In summary, this study demonstrated the following: (1) membrane cholesterol depletion preserves PAP-mediated antinociception through PI(4,5)P2 hydrolysis and (2) pain hypersensitivity that develops after TRPV1(+) neuron depletion-mediated neurodegeneration following RTX neuropathy is attributable to the downregulation of PAP analgesic signaling. This evidence concerns the gene TRPV1 and neuropathy.