This study demonstrated that membrane integrity is in involved in RTX neuropathy through two mechanisms: (1) the prevention of allodynic pain by MβC-mediated cholesterol depletion and (2) the recurrence of pain caused by the dysfunction of PAP-mediated antinociception related to TRPV1(+) neuron depletion–mediated neurodegeneration. Here, TRPV1 is linked to neuropathy.