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Berberine Alleviates Paclitaxel-Induced Neuropathy

  • Rezaee, Ramin (Clinical Research Unit, Faculty of Medicine, Mashhad University of Medical Sciences) ;
  • Monemi, Alireza (Students research Committee, School of Medicine, North Khorasan University of Medical Sciences) ;
  • SadeghiBonjar, Mohammad Amin (Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences) ;
  • Hashemzaei, Mahmoud (Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences)
  • Received : 2018.01.10
  • Accepted : 2019.03.21
  • Published : 2019.06.28

Abstract

Objectives: Paclitaxel (PTX) as an anticancer drug used against solid cancers, possesses adverse reactions such as neuropathic pain which has confined its use. PTX-induced neuropathic pain is mediated via activation of oxidative stress. Berberine (BER), an isoquinoline phytochemical found in several plants, exerts strong antioxidant and painkilling properties. In the current study, we aimed to evaluate pain-relieving effect of BER in a mouse model of PTX-induced neuropathic pain. Methods: This study was done using 42 male albino mice that were randomly divided into 6 groups (n = 7) as follow: Sham-operated (not treated with PTX), negative control group (PTX-treated mice receiving normal saline), BER 5, 10, and 20 mg/kg (PTX-treated mice receiving BER) and positive control group (PTX-treated mice receiving imipramine 10 mg/kg). Neuropathic pain was induced by intraperitoneal administration of four doses of PTX (2 mg/kg/day) on days 1, 3, 5 and 7. Then, on day 7, hot plate test was done to assess latency to heat to measure possible anti-neuropathic pain effect of BER. Results: Four doses of PTX 2 mg/kg/day induced neuropathy that was reduced by BER at all time-points (i.e. 0, 30, 60, 90 and 120 min) after injection (P < 0.001 in comparison to control). The statistical analysis of data showed significant differences between groups (P < 0.001 in comparison to negative control), at 30, 60, 90 and 120 min after injection of BER 5, 10 and 20 mg/kg; in other words, 30, 60, 90 and 120 min after BER administration, neuropathic pain was significantly reduced as compared to normal saline-treated mice. Conclusion: Altogether, our results showed that PTX could induce neuropathic pain as reflected by hyperalgesia and BER could alleviate PTX-induced thermal hyperalgesia.

Keywords

berberine;paclitaxel;heat hyperalgesia;mice;neuropathic pain

DHOCBS_2019_v22n2_90_f0001.png 이미지

Figure 2 Chemical structure of BER.

DHOCBS_2019_v22n2_90_f0001.png 이미지

Figure 2 Chemical structure of BER.

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Figure 2 Effects of berberine (BER) on paclitaxel-induced neuropathic pain in mice. Latency to latency to heat was recorded at 0 (2B), 30 (2C), 60 (2D), 90 (2E) and 120(2F) min following treatment with B ER (*P < 0.05 and ***P < 0.001 represent significant differences compared to the negative control). Cont: negative control; BB: Berberine; and IM: Imipramine.

DHOCBS_2019_v22n2_90_f0002.png 이미지

Figure 2 Effects of berberine (BER) on paclitaxel-induced neuropathic pain in mice. Latency to latency to heat was recorded at 0 (2B), 30 (2C), 60 (2D), 90 (2E) and 120(2F) min following treatment with B ER (*P < 0.05 and ***P < 0.001 represent significant differences compared to the negative control). Cont: negative control; BB: Berberine; and IM: Imipramine.

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