Stress/cell death pathways, neuroinflammation, and neuropathic pain

Abstract

SummaryNeuropathic pain is a common and debilitating modality of chronic pain induced by a lesion or disease of the somatosensory nervous system. Albeit the elucidation of numerous pathophysiological mechanisms and the development of potential treatment compounds, safe and reliable therapies of neuropathic pain remain poor. Multiple stress/cell death pathways have been shown to be implicated in neuroinflammation during neuropathic pain. Here, we summarize the current knowledge of stress/cell death pathways and present an overview of the roles and molecular mechanisms of stress/cell death pathways in neuroinflammation during neuropathic pain, covering intrinsic and extrinsic apoptosis, autophagy, mitophagy, ferroptosis, pyroptosis, necroptosis, and phagoptosis. Small molecule compounds that modulate stress/cell death pathways in alleviating neuropathic pain are discussed mainly based on preclinical neuropathic pain models. These findings will contribute to in‐depth understanding of the pathological processes during neuropathic pain as well as bridge the gap between basic and translational research to uncover new neuroprotective interventions.

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

“…It causes degradation of cytoplasmic proteins and other macromolecules within the lysosome in multicellular organisms [71]. It has been demonstrated to be involved in neuroinflammation and ND, which are characterized by protein aggregation and exacerbated autophagy [72][73][74]. However, the mechanisms involved are not clear [75][76][77].…”

Mitochondrial Dysfunction and Disulfidptosis Co-regulate Neuronal cell in Neuropathic Pain Based on Bioinformatics Analysis

“…Mitochondria also play a crucial role in regulating various forms of cell death, including necroptosis, ferroptosis, and pyroptosis (Bock & Tait 2020). Studies have indicated that neuroimmune mechanisms involved in neuropathic pain may be associated with multiple forms of cell death, such as necroptosis, pyroptosis, and ferroptosis (Bi et L. Li et al 2024). Investigating the role of mitochondrial dysfunction and disul dptosis in neuropathic pain could provide insights for the development of improved therapeutic strategies.…”

Cell type‐specific molecular mechanisms and implications of necroptosis in inflammatory respiratory diseases

“…Cell death is fundamental for the development and homeostasis of organisms 1–3 . Necroptosis is a caspase‐independent modality of programmed cell death (PCD), which was first proposed by Degterev in 2005 4,5 .…”

“…Cell death is fundamental for the development and homeostasis of organisms. [1][2][3] Necroptosis is a caspase-independent modality of programmed cell death (PCD), which was first proposed by Degterev in 2005. 4,5 Necroptosis can be initiated by death receptors and pathogen receptors, involving clumping dying cells, rupture of cell membrane, swelling of cell bodies and organelles, and inflammasome formation.…”