The multifaceted role of cofilin in inflammation and pain signaling

This review aims to explore the pivotal role of cofilin a major regulator of actin cytoskeleton remodelling in linking inflammation and neuropathic pain. By examining molecular pathways and cellular mechanisms, this review explores how cofilin influences immune responses and contributes to the development and persistence of neuropathic pain. Cofilin mediates T-cell activation and migration through dynamic actin turnover at the immune synapse, governed by upstream regulators such as Ras, PI3K, and PLC. Its redox-sensitive modulation, nuclear translocation, and transcriptional control further contribute to inflammatory processes. In neuropathic pain, the RhoA/LIMK/cofilin pathway is activated following nerve injury, leading to abnormal actin dynamics and hyperalgesia. Cofilin is implicated in ROS production, mitochondrial apoptosis, and actin-cofilin rod formation, all of which together, disrupt cellular homeostasis in neurodegeneration. Experimental models of traumatic brain injury (TBI) and spared nerve injury (SNI) have confirmed cofilin’s role in microglial activation and emotional dysfunction associated with chronic pain. The multifunctional roles of cofilin in cytoskeletal remodelling and inflammatory signaling make it a promising therapeutic target for treating neuroinflammation and neuropathic pain. Techniques including small-molecule inhibitors, gene modulation, and combination therapies with iron chelators or anti-inflammatory agents warrant further exploration in preclinical and clinical research.