Abstract
Pacliatxel is a taxol-based chemotherapeutic drug that is widely used to treat cancer. However, it can also induce peripheral neuropathy, which limits its use. Although several drugs are prescribed to attenuate neuropathies, no optimal treatment is available. Thus, in our study, we analyzed whether SH003 and its sub-components could alleviate paclitaxel-induced neuropathic pain. Multiple paclitaxel injections (cumulative dose 8 mg/kg, i.p.) induced cold and mechanical allodynia from day 10 to day 21 after the first injection in mice. Oral administration of SH003, an herbal mixture extract of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz (Tk), dose-dependently attenuated both allodynia. However, when administered separately only Tk decreased both allodynia. The effect of Tk was shown to be mediated by the spinal noradrenergic system as intrathecal pretreatment with α1- and α2-adrenergic-receptor antagonists (prazosin and idazoxan), but not 5-HT1/2, and 5-HT3-receptor antagonists (methysergide and MDL-72222) blocked the effect of Tk. The spinal noradrenaline levels were also upregulated. Among the phytochemicals of Tk, cucurbitacin D was shown to play a major role, as 0.025 mg/kg (i.p.) of cucurbitacin D alleviated allodynia similar to 500 mg/kg of SH003. These results suggest that Tk should be considered when treating paclitaxel-induced neuropathic pain.
Highlights
Paclitaxel, from the bark of Taxus brevifolia, is a widely used anti-cancer drug that has been used to treat breast, ovarian, and lung cancer [1,2,3]
In paclitaxel-induced neuropathic pain, modulating the serotonergic and noradrenergic systems could be an effective way to alleviate the severe cold and mechanical allodynia induced by paclitaxel injection
As only Trichosanthes kirilowii Maximowicz (Tk) was effective against both cold and mechanical allodynia induced by paclitaxel, subsequent experiments were conducted using Tk
Summary
Paclitaxel, from the bark of Taxus brevifolia, is a widely used anti-cancer drug that has been used to treat breast, ovarian, and lung cancer [1,2,3]. Despite its well-known anti-cancer efficacy, the use of paclitaxel may be limited due to a severe dose-limiting factor, which is peripheral neuropathic pain [4]. It has been reported that within 24 h of its first administration, neuropathic pain occurs, characterized by cold and mechanical allodynia and numbness in the extremities [5,6]. This dose-limiting side effect may prevent the continuation of chemotherapy and reduce the patient’s quality of life [7]. A drug that can effectively alleviate chemotherapy-induced neuropathic pain (CIPN) is critically needed [11]
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