Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.8
7.0
Journals
Antioxidants
Special Issues
Antioxidants in Chronic Pain II
share announcement

Antioxidants in Chronic Pain II

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 (15 March 2022) | Viewed by 22166

Special Issue Editor

Dr. Olga Pol

E-Mail Website
Guest Editor
Grup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica 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; nitric oxide; Nrf2 transcription factor; oxidative stress; pain; opioids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Chronic pain, defined as a syndrome characterized by persistent suffering for long periods of time, can be originated and manifested in different forms, including diabetic neuropathy, osteoarthritic pain, inflammatory pain, or neuropathic pain, and affects a high percentage of people. When pain is prolonged for long periods of time it is also accompanied by emotional disorders such as depression, anxiety, and cognitive deficits, which exert a negative impact on the perception of pain and lead to a significant deterioration in the patient’s quality of life. The optimum treatment of chronic pain is an unmet medical need and a major challenge in pain research, considering that current therapies have limited effectiveness and important side effects. 

Oxidative stress is highly implicated in the development of chronic pain and the associated emotional disorders. Reactive oxygen species (ROS) are elevated in the central and peripheral nervous system of animals with chronic pain, and ROS scavengers alleviate hyperalgesia. The role of several antioxidants in pain relief by attenuating ROS generation and/or by activating the endogenous antioxidant system triggered by the nuclear factor erythroid-2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1), NADPH quinone oxidoreductase 1, superoxide dismutase, glutathione peroxidase 1, and/or the catalase signaling pathway has been demonstrated. Thus, Nrf2/HO-1 activators modulate the pronociceptive responses generated by nerve damage, inflammation, chemotherapeutic agents and/or hyperglycemia, being a good therapeutic strategy. 

There is a wide variety of antioxidant compounds with different structures and chemical properties whose analgesic properties and mechanisms of action during chronic pain have not been identified. This Special Issue on “Antioxidants in Chronic Pain II” 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 to advance 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 (8 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, Other

14 pages, 2318 KiB  
Article
The Interaction between Carbon Monoxide and Hydrogen Sulfide during Chronic Joint Pain in Young Female Mice
by Gerard Batallé, Xue Bai and Olga Pol
Antioxidants 2022, 11(7), 1271; https://doi.org/10.3390/antiox11071271 - 27 Jun 2022
Cited by 8 | Viewed by 1576
Abstract
A relationship between carbon monoxide (CO) and hydrogen sulfide (H2S) has been described in different pathological conditions, but their interaction in modulating joint pain has not yet been investigated. In young female mice with monosodium acetate-induced joint degeneration and pain, we [...] Read more.
A relationship between carbon monoxide (CO) and hydrogen sulfide (H2S) has been described in different pathological conditions, but their interaction in modulating joint pain has not yet been investigated. In young female mice with monosodium acetate-induced joint degeneration and pain, we assessed: (1) the effects of CORM-2 (tricarbonyldichlororuthenium(II)dimer), a CO-releasing molecule, and CoPP (cobalt protoporphyrin IX), an inducer of heme oxygenase 1 (HO-1), administered alone and combined with low doses of two slow-releasing H2S donors, DADS (diallyl disulfide) and GYY4137 (morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex) on the mechanical allodynia and loss of grip strength provoked by joint degeneration; (2) the role of Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1) and HO-1 in the antinociceptive actions of H2S donors; (3) the impact of DADS and GYY4137 treatment on the expression of Nrf2 and several antioxidant proteins in dorsal root ganglia (DRG) and periaqueductal gray matter (PAG). Our data showed that treatment with H2S donors inhibited allodynia and functional deficits, while CORM-2 and CoPP only prevented allodynia. The Nrf2 pathway is implicated in the analgesic actions of DADS and GYY4137 during joint degeneration. Moreover, the co-administration of low doses of CORM-2 or CoPP with DADS or GYY4137 produced higher antiallodynic effects and greater recovery of grip strength deficits than those produced by each of these compounds alone. The activation of the antioxidant system caused by H2S donors in DRG and/or PAG might explain the enhancement of antinociceptive effects. These data reveal a positive interaction between H2S and CO in modulating joint pain in female mice. Full article
(This article belongs to the Special Issue Antioxidants in Chronic Pain II)
►▼ Show Figures

