Nanoparticle and Gene Therapy Strategies for Site‐Specific Pain Management: A Review

Abstract Effective pain management, particularly following physical injury, remains a major clinical challenge due to the limitations of systemic analgesics, including opioids and nonsteroidal anti‐inflammatory drugs (NSAIDs), which often cause adverse effects and provide inadequate site‐specific relief. Emerging strategies that utilize nanoparticles and gene therapy offer promising alternatives by enabling localized delivery of analgesic agents directly to injured tissues. Nanocarriers such as liposomes, polymeric nanoparticles, and gold‐based systems facilitate targeted accumulation and controlled release of therapeutic agents, thereby enhancing efficacy while reducing systemic toxicity. Concurrently, gene therapy enables modulation of pain‐associated pathways through tissue‐specific expression or silencing of target genes, offering sustained and potentially long‐term analgesia. This review discusses the mechanisms, design principles, and recent advances in nanoparticle‐ and gene therapy‐based approaches for pain modulation. Preclinical models and early clinical investigations indicate the feasibility of these technologies in achieving targeted, prolonged pain relief. Key barriers to clinical translation, including delivery efficiency, immune compatibility, and regulatory considerations, are also addressed. Future directions highlight the integration of responsive nanomaterials, CRISPR‐based gene editing, and hybrid platforms as next‐generation solutions for personalized, site‐specific pain management.