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Hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) ion channels drive pain in mouse models of diabetic neuropathy.
Tsantoulas, Christoforos; Laínez, Sergio; Wong, Sara; Mehta, Ishita; Vilar, Bruno; McNaughton, Peter A.
Afiliación
  • Tsantoulas C; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK.
  • Laínez S; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK.
  • Wong S; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK.
  • Mehta I; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK.
  • Vilar B; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK.
  • McNaughton PA; Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK. peter.mcnaughton@kcl.ac.uk.
Sci Transl Med ; 9(409): eaam6072, 2017 Sep 27.
Article en En | MEDLINE | ID: mdl-28954930
Diabetic patients frequently suffer from continuous pain that is poorly treated by currently available analgesics. We used mouse models of type 1 and type 2 diabetes to investigate a possible role for the hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) ion channels as drivers of diabetic pain. Blocking or genetically deleting HCN2 channels in small nociceptive neurons suppressed diabetes-associated mechanical allodynia and prevented neuronal activation of second-order neurons in the spinal cord in mice. In addition, we found that intracellular cyclic adenosine monophosphate (cAMP), a positive HCN2 modulator, is increased in somatosensory neurons in an animal model of painful diabetes. We propose that the increased intracellular cAMP drives diabetes-associated pain by facilitating HCN2 activation and consequently promoting repetitive firing in primary nociceptive nerve fibers. Our results suggest that HCN2 may be an analgesic target in the treatment of painful diabetic neuropathy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dolor / Canales de Potasio / Neuropatías Diabéticas / Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización Límite: Animals Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dolor / Canales de Potasio / Neuropatías Diabéticas / Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización Límite: Animals Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos