Genetic modulation of pain pathways: toward a new era in pain therapy- a systematic review
Clinical Snapshot
PICO Framework
| P — Population | Patients with chronic pain conditions including neuropathy, arthritis, fibromyalgia, and complex regional pain syndrome |
| I — Intervention | Gene therapy approaches including RNA interference (RNAi), viral vector delivery, CRISPR/Cas9, gene replacement therapy, and endogenous opioid gene delivery |
| C — Comparator | Standard pain management approaches or control groups in included studies |
| O — Outcomes | Pain reduction, quality of life improvement, safety profiles, and mechanisms of action in pain modulation |
Bottom Line
This systematic review examines gene therapy approaches for chronic pain management, identifying 18 studies from preclinical research. While RNA interference, CRISPR/Cas9, and viral vector delivery systems show promise for targeting pain pathways directly, the evidence remains predominantly experimental. Safety concerns, particularly with CRISPR technology, and the early-stage nature of research limit immediate clinical translation. The review lacks quantitative synthesis and detailed quality assessment, reducing confidence in findings. For Australian clinicians, these approaches remain investigational and would require extensive regulatory approval before clinical implementation. Current evidence is insufficient to change practice, but the field represents a potentially transformative approach to chronic pain management that warrants continued research investment and monitoring.
Key Findings
P Value: Not applicable for systematic review without meta-analysis
Effect Size: Not quantified - qualitative synthesis only
Primary Outcome: Gene therapy modalities showed promise for pain reduction across multiple conditions
Nnt Or Sensitivity: Not calculated - insufficient data for clinical translation
Confidence Interval: Not reported
Clinical Application
Low feasibility for immediate clinical use due to safety concerns and regulatory requirements Would require TGA approval for clinical trials. Not covered under PBS. Significant regulatory and ethical considerations for gene therapy applications Currently limited to research settings - not ready for clinical application
Abstract
Gene therapy represents a new strategy in pain management targeting the causes of pain rather than its symptoms. This review summarizes recent advances across RNA interference (RNAi), viral vector delivery systems, CRISPR/Cas9, gene replacement therapy, and endogenous opioid gene delivery, emphasizing efficacy, safety, and mechanisms of action in pain conditions. RNAi and gene replacement techniques remain powerful tools for reducing pain and improving the quality of life by modulating pain-associated genes. Long-term relief may also be achieved with CRISPR/Cas9 and site-directed delivery using nanoparticle systems. Safety profiles especially with CRISPR/Cas9 remains a concern. A systematic search of Web of Science, Medline, Scopus, and Google Scholar identified 512 records (January 2010-March 2023). Following PRISMA screening, 18 studies met inclusion criteria. These studies evaluated strategies of gene therapy in neuropathy, arthritis, fibromyalgia, and complex regional pain syndrome. The review outlines available options and highlights preclinical findings.
References
- 1.Jaffal, S., & Jaffal, G. (2026). Genetic modulation of pain pathways: toward a new era in pain therapy- a systematic review. Molecular Biology Reports. https://doi.org/10.1016/j.xcrm.2024.101756
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