Redox Stress, Mitochondrial Dysfunction, and Regulated Cell Death Mechanisms in Neuropathic Pain

The field of neuropathic pain research has increasingly turned its attention toward the intricate interplay between redox homeostasis, mitochondrial function, and regulated cell-death pathways. Although early studies focused on neuronal excitability and neuroimmune crosstalk, more recent evidence demonstrates that redox imbalance, mitochondrial dysfunction, and aberrant cell-death mechanisms play pivotal roles in pain chronification. Redox stress can drive persistent lipid peroxidation and disturbances in iron metabolism, which, together with impaired mitophagy, have been implicated in heightened pain sensitivity across animal and translational human models. Despite notable progress, much remains to be learned about how these cellular stress responses are coordinated, particularly regarding their integration with neuron-glia interactions, ion channel function, and inflammatory signaling driven by danger-associated molecular patterns (DAMPs).

This Research Topic aims to clarify the molecular relationships that connect oxidative stress, mitochondrial dysfunction—including mitochondrial dynamics and quality control processes such as mitophagy and autophagy—and regulated cell-death mechanisms in neuropathic pain. A central objective is to define how failure of mitochondrial quality control and redox homeostasis triggers cell death programs (such as ferroptosis, apoptosis, necroptosis, and pyroptosis) and DAMP-mediated inflammatory signaling, which together may sustain or exacerbate pain states. Emphasis will be placed on mechanistic investigations that illuminate novel molecular targets or biomarkers, with a particular focus on those aspects identified as most impactful by ongoing studies and emerging clinical data.

The scope of this Research Topic is limited to investigations exploring neuropathic pain through the central axes of oxidative/mitochondrial stress, mitochondrial dynamics and quality control, and regulated cell death. Broader neurobiological themes should be included only when they are directly linked to these mechanisms. To gather further insights in this focused area, we welcome articles addressing, but not limited to, the following themes:

o Mechanistic studies of redox imbalance and lipid peroxidation in neuropathic pain models

o Roles of iron metabolism dysregulation and ferroptosis in pain development and maintenance

o Mitochondrial dysfunction, dynamics, and quality control (including mitophagy/autophagy) as drivers or moderators of pain sensitivity

o Interactions between oxidative/mitochondrial stress and DAMPs or inflammasome activation

o Regulated cell-death programs (ferroptosis, apoptosis, necroptosis, pyroptosis) as determinants of neuron and glial cell survival and pain persistence

o Ion channel or transporter modulation specifically in the context of redox or mitochondrial stress

o Epigenetic or transcriptional signaling as downstream consequences of oxidative/mitochondrial dysfunction

o Biomarker or therapeutic target discovery centered on redox or mitochondrial pathways

o Disease models, such as traumatic nerve injury, diabetic neuropathy, chemotherapy-induced neuropathy, post-ischemic or central neuropathic pain, provided the core mechanistic axis involves redox/mitochondrial stress or regulated cell death

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: neuropathic pain, oxidative stress, mitochondrial dysfunction, regulated cell death, ferroptosis, mitophagy

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.