The Impact of Axonal Transport Disruption and Cytoskeletal Alterations on Neuronal Integrity in the Context of Neuropathic Pain
Ioana Marinescu
Vladimir Kovačević
Abstract
Neuropathic arises from injury or dysfunction of the somatosensory nervous system, characterized by persistent pain, hyperalgesia, and allodynia. A critical aspect of neuropathic pain pathophysiology involves disruptions in axonal transport and alterations in the cytoskeleton, which impact neuronal integrity and contribute to ongoing pain. Axonal transport, the process that moves organelles, proteins, and signaling molecules along axons, is essential for maintaining neuronal function and connectivity. Following nerve injury, disruptions in axonal transport occur due to damage to microtubules, motor proteins like kinesin and dynein, and impairments in mitochondrial movement, leading to deficits in cellular energy and axonal degeneration. Cytoskeletal alterations, including changes in microtubules, neurofilaments, and actin filaments, further compromise axonal stability and structural integrity, exacerbating neuronal injury and promoting the degeneration of affected neurons. These disruptions contribute to the loss of synaptic connectivity, the induction of neuroinflammation, and the sensitization of pain pathways. This review examines the mechanisms through which axonal transport disruption and cytoskeletal alterations contribute to neuronal damage in neuropathic pain. We focus on key molecular players such as tau, MAP kinases, and signaling pathways like JNK that influence cytoskeletal dynamics and axonal transport. Additionally, we discuss potential therapeutic strategies aimed at stabilizing the cytoskeleton and improving axonal transport to preserve neuronal function and alleviate chronic pain. Understanding these processes is essential for developing new approaches to protect neuronal integrity and manage the progression of neuropathic pain.
