The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity

Sci Rep. 2017 Mar 27;7(1):446. doi: 10.1038/s41598-017-00591-0.


Chemotherapy-induced peripheral neuropathic pain (CIPN) is a common and severe debilitating side effect of many widely used cytostatics. However, there is no approved pharmacological treatment for CIPN available. Among other substances, oxaliplatin causes CIPN in up to 80% of treated patients. Here, we report the involvement of the G-protein coupled receptor G2A (GPR132) in oxaliplatin-induced neuropathic pain in mice. We found that mice deficient in the G2A-receptor show decreased mechanical hypersensitivity after oxaliplatin treatment. Lipid ligands of G2A were found in increased concentrations in the sciatic nerve and dorsal root ganglia of oxaliplatin treated mice. Calcium imaging and patch-clamp experiments show that G2A activation sensitizes the ligand-gated ion channel TRPV1 in sensory neurons via activation of PKC. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / deficiency
  • Cell Cycle Proteins / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Enzyme Activation / drug effects
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / pathology
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / metabolism*
  • Hyperalgesia / pathology
  • Linoleic Acids, Conjugated
  • Mice, Inbred C57BL
  • Neuralgia / chemically induced*
  • Neuralgia / metabolism*
  • Neuralgia / pathology
  • Organoplatinum Compounds / adverse effects*
  • Oxaliplatin
  • Protein Kinase C / metabolism
  • Receptors, G-Protein-Coupled / deficiency
  • Receptors, G-Protein-Coupled / metabolism*
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / pathology
  • Sensory Receptor Cells / metabolism
  • TRPV Cation Channels / deficiency
  • TRPV Cation Channels / metabolism


  • Cell Cycle Proteins
  • G2A receptor
  • Linoleic Acids, Conjugated
  • Organoplatinum Compounds
  • Receptors, G-Protein-Coupled
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Oxaliplatin
  • 9-hydroxy-10,12-octadecadienoic acid
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C