Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System
Oxidative stress resulting from reactive oxygen species (ROS) is known to play a key role in numerous neurological disorders, including neuropathic pain. Morphine is one of the commonly used opioids for pain management. However, long-term administration of morphine results in morphine antinociceptiv...
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MDPI AG
2021-01-01
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| Series: | Antioxidants |
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| author | Yaswanth Kuthati Prabhakar Busa Srikrishna Tummala Vaikar Navakanth Rao Venkata Naga Goutham Davuluri Yen-Peng Ho Chih-Shung Wong |
| author_facet | Yaswanth Kuthati Prabhakar Busa Srikrishna Tummala Vaikar Navakanth Rao Venkata Naga Goutham Davuluri Yen-Peng Ho Chih-Shung Wong |
| author_sort | Yaswanth Kuthati |
| collection | DOAJ |
| description | Oxidative stress resulting from reactive oxygen species (ROS) is known to play a key role in numerous neurological disorders, including neuropathic pain. Morphine is one of the commonly used opioids for pain management. However, long-term administration of morphine results in morphine antinociceptive tolerance (MAT) through elevation of ROS and suppression of natural antioxidant defense mechanisms. Recently, mesoporous polydopamine (MPDA) nanoparticles (NPS) have been known to possess strong antioxidant properties. We speculated that morphine delivery through an antioxidant nanocarrier might be a reasonable strategy to alleviate MAT. MPDAs showed a high drug loading efficiency of ∼50%, which was much higher than conventional NPS. Spectral and in vitro studies suggest a superior ROS scavenging ability of NPS. Results from a rat neuropathic pain model demonstrate that MPDA-loaded morphine (MPDA@Mor) is efficient in minimizing MAT with prolonged analgesic effect and suppression of pro-inflammatory cytokines. Additionally, serum levels of liver enzymes and levels of endogenous antioxidants were measured in the liver. Treatment with free morphine resulted in elevated levels of liver enzymes and significantly lowered the activities of endogenous antioxidant enzymes in comparison with the control and MPDA@Mor-treated group. Histopathological examination of the liver revealed that MPDA@Mor can significantly reduce the hepatotoxic effects of morphine. Taken together, our current work will provide an important insight into the development of safe and effective nano-antioxidant platforms for neuropathic pain management. |
| first_indexed | 2024-03-09T03:20:54Z |
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| issn | 2076-3921 |
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| last_indexed | 2024-03-09T03:20:54Z |
| publishDate | 2021-01-01 |
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| series | Antioxidants |
| spelling | doaj.art-e3f7e2a4de8e41bd8ded92641c39e5392023-12-03T15:12:10ZengMDPI AGAntioxidants2076-39212021-01-0110219510.3390/antiox10020195Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant SystemYaswanth Kuthati0Prabhakar Busa1Srikrishna Tummala2Vaikar Navakanth Rao3Venkata Naga Goutham Davuluri4Yen-Peng Ho5Chih-Shung Wong6Department of Anesthesiology, Cathy General Hospital, Taipei 280, TaiwanDepartment of Life Sciences, National Dong Hwa University, Hualien 97401, TaiwanDepartment of Chemistry, National Dong Hwa University, Hualien 97401, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, TaiwanDepartment of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, TaiwanDepartment of Chemistry, National Dong Hwa University, Hualien 97401, TaiwanDepartment of Anesthesiology, Cathy General Hospital, Taipei 280, TaiwanOxidative stress resulting from reactive oxygen species (ROS) is known to play a key role in numerous neurological disorders, including neuropathic pain. Morphine is one of the commonly used opioids for pain management. However, long-term administration of morphine results in morphine antinociceptive tolerance (MAT) through elevation of ROS and suppression of natural antioxidant defense mechanisms. Recently, mesoporous polydopamine (MPDA) nanoparticles (NPS) have been known to possess strong antioxidant properties. We speculated that morphine delivery through an antioxidant nanocarrier might be a reasonable strategy to alleviate MAT. MPDAs showed a high drug loading efficiency of ∼50%, which was much higher than conventional NPS. Spectral and in vitro studies suggest a superior ROS scavenging ability of NPS. Results from a rat neuropathic pain model demonstrate that MPDA-loaded morphine (MPDA@Mor) is efficient in minimizing MAT with prolonged analgesic effect and suppression of pro-inflammatory cytokines. Additionally, serum levels of liver enzymes and levels of endogenous antioxidants were measured in the liver. Treatment with free morphine resulted in elevated levels of liver enzymes and significantly lowered the activities of endogenous antioxidant enzymes in comparison with the control and MPDA@Mor-treated group. Histopathological examination of the liver revealed that MPDA@Mor can significantly reduce the hepatotoxic effects of morphine. Taken together, our current work will provide an important insight into the development of safe and effective nano-antioxidant platforms for neuropathic pain management.https://www.mdpi.com/2076-3921/10/2/195morphine antinociceptive toleranceMPDAneuropathic painmorphinereactive oxygen speciesoxidative stress |
| spellingShingle | Yaswanth Kuthati Prabhakar Busa Srikrishna Tummala Vaikar Navakanth Rao Venkata Naga Goutham Davuluri Yen-Peng Ho Chih-Shung Wong Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System Antioxidants morphine antinociceptive tolerance MPDA neuropathic pain morphine reactive oxygen species oxidative stress |
| title | Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System |
| title_full | Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System |
| title_fullStr | Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System |
| title_full_unstemmed | Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System |
| title_short | Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System |
| title_sort | mesoporous polydopamine nanoparticles attenuate morphine tolerance in neuropathic pain rats by inhibition of oxidative stress and restoration of the endogenous antioxidant system |
| topic | morphine antinociceptive tolerance MPDA neuropathic pain morphine reactive oxygen species oxidative stress |
| url | https://www.mdpi.com/2076-3921/10/2/195 |
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