Figure 1

20 pages, 4368 KiB  
Article
The Antinociceptive Potential of Camellia japonica Leaf Extract, (−)-Epicatechin, and Rutin against Chronic Constriction Injury-Induced Neuropathic Pain in Rats
by Eun Yeong Lim, Changho Lee and Yun Tai Kim
Antioxidants 2022, 11(2), 410; https://doi.org/10.3390/antiox11020410 - 17 Feb 2022
Cited by 6 | Viewed by 2473
Abstract
Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. Camellia japonica leaves are known to have antioxidant and anti-inflammatory properties.; however, their antinociceptive efficacy has not yet been [...] Read more.
Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. Camellia japonica leaves are known to have antioxidant and anti-inflammatory properties.; however, their antinociceptive efficacy has not yet been explored. We examined the antinociceptive efficacy and underlying mechanism of C. japonica leaf extract (CJE) in chronic constriction injury (CCI)-induced neuropathic pain models. To test the antinociceptive activity of CJE, three types of allodynia were evaluated: punctate allodynia using von Frey filaments, dynamic allodynia using a paintbrush and cotton swab, and cold allodynia using a cold plate test. CCI rats developed neuropathic pain representing increases in the three types of allodynia and spontaneous pain. In addition, CCI rats showed high phosphorylation levels of mitogen-activated protein kinases (MAPKs), transcription factors, and nociceptive mediators in dorsal root ganglion (DRG). The ionized calcium-binding adapter molecule 1 levels and neuroinflammation also increased following CCI surgery in the spinal cord. CJE and its active components have potential antinociceptive effects against CCI-induced neuropathic pain that might be mediated by MAPK activation in the DRG and microglial activation in the spinal cord. These findings suggest that CJE, (−)-epicatechin, and rutin could be novel candidates for neuropathic pain management. Full article
(This article belongs to the Special Issue Antioxidants in Chronic Pain II)
►▼ Show Figures

Graphical abstract

19 pages, 2904 KiB  
Article
The Beneficial Effects of Heme Oxygenase 1 and Hydrogen Sulfide Activation in the Management of Neuropathic Pain, Anxiety- and Depressive-like Effects of Paclitaxel in Mice
by Gerard Roch, Gerard Batallé, Xue Bai, Enric Pouso-Vázquez, Laura Rodríguez and Olga Pol
Antioxidants 2022, 11(1), 122; https://doi.org/10.3390/antiox11010122 - 06 Jan 2022
Cited by 8 | Viewed by 2195
Abstract
Chemotherapy-induced peripheral neuropathy constitutes an unresolved clinical problem that severely decreases the quality of the patient’s life. It is characterized by somatosensory alterations, including chronic pain, and a high risk of suffering mental disorders such as depression and anxiety. Unfortunately, an effective treatment [...] Read more.
Chemotherapy-induced peripheral neuropathy constitutes an unresolved clinical problem that severely decreases the quality of the patient’s life. It is characterized by somatosensory alterations, including chronic pain, and a high risk of suffering mental disorders such as depression and anxiety. Unfortunately, an effective treatment for this neuropathology is yet to be found. We investigated the therapeutic potential of cobalt protoporphyrin IX (CoPP), a heme oxygenase 1 inducer, and morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137), a slow hydrogen sulfide (H2S) donor, in a preclinical model of paclitaxel (PTX)-induced peripheral neuropathy (PIPN) in mice. At three weeks after PTX injection, we evaluated the effects of the repetitive administration of 5 mg/kg of CoPP and 35 mg/kg of GYY4137 on PTX-induced nociceptive symptoms (mechanical and cold allodynia) and on the associated emotional disturbances (anxiety- and depressive-like behaviors). We also studied the mechanisms that could mediate their therapeutic properties by evaluating the expression of key proteins implicated in the development of nociception, oxidative stress, microglial activation, and apoptosis in prefrontal cortex (PFC) and dorsal root ganglia (DRG) of mice with PIPN. Results demonstrate that CoPP and GYY4137 treatments inhibited both the nociceptive symptomatology and the derived emotional alterations. These actions were mainly mediated through potentiation of antioxidant responses and inhibiting oxidative stress in the DRG and/or PFC of mice with PIPN. Both treatments normalized some plasticity changes and apoptotic reactions, and GYY4137 blocked microglial activation induced by PTX in PFC. In conclusion, this study proposes CoPP and GYY4137 as good candidates for treating neuropathic pain, anxiety- and depressive-like effects of PTX. Full article
(This article belongs to the Special Issue Antioxidants in Chronic Pain II)
►▼ Show Figures

