Dexmedetomidine-Loaded Hydrogel Microneedles Alleviate Acute Inflammatory Visceral Pain in Mice

Acute inflammatory visceral pain (AIVP) is a prevalent yet challenging clinical condition associated with inflammatory diseases, characterized by diffuse pain that often escalates into nausea, vomiting, and systemic autonomic disturbances. The absence of effective and patient-centered therapies remains a significant clinical challenge. While dexmedetomidine (Dex) has demonstrated promising analgesic effects, its conventional intravenous administration involves slow infusion, heightening risks of infection and compromising patient comfort and compliance. Here, we present a breakthrough strategy using a hyaluronic acid (HA) hydrogel and microneedle-based transdermal system for Dex delivery to enhance clinical practicality. We successfully fabricated Dex-loaded HA hydrogel microneedles (MN/Dex), enabling efficient skin penetration and controlled drug release. Comprehensive biosafety evaluations, including skin irritation, cytotoxicity, and hemolysis assays, confirmed the excellent biocompatibility of the HA hydrogel microneedle system (HA-MN). In the acetic-acid-induced AIVP model, MN/Dex not only produced significant and sustained reduction in visceral and somatic hyperalgesia but also maintained normal physiological activity, avoiding sedation burden, preserving feeding behavior, and supporting natural mobility. MN/Dex offers a minimally invasive, easy-to-administer, and well-tolerated alternative to intravenous therapy, with the potential to transform outpatient management and improve quality of life for patients suffering from AIVP. This advanced delivery platform bridges a critical translational gap in pain management, combining efficacy with outstanding clinical adaptability.