The involvement of the noradrenergic system in the antinociceptive effect of cucurbitacin D on mice with paclitaxel-induced neuropathic pain
Paclitaxel (sold under the brand name Taxol) is a chemotherapeutic drug that is widely used to treat cancer. However, it can also induce peripheral neuropathy, which limits its use. Although several drugs are used to attenuate neuropathy, no optimal treatment is available to date. In this study, the...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1055264/full |
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| author | Keun-Tae Park Suyong Kim Ilseob Choi Ik-Hwan Han Hyunsu Bae Woojin Kim Woojin Kim |
| author_facet | Keun-Tae Park Suyong Kim Ilseob Choi Ik-Hwan Han Hyunsu Bae Woojin Kim Woojin Kim |
| author_sort | Keun-Tae Park |
| collection | DOAJ |
| description | Paclitaxel (sold under the brand name Taxol) is a chemotherapeutic drug that is widely used to treat cancer. However, it can also induce peripheral neuropathy, which limits its use. Although several drugs are used to attenuate neuropathy, no optimal treatment is available to date. In this study, the effect of cucurbitacins B and D on paclitaxel-induced neuropathic pain was assessed. Multiple paclitaxel injections (a cumulative dose of 8 mg/kg, i. p.) induced cold and mechanical allodynia from days 10 to 21 in mice, and the i. p. administration of 0.025 mg/kg of cucurbitacins B and D attenuated both allodynia types. However, as cucurbitacin B showed a more toxic effect on non-cancerous (RAW 264.7) cells, further experiments were conducted with cucurbitacin D. The cucurbitacin D dose-dependently (0.025, 0.1, and 0.5 mg/kg) attenuated both allodynia types. In the spinal cord, paclitaxel injection increased the gene expression of noradrenergic (α1-and α2-adrenergic) receptors but not serotonergic (5-HT1A and 3) receptors. Cucurbitacin D treatment significantly decreased the spinal α1- but not α2-adrenergic receptors, and the amount of spinal noradrenaline was also downregulated. However, the tyrosine hydroxylase expression measured via liquid chromatography in the locus coeruleus did not decrease significantly. Finally, cucurbitacin D treatment did not lower the anticancer effect of chemotherapeutic drugs when co-administered with paclitaxel in CT-26 cell-implanted mice. Altogether, these results suggest that cucurbitacin D could be considered a treatment option against paclitaxel-induced neuropathic pain. |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T00:59:07Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-b6245df8dea54040b8ab31397bd9d4612023-01-04T18:57:06ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-01-011310.3389/fphar.2022.10552641055264The involvement of the noradrenergic system in the antinociceptive effect of cucurbitacin D on mice with paclitaxel-induced neuropathic painKeun-Tae Park0Suyong Kim1Ilseob Choi2Ik-Hwan Han3Hyunsu Bae4Woojin Kim5Woojin Kim6Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaKorean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South KoreaPaclitaxel (sold under the brand name Taxol) is a chemotherapeutic drug that is widely used to treat cancer. However, it can also induce peripheral neuropathy, which limits its use. Although several drugs are used to attenuate neuropathy, no optimal treatment is available to date. In this study, the effect of cucurbitacins B and D on paclitaxel-induced neuropathic pain was assessed. Multiple paclitaxel injections (a cumulative dose of 8 mg/kg, i. p.) induced cold and mechanical allodynia from days 10 to 21 in mice, and the i. p. administration of 0.025 mg/kg of cucurbitacins B and D attenuated both allodynia types. However, as cucurbitacin B showed a more toxic effect on non-cancerous (RAW 264.7) cells, further experiments were conducted with cucurbitacin D. The cucurbitacin D dose-dependently (0.025, 0.1, and 0.5 mg/kg) attenuated both allodynia types. In the spinal cord, paclitaxel injection increased the gene expression of noradrenergic (α1-and α2-adrenergic) receptors but not serotonergic (5-HT1A and 3) receptors. Cucurbitacin D treatment significantly decreased the spinal α1- but not α2-adrenergic receptors, and the amount of spinal noradrenaline was also downregulated. However, the tyrosine hydroxylase expression measured via liquid chromatography in the locus coeruleus did not decrease significantly. Finally, cucurbitacin D treatment did not lower the anticancer effect of chemotherapeutic drugs when co-administered with paclitaxel in CT-26 cell-implanted mice. Altogether, these results suggest that cucurbitacin D could be considered a treatment option against paclitaxel-induced neuropathic pain.https://www.frontiersin.org/articles/10.3389/fphar.2022.1055264/fullallodyniachemotherapy-induced neuropathic paincucurbitacin Bcucurbitacin Dnoradrenergic systempaclitaxel |
| spellingShingle | Keun-Tae Park Suyong Kim Ilseob Choi Ik-Hwan Han Hyunsu Bae Woojin Kim Woojin Kim The involvement of the noradrenergic system in the antinociceptive effect of cucurbitacin D on mice with paclitaxel-induced neuropathic pain Frontiers in Pharmacology allodynia chemotherapy-induced neuropathic pain cucurbitacin B cucurbitacin D noradrenergic system paclitaxel |
| title | The involvement of the noradrenergic system in the antinociceptive effect of cucurbitacin D on mice with paclitaxel-induced neuropathic pain |
| title_full | The involvement of the noradrenergic system in the antinociceptive effect of cucurbitacin D on mice with paclitaxel-induced neuropathic pain |
| title_fullStr | The involvement of the noradrenergic system in the antinociceptive effect of cucurbitacin D on mice with paclitaxel-induced neuropathic pain |
| title_full_unstemmed | The involvement of the noradrenergic system in the antinociceptive effect of cucurbitacin D on mice with paclitaxel-induced neuropathic pain |
| title_short | The involvement of the noradrenergic system in the antinociceptive effect of cucurbitacin D on mice with paclitaxel-induced neuropathic pain |
| title_sort | involvement of the noradrenergic system in the antinociceptive effect of cucurbitacin d on mice with paclitaxel induced neuropathic pain |
| topic | allodynia chemotherapy-induced neuropathic pain cucurbitacin B cucurbitacin D noradrenergic system paclitaxel |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1055264/full |
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