Figure 1

17 pages, 3597 KiB  
Article
The Recovery of Cognitive and Affective Deficiencies Linked with Chronic Osteoarthritis Pain and Implicated Pathways by Slow-Releasing Hydrogen Sulfide Treatment
by Gerard Batallé, Xue Bai, Enric Pouso-Vázquez, Gerard Roch, Laura Rodríguez and Olga Pol
Antioxidants 2021, 10(10), 1632; https://doi.org/10.3390/antiox10101632 - 16 Oct 2021
Cited by 13 | Viewed by 2556
Abstract
Chronic osteoarthritis pain is accompanied by several comorbidities whose treatment has not been completely resolved. The anti-inflammatory, analgesic, and antidepressant effects of slow-releasing hydrogen sulfide (H2S) donors during osteoarthritic pain have been shown, but their actions in the accompanying memory impairment [...] Read more.
Chronic osteoarthritis pain is accompanied by several comorbidities whose treatment has not been completely resolved. The anti-inflammatory, analgesic, and antidepressant effects of slow-releasing hydrogen sulfide (H2S) donors during osteoarthritic pain have been shown, but their actions in the accompanying memory impairment and anxious-like behaviors have not yet been demonstrated. Using female mice with chronic osteoarthritic pain, the effects of natural, diallyl disulfide (DADS) or synthetic, morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137) slow-releasing H2S donors, on associated cognitive and grip strength deficits and anxiodepressive-like behaviors, were assessed. Their effects on specific brain areas implicated in the modulation of pain and emotional responses were also determined. Results demonstrated an improvement in memory and grip strength deficits, as well as in the anxious-like behaviors associated with chronic pain in GYY4137 and/or DADS treated mice. The painkiller and antidepressant properties of both treatments were also established. Treatment with DADS and/or GYY4137 inhibited: oxidative stress in the amygdala; phosphoinositide 3-kinase overexpression in the amygdala, periaqueductal gray matter, and anterior cingulate cortex; protein kinase B activation in the amygdala and infralimbic cortex; up-regulation of inducible nitric oxide synthase in the amygdala, periaqueductal gray matter and infralimbic cortex and apoptotic responses in the amygdala. These results might explain the recovery of memory and grip strength and the inhibition of allodynia and associated anxiodepressive-like behaviors by these treatments. In conclusion, this study revealed new properties of slow-releasing H2S donors in cognitive impairment and affective disorders linked with chronic osteoarthritis pain and their effects on the central nervous system. Full article
(This article belongs to the Special Issue Antioxidants in Chronic Pain II)
►▼ Show Figures

