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

被引:2
作者
Toraman, Emine [1 ]
Bayram, Cemil [2 ]
Sezen, Selma [3 ]
Ozkaraca, Mustafa [4 ]
Hacimuftuoglu, Ahmet [5 ]
Budak, Harun [1 ]
机构
[1] Ataturk Univ, Sci Fac, Dept Mol Biol & Genet, TR-25240 Erzurum, Turkiye
[2] Ataturk Univ, Fac Vet Med, Dept Pharmacol & Toxicol, Erzurum, Turkiye
[3] Agri Ibrahim Cecen Univ, Fac Med, Dept Med Pharmacol, Agri, Turkiye
[4] Cumhuriyet Univ, Fac Vet Med, Dept Vet Pathol, Sivas, Turkiye
[5] Ataturk Univ, Fac Med, Dept Med Pharmacol, Erzurum, Turkiye
关键词
Parthenolide; Cancer; Paclitaxel-induced neuropathic pain; Paclitaxel; Expression; Bioinformatics; INDUCED PERIPHERAL NEUROPATHY; SENSORY NEUROPATHY; COLD HYPERALGESIA; CHANNELS; KINASE; CELLS; ACTIVATION; INHIBITION; IMPAIRMENT; DULOXETINE;
D O I
10.1007/s00210-023-02568-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:3707 / 3721
页数:15
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