The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain
Refractory peripheral neuropathy can occur as a side effect in 60–70% of patients receiving Paclitaxel (PTX). Yokukansan (YKS) is a Japanese herbal medicine reported to have analgesic properties for entrapment nerve injuries. Therefore, we investigated the anti-allodynic effect of Yokukansan on Pacl...
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MDPI AG
2024-02-01
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| Online Access: | https://www.mdpi.com/1648-9144/60/3/359 |
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| author | Hiroshi Yokomi Takahiro Kato Soshi Narasaki Satoshi Kamiya Shima Taguchi Yosuke T. Horikawa Yasuo M. Tsutsumi |
| author_facet | Hiroshi Yokomi Takahiro Kato Soshi Narasaki Satoshi Kamiya Shima Taguchi Yosuke T. Horikawa Yasuo M. Tsutsumi |
| author_sort | Hiroshi Yokomi |
| collection | DOAJ |
| description | Refractory peripheral neuropathy can occur as a side effect in 60–70% of patients receiving Paclitaxel (PTX). Yokukansan (YKS) is a Japanese herbal medicine reported to have analgesic properties for entrapment nerve injuries. Therefore, we investigated the anti-allodynic effect of Yokukansan on Paclitaxel-induced neuropathic pain. All experiments used 6-week-old male Sprague Dawley rats. Mechanical allodynia was evaluated using a dynamic plantar aesthesiometer. A mobile touch-stimulator unit applied progressively increasing force to the mid-plantar region of the hind paw in a vertical direction until the animal withdrew its paw. This was carried out before the Paclitaxel administration and during the first, second, third, and fourth weeks. Using a rat model of PTX-induced neuropathic pain (PTX rat), we injected PTX (intraperitoneally, 2 mg/kg) five times every 2 days. Using the dynamic plantar test, we evaluated the anti-allodynic effect of YKS (orally administered, 1 g/kg). YKS administration on a daily basis significantly enhanced the withdrawal threshold in PTX rats and reduced the expression level of activated microglia immunostaining with Iba1, a specific marker for microglia. The intrathecal administration of WAY-100635 (5-hydroxytryptamine [5-HT]<sub>1A</sub> receptor antagonist) and Ketanserin (5-HT<sub>2A/2C</sub> receptor antagonist) inhibited the protective effects of YKS. YKS exhibited an anti-allodynic effect in a rodent model of PTX-induced neuropathic pain by reducing the sensitivity to pain stimuli. These results suggest that Yokukansan may activate 5-HT receptors in the spinal cord, mediating Paclitaxel-induced neuropathic pain. |
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| publishDate | 2024-02-01 |
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| series | Medicina |
| spelling | doaj.art-b8f4d49d4a3545478e6dcee6d8fdd95b2024-03-27T13:53:24ZengMDPI AGMedicina1010-660X1648-91442024-02-0160335910.3390/medicina60030359The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic PainHiroshi Yokomi0Takahiro Kato1Soshi Narasaki2Satoshi Kamiya3Shima Taguchi4Yosuke T. Horikawa5Yasuo M. Tsutsumi6Department of Anesthesiology and Critical Care, Hiroshima University Hospital, Hiroshima 734-8551, JapanDepartment of Anesthesiology and Critical Care, Hiroshima University Hospital, Hiroshima 734-8551, JapanDepartment of Anesthesiology and Critical Care, Hiroshima University Hospital, Hiroshima 734-8551, JapanDepartment of Anesthesiology and Critical Care, Hiroshima University Hospital, Hiroshima 734-8551, JapanDepartment of Anesthesiology and Critical Care, Hiroshima University Hospital, Hiroshima 734-8551, JapanDepartment of Anesthesiology and Critical Care, Hiroshima University Hospital, Hiroshima 734-8551, JapanDepartment of Anesthesiology and Critical Care, Hiroshima University Hospital, Hiroshima 734-8551, JapanRefractory peripheral neuropathy can occur as a side effect in 60–70% of patients receiving Paclitaxel (PTX). Yokukansan (YKS) is a Japanese herbal medicine reported to have analgesic properties for entrapment nerve injuries. Therefore, we investigated the anti-allodynic effect of Yokukansan on Paclitaxel-induced neuropathic pain. All experiments used 6-week-old male Sprague Dawley rats. Mechanical allodynia was evaluated using a dynamic plantar aesthesiometer. A mobile touch-stimulator unit applied progressively increasing force to the mid-plantar region of the hind paw in a vertical direction until the animal withdrew its paw. This was carried out before the Paclitaxel administration and during the first, second, third, and fourth weeks. Using a rat model of PTX-induced neuropathic pain (PTX rat), we injected PTX (intraperitoneally, 2 mg/kg) five times every 2 days. Using the dynamic plantar test, we evaluated the anti-allodynic effect of YKS (orally administered, 1 g/kg). YKS administration on a daily basis significantly enhanced the withdrawal threshold in PTX rats and reduced the expression level of activated microglia immunostaining with Iba1, a specific marker for microglia. The intrathecal administration of WAY-100635 (5-hydroxytryptamine [5-HT]<sub>1A</sub> receptor antagonist) and Ketanserin (5-HT<sub>2A/2C</sub> receptor antagonist) inhibited the protective effects of YKS. YKS exhibited an anti-allodynic effect in a rodent model of PTX-induced neuropathic pain by reducing the sensitivity to pain stimuli. These results suggest that Yokukansan may activate 5-HT receptors in the spinal cord, mediating Paclitaxel-induced neuropathic pain.https://www.mdpi.com/1648-9144/60/3/359YokukansanPaclitaxel5-HT receptorneuropathic pain |
| spellingShingle | Hiroshi Yokomi Takahiro Kato Soshi Narasaki Satoshi Kamiya Shima Taguchi Yosuke T. Horikawa Yasuo M. Tsutsumi The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain Medicina Yokukansan Paclitaxel 5-HT receptor neuropathic pain |
| title | The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain |
| title_full | The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain |
| title_fullStr | The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain |
| title_full_unstemmed | The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain |
| title_short | The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain |
| title_sort | serotonin mediated anti allodynic effect of yokukansan on paclitaxel induced neuropathic pain |
| topic | Yokukansan Paclitaxel 5-HT receptor neuropathic pain |
| url | https://www.mdpi.com/1648-9144/60/3/359 |
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