One of the most frequently used agents causing CIPN is the platinum derivate oxaliplatin. Currently, there are no drugs available for the prevention or effective treatment of CIPN 1, 3. CIPN is one of the major reasons for delay or discontinuation of chemotherapy and is therefore responsible for decreased chemotherapeutic efficacy and loss of quality of life 1, 2. Based on these findings, we conclude that targeting G2A may be a promising approach to reduce oxaliplatin-induced TRPV1-sensitization and the hyperexcitability of sensory neurons and thereby to reduce pain in patients treated with this chemotherapeutic agent.Ĭhemotherapy-induced peripheral neuropathic pain (CIPN) is a severe adverse event of cytostatic drugs during cancer therapy. Calcium imaging and patch-clamp experiments show that G2A activation sensitizes the ligand-gated ion channel TRPV1 in sensory neurons via activation of PKC. Lipid ligands of G2A were found in increased concentrations in the sciatic nerve and dorsal root ganglia of oxaliplatin treated mice. We found that mice deficient in the G2A-receptor show decreased mechanical hypersensitivity after oxaliplatin treatment. Here, we report the involvement of the G-protein coupled receptor G2A (GPR132) in oxaliplatin-induced neuropathic pain in mice. Among other substances, oxaliplatin causes CIPN in up to 80% of treated patients.
However, there is no approved pharmacological treatment for CIPN available. Chemotherapy-induced peripheral neuropathic pain (CIPN) is a common and severe debilitating side effect of many widely used cytostatics.
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