The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/10/1859 |
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| author | Irene Suárez-Rojas Montse Pérez-Fernández Xue Bai Ignacio Martínez-Martel Sebastiano Intagliata Valeria Pittalà Loredana Salerno Olga Pol |
| author_facet | Irene Suárez-Rojas Montse Pérez-Fernández Xue Bai Ignacio Martínez-Martel Sebastiano Intagliata Valeria Pittalà Loredana Salerno Olga Pol |
| author_sort | Irene Suárez-Rojas |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T21:29:46Z |
| format | Article |
| id | doaj.art-cdabdd8d52d54e6885020d46168e7069 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T21:29:46Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-cdabdd8d52d54e6885020d46168e70692023-11-19T15:28:10ZengMDPI AGAntioxidants2076-39212023-10-011210185910.3390/antiox12101859The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms ImplicatedIrene Suárez-Rojas0Montse Pérez-Fernández1Xue Bai2Ignacio Martínez-Martel3Sebastiano Intagliata4Valeria Pittalà5Loredana Salerno6Olga Pol7Grup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainGrup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainGrup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainGrup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainDepartment of Drug and Health Sciences, University of Catania, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, 95125 Catania, ItalyGrup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau), 08041 Barcelona, SpainNeuropathic 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.https://www.mdpi.com/2076-3921/12/10/1859analgesiaanxietydepressiondimethyl fumarateheme oxygenase 1inflammasome |
| spellingShingle | Irene Suárez-Rojas Montse Pérez-Fernández Xue Bai Ignacio Martínez-Martel Sebastiano Intagliata Valeria Pittalà Loredana Salerno Olga Pol The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated Antioxidants analgesia anxiety depression dimethyl fumarate heme oxygenase 1 inflammasome |
| title | The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated |
| title_full | The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated |
| title_fullStr | The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated |
| title_full_unstemmed | The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated |
| title_short | The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated |
| title_sort | inhibition of neuropathic pain incited by nerve injury and accompanying mood disorders by new heme oxygenase 1 inducers mechanisms implicated |
| topic | analgesia anxiety depression dimethyl fumarate heme oxygenase 1 inflammasome |
| url | https://www.mdpi.com/2076-3921/12/10/1859 |
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