Virginia Thornley, M.D., Neurologist, Epileptologist

March 1, 2018

Introduction

As more and more survivors of cancer grow in number, there is increasing interest in treatments for chemotherapy-induced toxicity. Chemotherapy-induced peripheral neuropathies are one of the most common neurotoxic side effects prevalent in cancer survivors. Attention is drawn to alternative treatments such as stem cell research as at times, this condition may be resistant to treatment with conventional agents.

Common chemotherapeutic agents that cause neuropathy

Some of the most common chemotherapeutic agents that cause peripheral neuropathy include vincristine, oxaliplatin, cisplatin, paclitaxel. The sites most prevalent with neurotoxic effects include the dorsal root ganglion, peripheral nerves, satellite cells and Schwann cells as well as glial cells in the spinal cord.

Some mechanisms that are proposed that cause neural damage include glutamate activation, increased intracellular oxygen changes, DNA damage, altered cell repair, alteration in ion channels, change in mitochondrial metabolism and MAP kinase activation.

Role of stem cell in chemotherapy-induced peripheral neuropathy and other novel treatment approaches

In chemotherapy for colon cancer, oxaliplatin can cause chemo-induced peripheral neuropathy in 50% of patients. In one study, pain relieving qualities of mesenchymal stem cells were studied. Rat adipose stem cells were applied to rats with chemotherapy-induced peripheral neuropathy in one animal model. An IV injection of rat adipose stem cell injected into the rate of neuropathy revealed a reduced hypersensitivity to the noxious effects. Repeated injections every 5 days produced the same results. VEGF was noted to be upregulated or vascular endothelial growth factor. When a monoclonal antibody used against this VEGF was applied there was reduced pain, suggesting a role of VEGF in pain. Adult adipose mesenchymal stem cell may represent a novel approach to alleviating pain from chemotherapy-induced peripheral neuropathy. This rat model also elucidated the role an antibody against VEGF can play in the treatment of peripheral neuropathy caused by chemotherapy.

Pain might also be influenced by increased gap junction coupling during chemotherapy. In one study, using a gap coupling blocker, the pain was alleviated in chemotherapy-induced peripheral neuropathy in mice producing an analgesic effect(3).

Reference:

1. Di Cesare, et al, “Adipose-derived stem cells decrease pain in a  rat model of oxaliplatin-induced neuropathy: role of VEGF-A modulation,” Neuropharmacology, 2018, Mar., 15; 131:166-175.
2. Carozzi, et al, “Chemotherapy-induced neuropathy: what do we know now?” Neuroscience Letter, 2015, Jun., 2(596):90-107.
3. Warwick, et al, “The contribution of satellite glial cells to chemotherapy-induced neuropathic pain,” European Journal of Pain, 2013, Apr., 17(4):571-80.