AD16 as a novel therapeutic agent: Mechanisms and efficacy in chronic inflammatory pain management

Chronic inflammatory pain is a complex condition marked by enduring pain due to inflammation and central sensitization. Present therapeutic strategies primarily rely on non-steroidal anti-inflammatory drugs (NSAIDs) or opioid-based treatments, which frequently entail considerable adverse effects and demonstrate limited efficacy in managing chronic pain. Therefore, there is a pressing need to identify novel therapeutic strategies that can effectively target and modulate the underlying mechanisms of chronic inflammatory pain. Here, we examined an innovation compound named AD16 in mitigating chronic inflammatory pain and investigated its molecular mechanisms. The findings revealed that AD16 significantly attenuated pain-related behaviors in rat models of chronic inflammatory pain induced by complete Freund's adjuvant (CFA), specifically reducing foot swelling and mechanical allodynia. AD16 was found to be associated with the activation of GABA_B receptors and alterations in the expression ratios of GluN2A/GluN2B subunits, suggesting a potential impact on synaptic plasticity. Furthermore, AD16 was correlated with a reduction in systemic inflammatory markers, as demonstrated by decreased levels of IL-1β and increased levels of IL-10 known to play roles in the modulation of central sensitization in inflammatory pain. These findings suggest that AD16 may counteract CFA-induced central sensitization by restoring two critical pathways: (1) the balance between neuronal excitation and inhibition, and (2) the equilibrium between pro-inflammatory and anti-inflammatory immune responses within the spinal cord. Consequently, AD16 represents a promising therapeutic candidate for chronic inflammatory pain.