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c-Jun/p38MAPK/ASIC3 pathways specifically activated by NGF through TrkA is crucial for mechanical allodynia development

Abstract : Mechanical allodynia is a cardinal sign of several inflammatory pain disorders where Nerve Growth Factor, a prototypic neurotrophin, plays a crucial role by binding to TrkA receptors. Here, we took the advantage of our generated knock-in mouse model expressing a chimeric TrkA/TrkC receptor that seems to not specifically develop mechanical allodynia following inflammation, to identify the TrkA downstream pathways involved in this phenomenon. We confirmed and extended that disrupting TrkA specific pathways leads to a specific deficit in mechanical hypersensitivity development following somatic (systemic NGF administration and paw incision) and to a lesser extent, visceral injuries. Despite a deficit in thin, mainly peptidergic, fibres innervation in TrkAC mice, thermal hyperalgesia development was not different from WT mice. Inflammatory reaction (oedema, IL-6 content), pain behaviours following intraplantar capsaicin as well as TRPV1 calcium imaging response of DRG neurons were similar between TrkAC and WT mice. This deficiency in mechanical allodynia development in TrkAC mice is likely due to the alteration of the expression of different TrkA transduction pathways (i.e. Akt, p38 MAPK and c-Jun) especially p38 MAPK, in the DRG cell bodies, ultimately leading to an alteration of at least, ASIC3 channel overexpression, known to participate in nociceptor mechanosensory function.
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https://hal.archives-ouvertes.fr/hal-02464551
Contributor : Sébastien Poulain <>
Submitted on : Wednesday, November 25, 2020 - 10:09:56 AM
Last modification on : Tuesday, February 23, 2021 - 1:32:01 PM
Long-term archiving on: : Friday, February 26, 2021 - 6:29:48 PM

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Tanguy Chaumette, Lauriane Delay, Julie Barbier, Ludivine Boudieu, Youssef Aissouni, et al.. c-Jun/p38MAPK/ASIC3 pathways specifically activated by NGF through TrkA is crucial for mechanical allodynia development. PAIN, Elsevier, 2020, pp.1. ⟨10.1097/j.pain.0000000000001808⟩. ⟨hal-02464551⟩

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