Figure 1

18 pages, 4450 KiB  
Article
The Anxiolytic and Antidepressant Effects of Diallyl Disulfide and GYY4137 in Animals with Chronic Neuropathic Pain
by Xue Bai, Gerard Batallé and Olga Pol
Antioxidants 2021, 10(7), 1074; https://doi.org/10.3390/antiox10071074 - 03 Jul 2021
Cited by 14 | Viewed by 2848
Abstract
When neuropathic pain is maintained long term, it can also lead to the development of emotional disorders that are even more intense than pain perception and difficult to treat. Hydrogen sulfide (H2S) donors relieve chronic pain, but their effects on the [...] Read more.
When neuropathic pain is maintained long term, it can also lead to the development of emotional disorders that are even more intense than pain perception and difficult to treat. Hydrogen sulfide (H2S) donors relieve chronic pain, but their effects on the associated mood disorders are not completely elucidated. We evaluated if treatment with DADS (diallyl disulfide) or GYY4137 (morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex), two slow-releasing H2S donors, inhibits the anxiety- and depressive-like behaviors that concur with chronic neuropathic pain generated by sciatic nerve injury in mice. The modulatory role of these drugs in the inflammatory, apoptotic, and oxidative processes implicated in the development of the affective disorders was assessed. Our results revealed the anxiolytic, antidepressant, and antinociceptive properties of DADS and GYY4137 during neuropathic pain by inhibiting microglial activation and the up-regulation of phosphoinositide 3-kinase/phosphorylated protein kinase B and BAX in the amygdala (AMG) and/or periaqueductal gray matter (PAG). Both treatments also normalized and/or activated the endogenous antioxidant system, but only DADS blocked ERK 1/2 phosphorylation. Both H2S donors decreased allodynia and hyperalgesia in a dose-dependent manner by activating the Kv7 potassium channels and heme oxygenase 1 signaling pathways. This study provides evidence of the anxiolytic and antidepressant properties of DADS and GYY4137 during neuropathic pain and reveals their analgesic actions, suggesting that these therapeutic properties may result from the inhibition of the inflammatory, apoptotic, and oxidative responses in the AMG and/or PAG. These findings support the use of these treatments for the management of affective disorders accompanying chronic neuropathic pain. Full article
(This article belongs to the Special Issue Antioxidants in Chronic Pain II)
►▼ Show Figures

Figure 1

Review

Jump to: Research, Other

17 pages, 1411 KiB  
Review
NADPH Oxidases in Pain Processing
by Wiebke Kallenborn-Gerhardt, Katrin Schröder and Achim Schmidtko
Antioxidants 2022, 11(6), 1162; https://doi.org/10.3390/antiox11061162 - 14 Jun 2022
Cited by 4 | Viewed by 2501
Abstract
Inflammation or injury to the somatosensory nervous system may result in chronic pain conditions, which affect millions of people and often cause major health problems. Emerging lines of evidence indicate that reactive oxygen species (ROS), such as superoxide anion or hydrogen peroxide, are [...] Read more.
Inflammation or injury to the somatosensory nervous system may result in chronic pain conditions, which affect millions of people and often cause major health problems. Emerging lines of evidence indicate that reactive oxygen species (ROS), such as superoxide anion or hydrogen peroxide, are produced in the nociceptive system during chronic inflammatory and neuropathic pain and act as specific signaling molecules in pain processing. Among potential ROS sources in the somatosensory system are NADPH oxidases, a group of electron-transporting transmembrane enzymes whose sole function seems to be the generation of ROS. Interestingly, the expression and relevant function of the Nox family members Nox1, Nox2, and Nox4 in various cells of the nociceptive system have been demonstrated. Studies using knockout mice or specific knockdown of these isoforms indicate that Nox1, Nox2, and Nox4 specifically contribute to distinct signaling pathways in chronic inflammatory and/or neuropathic pain states. As selective Nox inhibitors are currently being developed and investigated in various physiological and pathophysiological settings, targeting Nox1, Nox2, and/or Nox4 could be a novel strategy for the treatment of chronic pain. Here, we summarize the distinct roles of Nox1, Nox2, and Nox4 in inflammatory and neuropathic processing and discuss the effectiveness of currently available Nox inhibitors in the treatment of chronic pain conditions. Full article
(This article belongs to the Special Issue Antioxidants in Chronic Pain II)
►▼ Show Figures

