Chronic pain is repetitive or continuous and persists way beyond an acceptable period. The pain hinders day-to-day activities, affecting the quality of life. Biologically, pain can be defined as a warning mechanism in opposition to a harmful stimulus. Chronic pain can thus be explained as a prolonged response despite removing the stimuli. The condition may be related to a previous trauma, treatment, or disease.
In the world where millions of individuals battle the relentless burden of chronic pain, a glimmer of hope emerges from the forefront of medical sciences. Chronic pain, an affliction that affects the lives of countless people, often defies conventional treatments and leaves its sufferers in a state of constant anguish. However, recent advances in the field of gene therapy have ignited a beacon of optimism for those grappling with this unrelenting torment.
Oxycodone model and chronic pain
A systematic review published in June 2023 used an Oxycodone model to identify several drug targets for chronic pain. Variable expression profiles in several genes were identified in the Oxycodone model. However, the first genetic study for chronic pain was conducted by Nuffield Department of Clinical Neurosciences, Oxford. From the gene pool of 1,000 participants, a variant of the sodium-calcium exchanger gene NCX3 experiences pain more frequently and to a greater degree. Successive studies on mice showed that localization of NCX3 in spinal neurons was associated with higher pain sensitivity. Scientists concluded that NCX3 activating compounds may suppress pain sensitization.
OxyContin, Vicodin, morphine, and methadone are the most prescribed drugs for chronic pain. However, these drugs use opioids as their active ingredient. Opioids are a form of narcotics, and despite their excellent pain suppressive potential, the misuse of these opioid-based prescriptions has proven to be a major concern for the healthcare system. According to data collected by the World Health Organization (WHO), In 2019, of the 600,000 drug abuse-related deaths, 35% were due to opioid prescription.
CRISPR and its emergence in gene therapy
Sodium channels have since been thoroughly studied due to their role in the transmission of pain. More recent studies focus on NaV1.7 sodium ion channel related genes. Individuals with a particular variant of the NaV1.7 gene allow an abnormal inflow of sodium ions. On the other hand, genetic disruption of NaV1.7 is often associated with a complete lack of pain. Navega Therapeutics used CRISPR gene editing technology and zinc finger motifs to directly inactivate NaV1.7 genes but faced the problem of complete shutdown or off-target inactivation.
CRMP2 is a regulatory protein that interacts with NaV1.7 and modulates the flow of sodium ions. Controlling CRMP2 was the key to manage chronic pain. Scientists at the National Academy of Sciences, New York University, conducted research on the same. “We found a way to take an engineered virus, containing a small piece of genetic material from a protein that all of us have, and infect neurons to effectively treat pain,” explained a researcher. They developed a peptide sequence that, on binding with CRMP2, blocks its interaction with NaV1.7. The genetic material was transfected into the neurons via an adenoviral vector. The same scientists also explored mutation at the binding region of CRMP2 as a potential approach. Despite the promising preclinical results, in-silico studies posed the question of non-target binding and associated complications.
While concluding this, gene therapy holds immense promise as a groundbreaking approach to managing chronic pain. While the field is still in its early stages, the potential for long-lasting relief and improved quality of life for those suffering from chronic pain is undeniable. As researchers continue to unravel the complexities of gene therapy and refine its techniques, it can be anticipated that the future where chronic pain is not just managed but effectively treated.
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Carae Wagner specializes in reporting on the healthcare sector, with a specific emphasis on digital health, gene therapy, viral vectors, and public policy. She holds degrees in English and Psychology from the University of Virginia. Her writing has been featured in publications such as Forbes, Slate, C-Ville Weekly, and various others. She maintains a focus on anxiety disorders and depression and aims to explore other areas of mental health including dissociative disorders such as maladaptive daydreaming.