Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
12.4
6.6
Journals
Antioxidants
Special Issues
Chronic Pain and Oxidative Stress
share announcement

Chronic Pain and Oxidative Stress

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 11520

Special Issue Editor

Dr. Olga Pol

E-Mail Website
Guest Editor
Grup de Neurofarmacologia Molecular, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
Interests: analgesia; anxiety; depression; cannabinoids; carbon monoxide; heme oxygenase 1; hydrogen sulfide; molecular hydrogen; nitric oxide; Nrf2 transcription factor; oxidative stress; pain; opioids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic pain affects a high percentage of the population, making it a serious global health problem. Current therapies are ineffective and have significant side effects, negatively affecting the patients' quality of life.  Research into new treatments capable of effectively relieving chronic pain with few adverse effects constitutes a major challenge.

Oxidative stress and inflammation are two of the main mechanisms involved in the development of chronic pain, both of which can lead to mitochondrial dysfunction. Moreover, oxidative stress can activate redox-sensitive inflammatory mediators, causing uncontrolled inflammatory reactions that heighten pain sensitivity. Further studies are needed to clarify the molecular mechanisms involved in this process to identify new compounds as potential therapeutic targets for chronic pain.

The antioxidant system activated by the Nrf2 transcription factor serves as an endogenous defense mechanism against oxidative stress by reducing ROS levels, inflammatory responses, and mitochondrial impairment. The analgesic properties of several Nrf2-inducing compounds, such as sulforaphane and oltipraz, have been identified in various preclinical models of inflammatory and neuropathic pain. However, there is a wide range of antioxidant compounds whose analgesic properties and mechanisms of action have yet to be identified. This Special Issue titled "Chronic Pain and Oxidative Stress" aims to compile original research articles that evaluate the analgesic properties of novel compounds and their effects on oxidative stress, proinflammatory signals, and plasticity changes caused by inflammation, nerve injury, chemotherapeutic agents, and/or metabolic disorders. We believe this Special Issue will advance research into new, effective, and safe strategies for treating chronic pain that can be used in clinical practice.

As the Guest Editor, I invite you to contribute to this Special Issue.

I look forward to your contributions.

Dr. Olga Pol
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • analgesia
  • antioxidants
  • chemotherapy
  • heme oxygenase 1
  • neuropathy
  • nociception
  • Nrf2 transcription factor
  • oxidative stress
  • pain

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

17 pages, 1674 KB  
Article
DRG Explant Model for Understanding Mechanism of Oxaliplatin-Induced Peripheral Neuropathy and Identifying Potential Therapeutic Targets
by Junwei Du, Leland C. Sudlow, Igor D. Luzhansky and Mikhail Y. Berezin
Antioxidants 2026, 15(2), 230; https://doi.org/10.3390/antiox15020230 - 10 Feb 2026
Cited by 1 | Viewed by 1012
Abstract
Oxaliplatin-triggered chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment that limits the efficacy of chemotherapy and negatively impacts patients’ quality of life dramatically. To better understand the mechanisms of CIPN and to screen for potential therapeutic targets, [...] Read more.
Oxaliplatin-triggered chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment that limits the efficacy of chemotherapy and negatively impacts patients’ quality of life dramatically. To better understand the mechanisms of CIPN and to screen for potential therapeutic targets, it is critical to have reliable in vitro assays that effectively mirror the neuropathy in vivo. In this study, we established a dorsal root ganglia (DRG) explant model. This model displayed dose-dependent inhibition of neurite outgrowth in response to oxaliplatin, while oxalic acid exhibited no significant impact on the regrowth of DRG. The robustness of this assay was further demonstrated by the inhibition of OCT2 transporter, which facilitates oxaliplatin accumulation in neurons, largely restoring the neurite regrowth capacity. Using this model, we revealed that oxaliplatin triggered a substantial increase of oxidative stress in DRG. Notably, inhibition of TXNIP with verapamil reduced oxidative stress levels. Our results demonstrated the use of DRG explants as an efficient model to study the mechanisms of CIPN and screen for potential treatments. Full article
(This article belongs to the Special Issue Chronic Pain and Oxidative Stress)
►▼ Show Figures

