Gene Therapy Shows Potential to Reverse Cancer-Related Nerve Pain

Unbalance chloride levels be restored to stop cancer-related neuropathic pain.

A recent study found that neuropathic pain relating to cancer could possibly be treated by transferring the gene KCC2 into the spinal canal.

Approximately 90% of cancer patients develop neuropathic pain due to nerve damage caused by tumors, surgery, chemotherapy, or radiation, according to the study published in Cell Reports.

In the study, researchers used rat models to transfer KCC2 into the spinal canal and found that it restored chloride levels that became imbalanced after nerve injury. Researchers said this could potentially be used to treat chronic pain from diabetic neuropathy and spinal cord injury as well.

"We found that delivery of KCC2 produced a complete and long-lasting reversal of nerve injury-induced pain hypersensitivity by restoring chloride homeostasis," said researcher Hui-Lin Pan, MD, PhD. "This information significantly advances our understanding of these processes and provides a promising gene therapy strategy for treating unmanageable neuropathic pain."

Chloride, which is the mineral responsible for nerve cell function, can be thrown off balance by nerve damage from surgery or chemotherapy. This causes the inhibitory neurotransmitters GABA and glycine to be less effective and increase activity of excitatory nerve receptors, NMDA receptors.

"Diminished synaptic inhibition by GABA and glycine and increased NMDA receptor activity are two key mechanisms underlying neuropathic pain," Dr Pan said. "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."

The results of this study provide evidence that chloride homeostasis is crucial in the regulation of NDMA receptors in chronic pain, the researchers noted.

"The development of highly effective patient treatments with minimal effects is urgently needed," Dr Pan concluded. "Our study addressed the need to change the intracellular concentration of chloride which can profoundly alter the strength and polarity of GABA and glycine."