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Parthenolide as a potential analgesic in the treatment of paclitaxel-induced neuropathic pain: the rat modeling

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Abstract

In this study, we determined the therapeutic effect of parthenolide (PTL), the active component of Tanacetum parthenium, on neuropathic pain caused by paclitaxel (PTX), a chemotherapeutic drug frequently used in cancer treatment, at the gene and protein levels. To this end, 6 groups were formed: control, PTX, sham, 1 mg/PTL, 2 mg/kg PTL, and 4 mg/kg PTL. Pain formation was tested by Randall-Selitto analgesiometry and locomotor activity behavioral analysis. Then, PTL treatment was performed for 14 days. After the last dose of PTL was taken, Hcn2, Trpa1, Scn9a, and Kcns1 gene expressions were measured in rat brain (cerebral cortex/CTX) tissues. In addition, changes in the levels of SCN9A and KCNS1 proteins were determined by immunohistochemical analysis. Histopathological hematoxylin-eosin staining was also performed to investigate the effect of PTL in treating tissue damage on neuropathic pain caused by PTX treatment. When the obtained data were analyzed, pain threshold and locomotor activity decreased in PTX and sham groups and increased with PTL treatment. In addition, it was observed that the expression of the Hcn2, Trpa1, and Scn9a genes decreased while the Kcns1 gene expression increased. When protein levels were examined, it was determined that SCN9A protein expression decreased and the KCNS1 protein level increased. It was determined that PTL treatment also improved PTX-induced tissue damage. The results of this study demonstrate that non-opioid PTL is an effective therapeutic agent in the treatment of chemotherapy-induced neuropathic pain, especially when used at a dose of 4 mg/kg acting on sodium and potassium channels.

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Data availability

The data supporting the findings of the present research are available on request from the corresponding author upon reasonable request.

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Funding

Financial support for the present research was received from Atatürk University Scientific Research Projects Coordination Commission [Grant Number: FDK-2020-8345].

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Authors and Affiliations

  1. Science Faculty, Department of Molecular Biology and Genetics, Atatürk University, 25240, Erzurum, Türkiye

    Emine Toraman & Harun Budak

  2. Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, Atatürk University, Erzurum, Türkiye

    Cemil Bayram

  3. Faculty of Medicine, Department of Medical Pharmacology, Ağrı İbrahim Çeçen University, Ağrı, Türkiye

    Selma Sezen

  4. Faculty of Veterinary Medicine, Department of Veterinary Pathology, Cumhuriyet University, Sivas, Türkiye

    Mustafa Özkaraca

  5. Faculty of Medicine, Department of Medical Pharmacology, Atatürk University, Erzurum, Türkiye

    Ahmet Hacımüftüoğlu

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Contributions

Conceived and designed the experiments: HB (group leader), ET and AH. Performed the experiments: ET, CB, SS and MÖ. Analyzed the data: ET, CB and MÖ. Contributing reagents/materials/analysis tools: HB. Wrote the paper: HB, ET and MÖ. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Harun Budak.

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Ethical approval

With the decision no. 193 of Atatürk University Animal Experiments Local Ethics Committee (AUHADYEK) in its session dated 07.11.2019 and numbered 14, all stages of our study were approved to comply with ethical rules.

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Toraman, E., Bayram, C., Sezen, S. et al. Parthenolide as a potential analgesic in the treatment of paclitaxel-induced neuropathic pain: the rat modeling. Naunyn-Schmiedeberg's Arch Pharmacol 396, 3707–3721 (2023). https://doi.org/10.1007/s00210-023-02568-5

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  • DOI: https://doi.org/10.1007/s00210-023-02568-5

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