNC could mediate the pathogenesis of TN by modulating BK Ca channels. The results showed that TNF-α of the TNC region is upregulated significantly in the chronic constriction injury of infraorbital nerve (ION-CCI) rats model, which displayed persistent facial mechanical allodynia. The normal rats with target injection of exogenous TNF-α to the fourth brain ventricle behaved just like the ION-CCI model rats, the orofacial mechanical pain threshold decreased clearly. Meanwhile, the exogenous TNF-α increased the action potential frequency and reduced the BK Ca currents of TNC neurons significantly, which could be reversed by U0126 and SB203580, the inhibitors of MAPK. In addition, U0126, SB203580, and another MAPK inhibitor SP600125 could relieve the facial mechanical allodynia by being injected into the fourth brain ventricle of ION-CCI model rats, respectively. Taken together, our work suggests that the upregulation of TNF-α in the TNC region would cause the increase of MAPKs phosphorylation and then the negative regulation of BK Ca channels, resulting in the TN.
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Front Cell Neurosci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Front Cell Neurosci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China