Figure 1

23 pages, 22379 KiB  
Review
The Effects of Nuclear Factor Erythroid 2 (NFE2)-Related Factor 2 (Nrf2) Activation in Preclinical Models of Peripheral Neuropathic Pain
by Paramita Basu, Dayna L. Averitt, Camelia Maier and Arpita Basu
Antioxidants 2022, 11(2), 430; https://doi.org/10.3390/antiox11020430 - 21 Feb 2022
Cited by 21 | Viewed by 4737
Abstract
Oxidative stress, resulting from an imbalance between the formation of damaging free radicals and availability of protective antioxidants, can contribute to peripheral neuropathic pain conditions. Reactive oxygen and nitrogen species, as well as products of the mitochondrial metabolism such as superoxide anions, hydrogen [...] Read more.
Oxidative stress, resulting from an imbalance between the formation of damaging free radicals and availability of protective antioxidants, can contribute to peripheral neuropathic pain conditions. Reactive oxygen and nitrogen species, as well as products of the mitochondrial metabolism such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, are common free radicals. Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) is a transcription factor encoded by the NFE2L2 gene and is a member of the cap ‘n’ collar subfamily of basic region leucine zipper transcription factors. Under normal physiological conditions, Nrf2 remains bound to Kelch-like ECH-associated protein 1 in the cytoplasm that ultimately leads to proteasomal degradation. During peripheral neuropathy, Nrf2 can translocate to the nucleus, where it heterodimerizes with muscle aponeurosis fibromatosis proteins and binds to antioxidant response elements (AREs). It is becoming increasingly clear that the Nrf2 interaction with ARE leads to the transcription of several antioxidative enzymes that can ameliorate neuropathy and neuropathic pain in rodent models. Current evidence indicates that the antinociceptive effects of Nrf2 occur via reducing oxidative stress, neuroinflammation, and mitochondrial dysfunction. Here, we will summarize the preclinical evidence supporting the role of Nrf2 signaling pathways and Nrf2 inducers in alleviating peripheral neuropathic pain. Full article
(This article belongs to the Special Issue Antioxidants in Chronic Pain II)
►▼ Show Figures

Figure 1

Other

Jump to: Research, Review

22 pages, 2185 KiB  
Systematic Review
A Systematic Review and Meta-Analysis on the Role of Nutraceuticals in the Management of Neuropathic Pain in In Vivo Studies
by Sara Ilari, Stefania Proietti, Patrizia Russo, Valentina Malafoglia, Micaela Gliozzi, Jessica Maiuolo, Francesca Oppedisano, Ernesto Palma, Carlo Tomino, Massimo Fini, William Raffaeli, Vincenzo Mollace, Stefano Bonassi and Carolina Muscoli
Antioxidants 2022, 11(12), 2361; https://doi.org/10.3390/antiox11122361 - 28 Nov 2022
Cited by 7 | Viewed by 2100
Abstract
The control of neuropathic pain is a leading challenge in modern medicine. Traditional medicine has, for a long time, used natural compounds such as nutraceuticals for this purpose, and extensive evidence has supported their role in controlling oxidative stress and persistent pain-related inflammation. [...] Read more.
The control of neuropathic pain is a leading challenge in modern medicine. Traditional medicine has, for a long time, used natural compounds such as nutraceuticals for this purpose, and extensive evidence has supported their role in controlling oxidative stress and persistent pain-related inflammation. Nutraceuticals are natural products belonging to the food sector whose consumption could be related to physiological benefits. Indeed, they are used to improve health, prevent chronic diseases, and delay the aging process. Here, we report a systematic review and meta-analysis to provide a more comprehensive report on the use of nutraceuticals in neuropathic pain, including evaluating confounding factors. A search of the literature has been conducted on principal databases (PubMed, MEDLINE, EMBASE, and Web of Science) following the PRISMA statement, and we retrieved 484 articles, 12 of which were selected for the meta-analysis. The results showed that administration of natural drugs in animals with neuropathic pain led to a significant reduction in thermal hyperalgesia, measured in both the injured paw (SMD: 1.79; 95% CI: 1.41 to 2.17; p < 0.0001) and in the two paws (SMD: −1.74; 95% CI: −3.36 to −0.11; p = 0.036), as well as a reduction in mechanical allodynia and hyperalgesia (SMD: 1.95, 95% CI: 1.08 to 2.82; p < 0.001) when compared to controls. The results of the review indicate that nutraceutical compounds could be clinically relevant for managing persistent neuropathic pain. Full article
(This article belongs to the Special Issue Antioxidants in Chronic Pain II)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-8
Back to TopTop