Relations Between Autophagy Dysregulation and Neuronal Degeneration in the Molecular Mechanisms of Neuropathic Pain

Abstract

Neuropathic pain is a chronic pain condition resulting from injury or dysfunction in the somatosensory nervous system, characterized by spontaneous pain, hyperalgesia, and allodynia. Recent research has highlighted the role of autophagy, a cellular degradation and recycling process, in maintaining neuronal homeostasis and preventing degeneration. However, in the context of neuropathic pain, dysregulation of autophagy can exacerbate neuronal damage and contribute to pain persistence. Autophagy plays a dual role in neuronal health, acting as a protective mechanism that clears damaged organelles and protein aggregates under physiological conditions but potentially contributing to neuronal injury when excessively activated or impaired. Key molecular pathways, such as the mTOR (mechanistic target of rapamycin) pathway, AMPK (AMP-activated protein kinase), and the autophagy-related (ATG) proteins, regulate autophagy and are altered in response to nerve injury. The failure to maintain proper autophagic flux can lead to the accumulation of damaged mitochondria, increased oxidative stress, and activation of apoptotic pathways, which further drive neuronal degeneration and pain. This review examines the interplay between autophagy dysregulation and neuronal degeneration in neuropathic pain, focusing on the molecular mechanisms that underlie these processes. We also discuss the potential of targeting autophagy pathways to mitigate neuronal injury and alleviate chronic pain. Understanding the role of autophagy in neuropathic pain may provide insights into novel therapeutic strategies for enhancing neuronal resilience and reducing the burden of chronic pain.