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Antioxidants
Special Issues
Antioxidants in Chronic Pain
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Antioxidants in Chronic Pain

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: closed (30 January 2021) | Viewed by 12875

Special Issue Editor

Dr. Olga Pol

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

Special Issue Information

Dear Colleagues,

Chronic pain is a clinical challenge. Most patients with chronic pain do not respond well to the current therapies such as tricyclic antidepressants, nonsteroidal anti-inflammatory drugs, anticonvulsants or opioids. These treatments have low efficacy and numerous side effects, such as tolerance, respiratory depression, constipation, stomach ulcers, etc. Therefore, the investigation of new treatments capable of effectively relieving chronic pain is an important challenge in the therapy of pain.

Oxidative stress is one of the principal mechanisms involved in the development and maintenance of chronic pain contributing to the peripheral and central sensitization. Consequently, treatment with antioxidant compounds plays a protective role in neuropathic pain via activating the nuclear factor erythroid derived-2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathway and/or inhibiting the proinflammatory signals and the plasticity changes provoked by nerve injuries, chemotherapeutic agents or metabolic disorders, such as diabetes. These compounds also inhibit chronic inflammatory pain in many preclinical pain models by restoring the homeostatic equilibrium.

There is a wide variety of antioxidant compounds with different structure and chemical properties whose analgesic properties and mechanism of action during chronic pain have not been identified. This Special Issue on “Antioxidants in Chronic Pain” aims to collect original research papers designed to identify new antioxidant compounds able to efficiently relieve chronic pain, as potential therapeutic targets. We believe that this Special Issue will help toward advancing research on new effective strategies in the treatment of chronic pain.

We look forward to your contribution.

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 100 words) can be sent to the Editorial Office for announcement on this website.

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
  • Heme oxygenase 1
  • Neuropathy
  • Nociception
  • Nrf2 transcription factor
  • Oxidative stress
  • Pain

Published Papers (3 papers)

