Bortezomib, an anticancer
drug for
multiple myeloma and
mantle cell lymphoma, causes severe adverse events and leads to
peripheral neuropathy. The associated neuropathy limits the use of
bortezomib and could lead to discontinuation of the treatment; therefore, effective intervention is crucial. In the present study, we statistically searched for a
drug that could alleviate
bortezomib-induced
peripheral neuropathy using adverse event self-reports. We observed that specific inhibitors of the mechanistic target of
rapamycin (mTOR) lowered the incidence of
bortezomib-induced
peripheral neuropathy. These findings were experimentally validated in mice, which exhibited long-lasting mechanical
hypersensitivity after repeated
bortezomib treatment. This effect was inhibited for hours after a systemic injection with
rapamycin or
everolimus in a dose-dependent manner.
Bortezomib-induced
allodynia was accompanied by the activation of spinal astrocytes, and
intrathecal injection of
mTOR inhibitors or an inhibitor of
ribosomal protein S6 kinase 1, a downstream target of mTOR, exhibited considerable
analgesic effects in a dose-dependent manner. These results suggest that
mTOR inhibitors, which are readily available to patients prescribed
bortezomib, are one of the most effective
therapeutics for
bortezomib-induced
peripheral neuropathy.