The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4

0448387 - FGÚ 2016 RIV US eng J - Journal Article
Li, Y. - Adámek, Pavel - Zhang, H. - Tatsui, C. E. - Rhines, L. D. - Mrózková, Petra - Li, Q. - Kosturakis, A. K. - Cassidy, R. M. - Harrison, D. S. - Cata, J. P. - Sapire, K. - Zhang, HM. - Kennamer-Chapman, R. M. - Jawad, A. B. - Ghetti, A. - Yan, J. - Paleček, Jiří - Dougherty, P. M.
The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4.
Journal of Neuroscience. Roč. 35, č. 39 (2015), s. 13487-13500. ISSN 0270-6474. E-ISSN 1529-2401
R&D Projects: GA MŠMT(CZ) LH12058; GA MŠMT(CZ) EE2.3.30.0025; GA ČR(CZ) GA15-11138S
Institutional support: RVO:67985823
Keywords : cancer * dorsal horn * DRG * neuropathy
Subject RIV: FH - Neurology
Impact factor: 5.924, year: 2015

In this original work, it is shown for the first time that paclitaxel activates peripheral sensory and spinal neurons directly and sensitizes these cells to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated capsaicin responses via Toll-like receptor 4 (TLR4) in multiple species. A direct functional interaction between TLR4 and TRPV1 is shown in rat and human dorsal root ganglion neurons, TLR4/TRPV1-coexpressing HEK293 cells, and in both rat and mouse spinal cord slices. Moreover, this is the first study to show that this interaction plays an important role in the generation of behavioral hypersensitivity in paclitaxel-related neuropathy. The key translational implications are that TLR4 and TRPV1 antagonists may be useful in the prevention and treatment of chemotherapy-induced peripheral neuropathy in humans
Permanent Link: http://hdl.handle.net/11104/0250100