MedicalResearch.com Interview with:
Hui-Lin Pan, MD, PhD
Helen T. Hawkins Distinguished Professor
and Deputy Division Head for Research
Division of Anesthesiology and Critical Care, Unit 110
The University of Texas MD Anderson Cancer Center
MedicalResearch.com: What is the background for this study?
Dr. Hui-Lin Pan: Chronic nerve pain caused by damage to the peripheral nerve is a debilitating health problem and remains very difficult to treat. Sensory neurons in the spinal cord are normally inhibited by inhibitory neurotransmitters (GABA and glycine) to regulate transmission of painful information. A major feature of nerve injury-induced chronic pain is reduced spinal cord inhibition, resulting from diminished activity of a chloride transporter called KCC2. In this study, we investigated whether increasing KCC2 expression at the spinal level using a lentiviral vector can restore KCC2 activity, thereby reducing chronic nerve pain.
MedicalResearch.com: What are the main findings?
Dr. Hui-Lin Pan: We found that delivering the KCC2 gene to the spinal canal induced a long-lasting KCC2 expression and fully restored KCC2 activity in both spinal cord and peripheral sensory neurons. We also found unexpectedly that restoring KCC2 activity normalized the increased glutamate NMDA receptor activity, which serves to amplify the pain signal at the spinal cord level. Importantly, KCC2 gene delivery completely and persistently eliminated pain hypersensitivity induced by nerve injury.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Hui-Lin Pan: Viral vector-mediated KCC2 delivery may be a promising gene therapy to treat patients with unmanageable chronic nerve pain.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Hui-Lin Pan: We need to further determine the mutual relationship between KCC2-mediated neuron inhibition and NMDA receptor-mediated neuron excitation in processing painful information. We also need to conduct translational research to determine the efficacy and safety of using lentiviral vectors to deliver KCC2 gene for treating chronic nerve pain in patients.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Lingyong Li et al. Chloride Homeostasis Critically Regulates Synaptic NMDA Receptor Activity in Neuropathic Pain. Cell Reports, May 2016 DOI: 10.1016/j.celrep.2016.04.039
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