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Research

17 pages, 3713 KiB  
Article
The Antinociceptive, Antioxidant and Anti-Inflammatory Effects of 5-Fluoro-2-Oxindole during Inflammatory Pain
by Alejandro Redondo, Gabriela Riego and Olga Pol
Antioxidants 2020, 9(12), 1249; https://doi.org/10.3390/antiox9121249 - 09 Dec 2020
Cited by 9 | Viewed by 2134
Abstract
Recent studies demonstrate that 5-fluoro-2-oxindole inhibits neuropathic pain but the antinociceptive actions of this drug and its effects on the plasticity, oxidative and inflammatory changes induced by peripheral inflammation as well as on the effects and expression of µ-opioid receptors (MOR) have not [...] Read more.
Recent studies demonstrate that 5-fluoro-2-oxindole inhibits neuropathic pain but the antinociceptive actions of this drug and its effects on the plasticity, oxidative and inflammatory changes induced by peripheral inflammation as well as on the effects and expression of µ-opioid receptors (MOR) have not been evaluated. In C57BL/6 male mice with inflammatory pain provoked by the subplantar administration of complete Freund’s adjuvant (CFA), we evaluated: (1) the antinociceptive actions of 5-fluoro-2-oxindole and its reversion with the HO-1 inhibitor, tin protoporphyrin IX (SnPP); (2) the effects of 5-fluoro-2-oxindole in the protein levels of mitogen-activated protein kinase (MAPK), Nrf2, NADPH quinone oxidoreductase1 (NQO1), heme oxygenase 1 (HO-1), oxidative stress marker (4-hydroxy-2-nonenal; 4-HNE), inducible nitric oxide synthase (NOS2), microglial markers (CD11b/c and IBA-1), and MOR in the spinal cord and/or paw of animals with inflammatory pain; (3) the antinociceptive effects of morphine in 5-fluoro-2-oxindole pre-treated animals. Treatment with 5 and 10 mg/kg of 5-fluoro-2-oxindole inhibited the allodynia and hyperalgesia induced by CFA in a different, time-dependent manner. These effects were reversed by SnPP. Treatment with 5-fluoro-2-oxindole increased the expression of NQO1, HO-1 and MOR and inhibited the CFA-induced upregulation of phosphorylated MAPK, 4-HNE, NOS2, CD11b/c and IBA-1 in spinal cords and/or paws. The local effects of morphine were improved with 5-fluoro-2-oxindole. This work reveals that 5-fluoro-2-oxindole inhibits the plasticity, oxidative and inflammatory responses provoked by peripheral inflammation and potentiates the antinociceptive effects of morphine. Thus, treatment with 5-fluoro-2-oxindole alone and/or combined with morphine are two remarkable new procedures for chronic inflammatory pain management. Full article
(This article belongs to the Special Issue Antioxidants in Chronic Pain)
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20 pages, 1984 KiB  
Article
The Circadian Hormone Melatonin Inhibits Morphine-Induced Tolerance and Inflammation via the Activation of Antioxidative Enzymes
by Ing-Jung Chen, Chih-Ping Yang, Sheng-Hsiung Lin, Chang-Mei Lai and Chih-Shung Wong
Antioxidants 2020, 9(9), 780; https://doi.org/10.3390/antiox9090780 - 22 Aug 2020
Cited by 10 | Viewed by 4359
Abstract
Opioids are commonly prescribed for clinical pain management; however, dose-escalation, tolerance, dependence, and addiction limit their usability for long-term chronic pain. The associated poor sleep pattern alters the circadian neurobiology, and further compromises the pain management. Here, we aim to determine the correlation [...] Read more.
Opioids are commonly prescribed for clinical pain management; however, dose-escalation, tolerance, dependence, and addiction limit their usability for long-term chronic pain. The associated poor sleep pattern alters the circadian neurobiology, and further compromises the pain management. Here, we aim to determine the correlation between constant light exposure and morphine tolerance and explore the potential of melatonin as an adjuvant of morphine for neuropathic pain treatment. Methods: Wistar rats were preconditioned under constant light (LL) or a regular light/dark (LD) cycle before neuropathic pain induction by chronic constriction injury. An intrathecal (i.t.) osmotic pump was used for continued drug delivery to induce morphine tolerance. Pain assessments, including the plantar test, static weight-bearing symmetry, and tail-flick latency, were used to determine the impact of the light disruption or exogenous melatonin on the morphine tolerance progression. Results: constant light exposure significantly aggravates morphine tolerance in neuropathic rats. Continued infusion of low-dose melatonin (3 μg/h) attenuated morphine tolerance in both neuropathic and naïve rats. This protective effect was independent of melatonin receptors, as shown by the neutral effect of melatonin receptors inhibitors. The transcriptional profiling demonstrated a significant enhancement of proinflammatory and pain-related receptor genes in morphine-tolerant rats. In contrast, this transcriptional pattern was abolished by melatonin coinfusion along with the upregulation of the Kcnip3 gene. Moreover, melatonin increased the antioxidative enzymes SOD2, HO-1, and GPx1 in the spinal cord of morphine-tolerant rats. Conclusion: Dysregulated circadian light exposure significantly compromises the efficacy of morphine’s antinociceptive effect, while the cotreatment with melatonin attenuates morphine tolerance/hyperalgesia development. Our results suggest the potential of melatonin as an adjuvant of morphine in clinical pain management, particularly in patients who need long-term opioid treatment. Full article
(This article belongs to the Special Issue Antioxidants in Chronic Pain)
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12 pages, 1595 KiB  
Article
The Role of Cashew (Anacardium occidentale L.) Nuts on an Experimental Model of Painful Degenerative Joint Disease
by Roberta Fusco, Rosalba Siracusa, Alesso Filippo Peritore, Enrico Gugliandolo, Tiziana Genovese, Ramona D’Amico, Marika Cordaro, Rosalia Crupi, Giuseppina Mandalari, Daniela Impellizzeri, Salvatore Cuzzocrea and Rosanna Di Paola
Antioxidants 2020, 9(6), 511; https://doi.org/10.3390/antiox9060511 - 10 Jun 2020
Cited by 61 | Viewed by 5820
Abstract
Osteoarthritis is a progressive joint disease characterized by the activation of different molecular mediators, including proinflammatory cytokines, reactive oxygen species, metalloproteinases and nociceptive mediators. Anacardium occidentale L. is a medicinal plant with anti-oxidative and anti-inflammatory properties. In this study we evaluate the effects [...] Read more.
Osteoarthritis is a progressive joint disease characterized by the activation of different molecular mediators, including proinflammatory cytokines, reactive oxygen species, metalloproteinases and nociceptive mediators. Anacardium occidentale L. is a medicinal plant with anti-oxidative and anti-inflammatory properties. In this study we evaluate the effects of cashew nuts (from Anacardium occidentale L.) oral administration on an experimental model of painful degenerative joint disease. Monosodium iodoacetate (MIA) was intraarticularly injected, and cashew nuts were orally administered three times per week for 21 days, starting the third day after MIA injection. Nociception was evaluated by a Von Frey filament test, and motor function by walking track analysis at 3, 7, 14 and 21 days after osteoarthritis. Histological and biochemical alteration were examined at the end of the experiment. Cashew nuts administration reduced pain-like behavior and showed antioxidant activities, restoring biochemical serum parameters: glutathione (GSH), catalase (CAT) levels, glutathione peroxidase (GPx) activity and lipid peroxidation. Moreover, cashew nuts ameliorated radiographic and histological alteration, resulting in decreased cartilage degradation, pro-inflammatory cytokines and metalloproteinases levels and mast cells recruitment. Our results demonstrated that the oral assumption of cashew nuts counteracts the inflammatory and oxidative process involved in osteoarthritis. Full article
(This article belongs to the Special Issue Antioxidants in Chronic Pain)
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