Effects of treatment with a carbon monoxide donor and an activator of heme oxygenase 1 on the nociceptive, apoptotic and/or oxidative alterations induced by persistent inflammatory pain in the central nervous system of mice

Cazuza, Rafael Alves; Batallé, Gerard; Bai, Xue; Leite-Panissi, Christie R.A.; Pol, Olga

doi:10.1016/j.brainresbull.2022.08.004

Cited by 6 publications

(6 citation statements)

References 51 publications

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“…The analgesic effects produced by 1m, 1a, and 1b, as well as DMF, agreed with previous research revealing the painkiller properties of DMF in animals with arthritis [19]; those produced by another HO-1 inducer, cobalt protoporphyrin IX (CoPP), in mice with CFAinduced inflammatory pain [38,39]; and that made by lentivirus encoding HO-1 in animals with vincristine provoked neuropathic pain [40]. The recovery of functional disabilities produced by 1m, 1a, 1b, and DMF during inflammatory pain agreed with the improvement of the grip strength deficits induced by DMF in animals with the sciatic nerve crushed [23] or with multiple sclerosis [24].…”

Section: Discussionsupporting

confidence: 89%

Novel Heme Oxygenase-1 Inducers Palliate Inflammatory Pain and Emotional Disorders by Regulating NLRP3 Inflammasome and Activating the Antioxidant Pathway

Pérez-Fernández,

Suárez-Rojas,

Bai

et al. 2023

Antioxidants

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Chronic pain caused by persistent inflammation is current in multiple diseases and has a strong negative impact on society. It is commonly associated with several mental illnesses, which can exert a negative influence on pain perception, and needs to be eradicated. Nevertheless, actual therapies are not sufficiently safe and effective. Recent reports demonstrate that the induction of heme oxygenase-1 (HO-1) enzyme produces analgesic effects in animals with osteoarthritis pain and reverses the grip strength loss caused by sciatic nerve crush. In this research, we evaluated the potential use of three new HO-1 inducers, 1m, 1a, and 1b, as well as dimethyl fumarate (DMF), for treating persistent inflammatory pain induced by the subplantar injection of complete Freud’s adjuvant and the functional deficits and emotional sickness associated. The modulator role of these treatments on the inflammatory and antioxidant pathways were also assessed. Our findings revealed that repeated treatment, for four days, with 1m, 1a, 1b, or DMF inhibited inflammatory pain, reversed grip strength deficits, and reversed the linked anxious- and depressive-like behaviors, with 1m being the most effective. These treatments also suppressed the up-regulation of the inflammasome NLRP3 and activated the expression of the Nrf2 transcription factor and the HO-1 and superoxide dismutase 1 enzymes in the paw and/or amygdala, thus revealing the anti-inflammatory and antioxidant capacity of these compounds during inflammatory pain. Results suggest the use of 1m, 1a, 1b, and DMF, particularly 1m, as promising therapies for inflammatory pain and the accompanying functional disabilities and emotional diseases.

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Section: Discussionsupporting

confidence: 89%

Novel Heme Oxygenase-1 Inducers Palliate Inflammatory Pain and Emotional Disorders by Regulating NLRP3 Inflammasome and Activating the Antioxidant Pathway

Pérez-Fernández,

Suárez-Rojas,

Bai

et al. 2023

Antioxidants

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“…The neuroprotective effects of DMF in neurodegenerative disorders [7], as well as in osteoarthritis pain, post-operative pain, and neuropathic pain caused by spare nerve injury or by chemotherapeutic agents, have been demonstrated [22,23,39,40]. Other studies also revealed that another Nrf2 activator, sulforaphane, as well as the HO-1 inducer, CoPP, both inhibited neuropathic pain provoked by CCI or associated with diabetes [24,25,41,42] and inflammatory pain caused by CFA injection [27]. These studies showed that between three and fourteen days of treatment are required for the complete inhibition of the me-chanical allodynia related to neuropathic or inflammatory pain.…”

Section: Discussionmentioning

confidence: 95%

“…These genes include, besides HO-1, glutathione S-transferase Mu 1 (GSTM1), superoxide dismutase 1 (SOD-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) [21]. In consequence, it has been shown that several Nrf2 activators, such as dimethyl fumarate (DMF) [22,23], and HO-1 inducers, for instance, cobalt protoporphyrin IX (CoPP), inhibit neuropathic pain provoked by chemotherapy or sciatic nerve injury [24][25][26], as well as the inflammatory pain provoked by the subplantar administration of complete Freund's adjuvant (CFA) [27]. In addition, Casili et al (2020) [28] demonstrated that DMF reduced the rates of anxiety and depression associated with migraine in mice, but these effects during neuropathic pain have not yet been evaluated.…”

