A common complication of spinal cord injury (SCI) is neuropathic pain, a condition which causes feelings of extreme pain in response to harmless stimuli, such as being lightly touched. Chronic neuropathic pain presents a quality of life concern for SCI patients and is particularly challenging to overcome. The standard treatment for neuropathic pain includes pharmaceutical drugs, which are often administered through an epidural or could lead to drug tolerance and misuse (i.e., opioids).
In addition, neuropathic pain is often associated with specific segments of the spine, but pharmaceutical drugs are currently unable to target these segments, leaving larger areas of the spine susceptible to drug side effects. Previous studies have found that the most effective method for eliminating neuropathic pain in SCI patients is a targeted therapy which promotes the release of GABA (an inhibitory neurotransmitter) in affected spinal cord neurons.
In a preclinical animal study, a team of researchers sought to design a solution that increases GABA in spinal cord neurons using gene therapy to promote GABA-related genes GAD65 and VGAT. The researchers administered the gene therapy through a lumbar injection and observed the behavioral and chemical effects of GAD65 and VGAT in response to pain. Results of the study showed that animals treated with gene-therapy showed a progressive loss of pain response 7 days after treatment, but returned to completely normal, pre-injury level pain responses 14 days after treatment. The researchers further determined that neurons normally associated with neuropathic pain became absent in 37% of neurons that underwent gene-therapy.
These results suggest that gene-therapy using GAD65 and VGAT may be a successful approach to reversing chronic neuropathic pain after spinal cord injury. Not only did the study demonstrate the improvement of pain following treatment, but pain-inducing neurons themselves were also found to be less active. While human trials are still necessary to confirm its effectiveness, this gene-therapy suggests a promising future for the treatment of SCI.
Tadokoro T, Bravo-Hernandez M, Agashkov K, et al. Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain. Molecular Therapy. (May 2022).