Graphical abstract

25 pages, 2932 KB  
Article
Pain Hypersensitivity in a Mouse Model of Marfan Syndrome
by Rebecca Kordikowski, Joana Coutinho, Ignacio Martínez-Martel, Clara Penas, Beatriz Martín-Mur, Belén Pérez, Francesc Jiménez-Altayó and Olga Pol
Antioxidants 2026, 15(1), 80; https://doi.org/10.3390/antiox15010080 - 8 Jan 2026
Viewed by 1134
Abstract
Marfan syndrome (MFS) is a genetic disorder caused by mutations in the fibrillin-1 (Fbn1) gene, leading to structurally abnormal elastic fibers and diverse clinical manifestations. Aortic root dilation represents the most serious threat, often requiring prophylactic surgical repair. Emerging evidence suggests that MFS [...] Read more.
Marfan syndrome (MFS) is a genetic disorder caused by mutations in the fibrillin-1 (Fbn1) gene, leading to structurally abnormal elastic fibers and diverse clinical manifestations. Aortic root dilation represents the most serious threat, often requiring prophylactic surgical repair. Emerging evidence suggests that MFS patients experience increased pain sensitivity, contributing to functional impairment and reduced quality of life. Here, we used C57BL/6 wild-type and Fbn1C1041G/+ (MFS) mice to examine brain transcriptomics, aortic histology, nociceptive behaviors, grip strength, and spinal cord gene expression in both sexes at 2, 4, 6, 8, and 16 months of age. Transcriptomic analysis revealed reduced activation of pain-related pathways in young males and aged females, with a reversal in aged males, suggesting age- and sex-dependent differences in pain modulation. Behavioral testing showed progressive mechanical and thermal hypersensitivity in MFS mice, with cold allodynia as the earliest manifestation with late-onset muscle weakness. In the spinal cord of 16-month-old MFS mice, increased expression of key excitatory and nociceptive markers was observed, consistent with the pain hypersensitivity phenotype. In addition, aged female MFS mice exhibited elevated spinal expression of pro-inflammatory cytokines, inducible nitric oxide synthase, and Nox4, whereas males showed increased transforming growth factor-β1 and Nox1, reflecting distinct inflammatory and oxidative stress profiles. These findings demonstrate that Fbn1C1041G/+ mice reproduce pain hypersensitivity and muscle deficits observed in MFS patients, supporting their use as a preclinical model. Our results suggest that enhanced spinal excitatory/nociceptive signaling, together with neuroinflammation and oxidative stress, contributes to sex- and age-specific pain mechanisms in MFS. Full article
(This article belongs to the Special Issue Chronic Pain and Oxidative Stress)
►▼ Show Figures

