Gene therapy for nerve pain

The 90 percent of cancer patients who experience pain due to nerve damage caused by tumors, surgery, chemotherapy or radiation may someday be helped by gene therapy, according to a new MD Anderson study published in Cell Reports.

The study in rats showed transferring a gene known as KCC2 into the spinal canal restored chloride levels gone awry after nerve injury.

“We found that delivery of KCC2 produced a complete and long-lasting reversal of nerve injury-induced pain hypersensitivity by restoring chloride homeostasis,” said Hui-Lin Pan, M.D., Ph.D., professor of Anesthesiology and Perioperative Medicine. “This information significantly advances our understanding of these processes and provides a promising gene therapy strategy for treating unmanageable neuropathic pain.”

The proper balance of chloride, a mineral crucial for nerve cell function, is thrown off kilter by nerve damage associated with surgery or the toxic aspects of standard chemotherapies. This causes the inhibitory neurotransmitters GABA and glycine to become less effective and increases activity by excitatory nerve receptors known as NMDA receptors.

“Diminished synaptic inhibition by GABA and glycine and increased NMDA receptor activity are two key mechanisms underlying neuropathic pain,” said Pan. “However the reciprocal relationship between the two is unclear. By using KCC2 gene transfer, we were able to restore chloride balance which also unexpectedly normalized NMDA receptor activity increased by nerve injury.”

Chronic neuropathic pain is a major, debilitating clinical challenge that is difficult to treat. Existing analgesics including anti-depressants, opioids and gabapentinoids have limited efficacy and often produce intolerable side effects.

“The development of highly effective patient treatments with minimal effects is urgently needed,” said Pan.

Learn more about gene therapy for neuropathic pain, go to MD Anderson's website.