PuSH - Publication Server of Helmholtz Zentrum München: Brain-derived neurotrophic factor stimulation of T-type Ca2+ channels in sensory neurons contributes to increased peripheral pain sensitivity.

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Wang, H.* ; Wei, Y.* ; Pu, Y.* ; Jiang, D. ; Jiang, X.* ; Zhang, Y.* ; Tao, J.*

Brain-derived neurotrophic factor stimulation of T-type Ca2+ channels in sensory neurons contributes to increased peripheral pain sensitivity.

Sci. Signal. 12:eaaw2300 (2019)

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Open Access Green as soon as Postprint is submitted to ZB.

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Although brain-derived neurotrophic factor (BDNF) is implicated in the nociceptive signaling of peripheral sensory neurons, the underlying mechanisms remain largely unknown. Here, we elucidated the effects of BDNF on the neuronal excitability of trigeminal ganglion (TG) neurons and the pain sensitivity of rats mediated by T-type Ca2+ channels. BDNF reversibly and dose-dependently enhanced T-type channel currents through the activation of tropomyosin receptor kinase B (TrkB). Antagonism of phosphatidylinositol 3-kinase (PI3K) but not of its downstream target, the kinase AKT, abolished the BDNF-induced T-type channel response. BDNF application activated p38 mitogen-activated protein kinase (MAPK), and this effect was prevented by inhibition of PI3K but not of protein kinase A (PKA). Antagonism of either PI3K or p38 MAPK prevented the BDNF-induced stimulation of PKA activity, whereas PKA inhibition blocked the BDNF-mediated increase in T-type currents. BDNF increased the rate of action potential firing in TG neurons and enhanced the pain sensitivity of rats to mechanical stimuli. Moreover, inhibition of TrkB signaling abolished the increased mechanical sensitivity in a rat model of chronic inflammatory pain, and this effect was attenuated by either T-type channel blockade or knockdown of the channel Ca(v)3.2. Together, our findings indicate that BDNF enhances T-type currents through the stimulation of TrkB coupled to PI3K-p38-PKA signaling, thereby inducing neuronal hyperexcitability of TG neurons and pain hypersensitivity in rats.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Gated Calcium-channels; Protein-kinase-c; Receptor Stimulation; Strain Differences; Redox Modulation; Neuropathic Pain; Growth-factor; Nerve Injury; P38 Mapk; Rat

ISSN (print) / ISBN 1945-0877

e-ISSN 1937-9145

Journal Science Signaling

Quellenangaben Volume: 12, Issue: 600, Article Number: eaaw2300

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Lung Health and Immunity (LHI)