JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice
Oxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of <i>Aconitum carmichaelii</i>, <i>Angelica gigas</i>, and <i>Zingiber officinale</i...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8811 |
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| author | Ji Hwan Lee Hyunseung Ji Seong-Gyu Ko Woojin Kim |
| author_facet | Ji Hwan Lee Hyunseung Ji Seong-Gyu Ko Woojin Kim |
| author_sort | Ji Hwan Lee |
| collection | DOAJ |
| description | Oxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of <i>Aconitum carmichaelii</i>, <i>Angelica gigas</i>, and <i>Zingiber officinale</i>. Its anti-tumor effect has been reported; however, the efficacy of JI017 against oxaliplatin-induced allodynia has never been explored. Single oxaliplatin injection [6 mg/kg, intraperitoneal, (i.p.)] induced both cold and mechanical allodynia, and oral administration of JI017 (500 mg/kg) alleviated cold but not mechanical allodynia in mice. Real-time polymerase chain reaction (PCR) analysis demonstrated that the upregulation of mRNA of spinal transient receptor potential vanilloid 1 (TRPV1) and astrocytes following oxaliplatin injection was downregulated after JI017 treatment. Moreover, TRPV1 expression and the activation of astrocytes were intensely increased in the superficial area of the spinal dorsal horn after oxaliplatin treatment, whereas JI017 suppressed both. The administration of TRPV1 antagonist [capsazepine, intrathecal (i.t.), 10 μg] attenuated the activation of astrocytes in the dorsal horn, demonstrating that the functions of spinal TRPV1 and astrocytes are closely related in oxaliplatin-induced neuropathic pain. Altogether, these results suggest that JI017 may be a potent candidate for the management of oxaliplatin-induced neuropathy as it decreases pain, spinal TRPV1, and astrocyte activation. |
| first_indexed | 2024-03-10T08:44:29Z |
| format | Article |
| id | doaj.art-05f02063a94e48aa991970df51fe4f14 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:44:29Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-05f02063a94e48aa991970df51fe4f142023-11-22T08:00:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216881110.3390/ijms22168811JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in MiceJi Hwan Lee0Hyunseung Ji1Seong-Gyu Ko2Woojin Kim3Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaDepartment of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, KoreaKorean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaDepartment of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, KoreaOxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of <i>Aconitum carmichaelii</i>, <i>Angelica gigas</i>, and <i>Zingiber officinale</i>. Its anti-tumor effect has been reported; however, the efficacy of JI017 against oxaliplatin-induced allodynia has never been explored. Single oxaliplatin injection [6 mg/kg, intraperitoneal, (i.p.)] induced both cold and mechanical allodynia, and oral administration of JI017 (500 mg/kg) alleviated cold but not mechanical allodynia in mice. Real-time polymerase chain reaction (PCR) analysis demonstrated that the upregulation of mRNA of spinal transient receptor potential vanilloid 1 (TRPV1) and astrocytes following oxaliplatin injection was downregulated after JI017 treatment. Moreover, TRPV1 expression and the activation of astrocytes were intensely increased in the superficial area of the spinal dorsal horn after oxaliplatin treatment, whereas JI017 suppressed both. The administration of TRPV1 antagonist [capsazepine, intrathecal (i.t.), 10 μg] attenuated the activation of astrocytes in the dorsal horn, demonstrating that the functions of spinal TRPV1 and astrocytes are closely related in oxaliplatin-induced neuropathic pain. Altogether, these results suggest that JI017 may be a potent candidate for the management of oxaliplatin-induced neuropathy as it decreases pain, spinal TRPV1, and astrocyte activation.https://www.mdpi.com/1422-0067/22/16/8811allodyniaastrocyteJI017medicinal herbsoxaliplatinTRPV1 |
| spellingShingle | Ji Hwan Lee Hyunseung Ji Seong-Gyu Ko Woojin Kim JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice International Journal of Molecular Sciences allodynia astrocyte JI017 medicinal herbs oxaliplatin TRPV1 |
| title | JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice |
| title_full | JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice |
| title_fullStr | JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice |
| title_full_unstemmed | JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice |
| title_short | JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice |
| title_sort | ji017 attenuates oxaliplatin induced cold allodynia via spinal trpv1 and astrocytes inhibition in mice |
| topic | allodynia astrocyte JI017 medicinal herbs oxaliplatin TRPV1 |
| url | https://www.mdpi.com/1422-0067/22/16/8811 |
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