Figure 1

Review

Jump to: Research

34 pages, 3231 KB  
Review
Targeting Oxidative Stress and Mitochondrial Dysfunction in Diabetic Neuropathy: Mechanisms and Therapeutic Opportunities
by Ferenc Sztanek, László Imre Tóth, Marcell Hernyák, Attila Pető, Hajnalka Lőrincz, Adrienn Menyhárt, Dóra Marietta Balogh, Attila Csaba Nagy, Peter Kempler, György Paragh and Mariann Harangi
Antioxidants 2026, 15(3), 367; https://doi.org/10.3390/antiox15030367 - 13 Mar 2026
Viewed by 1836
Abstract
Diabetic neuropathy is a frequent and disabling complication of diabetes, encompassing distal symmetric polyneuropathy and cardiovascular autonomic neuropathy, both associated with reduced quality of life and increased cardiovascular risk. Beyond its traditional interpretation as a direct consequence of chronic hyperglycaemia, oxidative stress has [...] Read more.
Diabetic neuropathy is a frequent and disabling complication of diabetes, encompassing distal symmetric polyneuropathy and cardiovascular autonomic neuropathy, both associated with reduced quality of life and increased cardiovascular risk. Beyond its traditional interpretation as a direct consequence of chronic hyperglycaemia, oxidative stress has emerged as a central integrative mechanism linking metabolic overload, inflammation, mitochondrial dysfunction, and microvascular injury to progressive neural damage. These processes converge within the neurovascular unit, promoting a self-perpetuating cycle of axonal degeneration, impaired nerve perfusion and altered neuronal excitability. This narrative review synthesises experimental and clinical evidence on oxidative stress-related pathways implicated in diabetic neuropathy, including hyperglycaemia-activated metabolic routes, mitochondrial dysfunction, endoplasmic reticulum stress, and chronic inflammatory signalling. Classical antioxidant and mitochondrial-supportive interventions are evaluated alongside pleiotropic glucose-lowering agents, with particular emphasis on sodium–glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, integrating mechanistic insights with biomarker and clinical outcome data. Conventional antioxidant strategies, such as α-lipoic acid, acetyl-L-carnitine, coenzyme Q10 and N-acetylcysteine, show reproducible benefits on neuropathic symptoms and oxidative stress markers, but evidence for sustained structural or disease-modifying effects remains limited. In contrast, incretin-based therapies and sodium–glucose cotransporter-2 inhibitors exert broader pleiotropic actions by attenuating oxidative and inflammatory signalling, improving mitochondrial homeostasis and endothelial function, with emerging evidence for modest but consistent neurophysiological and autonomic benefits. Overall, oxidative stress emerges as a key mechanistic hub in diabetic neuropathy. Future progress will depend on mechanism-aligned, neuropathy-specific clinical trials incorporating multidimensional endpoints and validated biomarkers. Full article
(This article belongs to the Special Issue Chronic Pain and Oxidative Stress)
►▼ Show Figures

Graphical abstract

22 pages, 1344 KB  
Review
Fibromyalgia, Eating Disorders and Rehabilitation: The Nrf2 Link
by Roberto Casale, Paolo Capodaglio, Kestutis Petrikonis, Antonella Paladini, Piercarlo Sarzi-Puttini and Jurga Bernatoniene
Antioxidants 2026, 15(3), 364; https://doi.org/10.3390/antiox15030364 - 12 Mar 2026
Viewed by 1362
Abstract
Background: Fibromyalgia (FM) and eating disorders (ED) represent distinct clinical entities traditionally managed within separate medical specialties, yet emerging evidence suggests significant comorbidity and potential shared pathophysiological mechanisms. Both conditions disproportionately affect women, involve complex multifactorial etiologies and substantially impair quality of life. [...] Read more.
Background: Fibromyalgia (FM) and eating disorders (ED) represent distinct clinical entities traditionally managed within separate medical specialties, yet emerging evidence suggests significant comorbidity and potential shared pathophysiological mechanisms. Both conditions disproportionately affect women, involve complex multifactorial etiologies and substantially impair quality of life. Despite documented clinical overlaps, the mechanistic connections linking these conditions remain poorly characterized, and integrated treatment approaches are lacking. Objective: This narrative review examines the role of oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway dysfunction as a unifying molecular mechanism connecting fibromyalgia and eating disorders, with emphasis on implications for integrated rehabilitation strategies. Methods: We synthesized current evidence on oxidative stress pathophysiology in fibromyalgia and eating disorders, focusing on Nrf2-Keap1 pathway function, clinical comorbidity patterns and rehabilitation interventions targeting antioxidant defense mechanisms. In PubMed, representative search strings included “(fibromyalgia [MeSH] OR fibromyalgia [Title/Abstract]) AND (“eating disorders” [MeSH] OR “anorexia nervosa” [MeSH] OR “bulimia nervosa” [MeSH])” and “fibromyalgia AND (“oxidative stress” OR Nrf2 OR “redox”)”. Articles in English published through December 2025 were considered, with additional records identified by manually screening reference lists. Results: Fibromyalgia patients exhibit elevated oxidative stress markers, impaired antioxidant enzyme function and compromised Nrf2 activity correlating with disease severity, with studies reporting approximately 30–50% reductions in coenzyme Q10 levels compared with healthy controls. Similarly, eating disorders demonstrate mitochondrial dysfunction and oxidative stress dysregulation, though patterns differ across eating disorder phenotypes. Nrf2 serves as the master regulator of cellular antioxidant defense, coordinating expression of over 500 genes involved in detoxification, cytoprotection, inflammation modulation and metabolic regulation. Evidence suggests Nrf2 activity is regulated by energy balance, potentially linking nutritional status with cellular stress responses. Rehabilitation interventions, including graduated exercise and nutritional optimization with Nrf2-activating foods (cruciferous vegetables, polyphenols, omega-3 fatty acids), offer mechanism-based therapeutic approaches through hormetic Nrf2 activation and direct Keap1 modification. Conclusions: Multidisciplinary rehabilitation programs integrating physical therapy, exercise prescription and nutritional strategies targeting Nrf2 activation offer evidence-based, mechanism-driven approaches to address shared oxidative stress pathophysiology. Nrf2 pathway dysfunction represents a promising and biologically plausible molecular target that may help to unify our understanding of fibromyalgia and eating disorders pending confirmation from prospective clinical studies in comorbid populations. Future research should prioritize prospective clinical trials testing Nrf2-targeted interventions in comorbid populations and collaborative patient-centered care models. Full article
(This article belongs to the Special Issue Chronic Pain and Oxidative Stress)
►▼ Show Figures