Section: Introductionmentioning

confidence: 99%

The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated

Suárez-Rojas,

Pérez-Fernández,

Bai

et al. 2023

Antioxidants

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Neuropathic pain is a type of pain that persists for a long time and becomes pathological. Additionally, the anxiodepressive disorders derived from neuropathic pain are difficult to palliate with the current treatments and need to be resolved. Then, using male mice with neuropathic pain provoked by chronic constriction of the sciatic nerve (CCI), we analyzed and compared the analgesic actions produced by three new heme oxygenase 1 (HO-1) inducers, 1m, 1b, and 1a, with those performed by dimethyl fumarate (DMF). Their impact on the anxiety- and depressive-like comportments and the expression of the inflammasome NLRP3, Nrf2, and some antioxidant enzymes in the dorsal root ganglia (DRG) and amygdala (AMG) were also investigated. Results revealed that the administration of 1m, 1b, and DMF given orally for four days inhibited the allodynia and hyperalgesia caused by CCI, while 1a merely reduced the mechanical allodynia. However, in the first two days of treatment, the antiallodynic effects produced by 1m were higher than those of 1a and DMF, and its antihyperalgesic actions were greater than those produced by 1b, 1a, and DMF, revealing that 1m was the most effective compound. At four days of treatment, all drugs exerted anxiolytic and antidepressant effects, decreased the NLRP3 levels, and increased/normalized the Nrf2, HO-1, and superoxide dismutase 1 levels in DRG and AMG. Data indicated that the dual modulation of the antioxidant and inflammatory pathways produced by these compounds, especially 1m, is a new promising therapeutic approach for neuropathic pain and related emotional illnesses.

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“…This study further proved the anti-apoptotic activities induced by the systemic administration of HRW in the amygdala of animals with persistent chronic inflammatory pain as occurs in the paw, revealing the anti-apoptotic properties of H 2 during chronic inflammatory pain as displayed in other health disorders [ 47 ]. Similarly, the protective role played by other gases, such as carbon monoxide, in modulating the apoptotic reactions caused by peripheral inflammation in the CNS has also been shown [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in Mice

et al. 2022

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Chronic inflammatory pain is manifested in many diseases. The potential use of molecular hydrogen (H2) as a new therapy for neurological disorders has been demonstrated. Recent studies prove its analgesic properties in animals with neuropathic pain, but the possible antinociceptive, antidepressant, and/or anxiolytic actions of H2 during persistent inflammatory pain have not been investigated. Therefore, using male mice with chronic inflammatory pain incited by the subplantar injection of complete Freud’s adjuvant (CFA), we assessed the actions of hydrogen-rich water (HRW) systemically administered on: (1) the nociceptive responses and affective disorders associated and (2) the oxidative (4-hydroxy-2-nonenal; 4-HNE), inflammatory (phosphorylated-NF-kB inhibitor alpha; p-IKBα), and apoptotic (Bcl-2-like protein 4; BAX) changes provoked by CFA in the paws and amygdala. The role of the antioxidant system in the analgesia induced by HRW systemically and locally administered was also determined. Our results revealed that the intraperitoneal administration of HRW, besides reducing inflammatory pain, also inhibited the depressive- and anxiolytic-like behaviors associated and the over expression of 4-HNE, p-IKBα, and BAX in paws and amygdala. The contribution of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 and NAD(P)H: quinone oxidoreductase 1 pathway in the analgesic activities of HRW, systemically or locally administered, was also shown. These data revealed the analgesic, antidepressant, and anxiolytic actions of HRW. The protective, anti-inflammatory, and antioxidant qualities of this treatment during inflammatory pain were also demonstrated. Therefore, this study proposes the usage of HRW as a potential therapy for chronic inflammatory pain and linked comorbidities.

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Effects of treatment with a carbon monoxide donor and an activator of heme oxygenase 1 on the nociceptive, apoptotic and/or oxidative alterations induced by persistent inflammatory pain in the central nervous system of mice

Cited by 6 publications

References 51 publications

Novel Heme Oxygenase-1 Inducers Palliate Inflammatory Pain and Emotional Disorders by Regulating NLRP3 Inflammasome and Activating the Antioxidant Pathway

Novel Heme Oxygenase-1 Inducers Palliate Inflammatory Pain and Emotional Disorders by Regulating NLRP3 Inflammasome and Activating the Antioxidant Pathway

The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated

Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in Mice

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