TY  - JOUR
A1  - Rimola, Vittoria
A1  - Osthues, Tabea
A1  - Königs, Vanessa
A1  - Geisslinger, Gerd
A1  - Sisignano, Marco
T1  - Oxaliplatin causes transient changes in TRPM8 channel activity
T2  - International journal of molecular sciences
N2  - Oxaliplatin is a third-generation platinum-based anticancer drug that is widely used as first-line treatment for colorectal carcinoma. Patients treated with oxaliplatin develop an acute peripheral pain several hours after treatment, mostly characterized by cold allodynia as well as a long-term chronic neuropathy. These two phenomena seem to be causally connected. However, the underlying mechanisms that trigger the acute peripheral pain are still poorly understood. Here we show that the activity of the transient receptor potential melastatin 8 (TRPM8) channel but not the activity of any other member of the TRP channel family is transiently increased 1 h after oxaliplatin treatment and decreased 24 h after oxaliplatin treatment. Mechanistically, this is connected with activation of the phospholipase C (PLC) pathway and depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) after oxaliplatin treatment. Inhibition of the PLC pathway can reverse the decreased TRPM8 activity as well as the decreased PIP2-concentrations after oxaliplatin treatment. In summary, these results point out transient changes in TRPM8 activity early after oxaliplatin treatment and a later occurring TRPM8 channel desensitization in primary sensory neurons. These mechanisms may explain the transient cold allodynia after oxaliplatin treatment and highlight an important role of TRPM8 in oxaliplatin-induced acute and neuropathic pain.
KW  - oxaliplatin
KW  - TRPM8
KW  - desensitization
KW  - acute pain
KW  - neuropathic pain
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/61247
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-612479
SN  - 1422-0067
VL  - 22
IS  - 9, art. 4962
SP  - 1
EP  - 16
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -