Delivery of Nerve Growth Factor via Exosome Attenuates Neuropathic Pain in a Rat Model of Chronic Constriction Injury

Introduction: The nerve growth factor (NGF) is a crucial neurotrophic factor with the ability to induce neuronal differentiation. However, whether NGF-loaded exosomes (Exo-NGF) can alleviate neuropathic pain in chronic constriction injury (CCI) rats remains unclear. Methods: A neuropathic pain model was established using CCI rats. The pain was assessed using the von Frey test and the hot plate test. Exo-NGF was collected from HEK293 cells transfected with an NGF plasmid. The diameter of Exo-NGF was determined using transmission electron microscopy. Protein levels of inflammatory factors, including IL-18, IL-1β, and TNF-α, were measured using enzyme- linked immunosorbent assay, and their mRNA levels were evaluated using qPCR. The NODlike receptor family pyrin domain-containing protein 3 (NLRP3) protein levels were determined using immunostaining and Western blot. Results: NGF protein and mRNA were highly expressed in Exo-NGF. The mRNA in Exo-NGF was successfully delivered into neural stem cells and promoted their differentiation. Injection of Exo- NGF into the spinal dorsal horn significantly alleviated mechanical allodynia and thermal hyperalgesia. Additionally, Exo-NGF reduced levels of IL-18, IL-1β, and TNF-α. NLRP3 and its key components, including apoptosis-associated speck-like protein and caspase-1, were also reduced by Exo- NGF treatment in CCI rats. Discussion: Our findings highlight the therapeutic potential of exosome-based NGF delivery for treating chronic pain conditions. Conclusion: Exo-NGF significantly alleviates neuropathic pain by suppressing inflammation and NLRP3 activation.