Abstract
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 Aconitum carmichaelii, Angelica gigas, and Zingiber officinale. 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.
Highlights
Oxaliplatin has been widely used and recommended as a first-line treatment for metastatic colorectal cancer [1,2]
We investigated whether JI017 attenuates oxaliplatin-induced neuropathic pain
In previous studies [36,42,43], a mouse model of cold and mechanical allodynia induced with a single injection of oxaliplatin was used to investigate the efficacy of JI017, a formula of medicinal herbs, and the mechanisms of its analgesic effect
Summary
Oxaliplatin has been widely used and recommended as a first-line treatment for metastatic colorectal cancer [1,2]. The clinical efficacy of oxaliplatin is better than that of previously used drugs, such as cisplatin [3]. Despite its anti-tumor efficacy, the doselimiting toxicity of oxaliplatin limits its use [4,5]. About 90% of oxaliplatin-treated patients suffered acute pain, which can be initiated only 24 h after a single injection of oxaliplatin [6]. Cold and mechanical allodynia are common occurring symptoms in animal models of oxaliplatin-induced neuropathic pain [7,8]. No optimal drug, without any side effects, has been developed, and the underlying mechanisms of this neuropathy still need to be elucidated [9]
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