The Effect of Super-Repressor IkB-Loaded Exosomes (Exo-srIκBs) in Chronic Post-Ischemia Pain (CPIP) Models

Abstract

Complex regional pain syndrome (CRPS) is a condition associated with neuropathic pain that causes significant impairment of daily activities and functioning. Nuclear factor kappa B (NFκB) is thought to play an important role in the mechanism of CRPS. Recently, exosomes loaded with super-repressor inhibitory kappa B (Exo-srIκB, IκB; inhibitor of NFκB) have been shown to have potential anti-inflammatory effects in various inflammatory disease models. We investigated the therapeutic effect of Exo-srIκB on a rodent model with chronic post-ischemia pain (CPIP), a representative animal model of Type I CRPS. After intraperitoneal injection of a vehicle, Exo-srIκB, and pregabalin, the paw withdrawal threshold (PWT) was evaluated up to 48 h. Administration of Exo-srIκB increased PWT compared to the vehicle and pregabalin, and the relative densities of p-IκB and IκB showed significant changes compared to the vehicle 24 h after Exo-srIκB injection. The levels of several cytokines and chemokines were reduced by the administration of Exo-srIκB in mice with CPIP. In conclusion, our results showed more specifically the role of NFκB in the pathogenesis of CRPS and provided a theoretical background for novel treatment options for CRPS.

Efficacy of Allogeneic and Xenogeneic Exosomes for the Treatment of Canine Atopic Dermatitis: A Pilot Study

“…These are human embryonic kidney cell lines that are easy to manipulate and show high growth capacity; therefore, they are commonly used to produce therapeutic proteins or exosomes in human medicine [33,58]. We used the engineered exosome loaded with srIκB, a nondegradable form of IκB that prevents the nuclear translocation of NFκB [59]. NFκB is one of the most important regulators of proinflammatory gene expression and is highly activated at sites of inflammation in diverse diseases [60].…”

Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications

“…[ 226 ] treated post-ischemic mice with srIκB-loaded exosomes to suppress the NF-κB signaling cascade activated during kidney ischemia–reperfusion injury. Recently, these srIκB-loaded exosomes were also employed to suppress inflammation in models of alcohol-associated liver disease [ 227 ] and neuropathic pain [ 228 ].…”

The Role of Neuroinflammation in Complex Regional Pain Syndrome: A Comprehensive Review

“…56 Animal studies have yielded similar findings, as demonstrated by a significant upregulation of proinflammatory mediators and chemokines in the plantar, spinal dorsal horn (SDH), and DRG of rats in the chronic post-ischemia pain (CPIP) model of CRPS. [57][58][59] Furthermore, upregulation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome expression has been observed in the spinal dorsal horn of rats with CPIP. Inflammasomes play a crucial role in the occurrence and development of cytokine-mediated chronic pain, with proinflammatory cytokines IL-1β and IL-18 being the primary products of neutrophilic alkaline phosphatase (NALP) 1 and NLRP3 inflammasomes.…”