Graphical abstract

44 pages, 9564 KB  
Review
Oxidative Stress, Inflammation, and Cellular Senescence in Neuropathic Pain: Mechanistic Crosstalk
by Bojan Stojanovic, Ivana Milivojcevic Bevc, Milica Dimitrijevic Stojanovic, Bojana S. Stojanovic, Tatjana Lazarevic, Marko Spasic, Marko Petrovic, Ivana Stefanovic, Marina Markovic, Jelena Nesic, Danijela Jovanovic, Miodrag Peulic, Ana Azanjac Arsic, Ana Lukovic, Nikola Mirkovic, Stevan Eric and Nenad Zornic
Antioxidants 2025, 14(10), 1166; https://doi.org/10.3390/antiox14101166 - 25 Sep 2025
Cited by 19 | Viewed by 5179
Abstract
Neuropathic pain is a chronic condition driven by intertwined mechanisms of oxidative stress, inflammation, and cellular senescence. Nerve injury and metabolic stress elevate reactive oxygen and nitrogen species, disrupt mitochondrial function, and activate the DNA-damage response, which stabilizes p53 and induces p16/p21-mediated cell-cycle [...] Read more.
Neuropathic pain is a chronic condition driven by intertwined mechanisms of oxidative stress, inflammation, and cellular senescence. Nerve injury and metabolic stress elevate reactive oxygen and nitrogen species, disrupt mitochondrial function, and activate the DNA-damage response, which stabilizes p53 and induces p16/p21-mediated cell-cycle arrest. These events promote a senescence-associated secretory phenotype (SASP) rich in cytokines, chemokines, and prostanoids that amplify neuroimmune signaling. In the spinal dorsal horn and dorsal root ganglia, microglia and astroglia respond to redox imbalance and danger cues by engaging NF-κB and MAPK pathways, increasing COX-2–dependent prostaglandin synthesis, and releasing mediators such as IL-1β and BDNF that enhance synaptic transmission and reduce inhibitory tone through KCC2 dysfunction. At the periphery, persistent immune-glial cross-talk lowers activation thresholds of nociceptors and sustains ectopic firing, while impaired autophagy and mitophagy further exacerbate mitochondrial dysfunction and ROS production. Collectively, these processes establish a feed-forward loop in which redox imbalance triggers senescence programs and SASP, SASP perpetuates neuroinflammation, and neuroinflammation maintains central sensitization—thereby consolidating a self-sustaining redox–senescence–inflammatory circuit underlying neuropathic pain chronicity. Full article
(This article belongs to the Special Issue Chronic Pain and Oxidative Stress)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop