Influence of dosing times on cisplatin-induced peripheral neuropathy in rats

Abstract

BackgroundAlthough cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats.MethodsCDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague–Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed.ResultsIn order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia.ConclusionsIt was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2777-0) contains supplementary material, which is available to authorized users.

Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation

“…However, tail flick latencies of these rats are significantly increased post-chemotherapy (p < 0.05 vs pre-CIPN) indicating cisplatin-induced heat hypoalgesia (Fig. 5D1 and D2) (Han et al, 2014; Hopkins et al, 2016; Seto et al, 2016). Since PrNMI is equally effective in male and female CIPN rats, we continued all subsequent experiments with male rats.…”

May a sigma‐1 antagonist improve neuropathic signs induced by cisplatin and vincristine in rats?

“…Mechanical hyperalgesia or the absence of hyperalgesia, or even hyposensitivity, was previously described (Authier et al., ; Cata, Weng, & Dougherty, ; Seto et al., ) after CIS administration and the differences were attributed to a different degree of neural peripheral damage. We did not find any modification in response to mechanical noxious stimulation in rats treated with CIS, suggesting that peripheral neural damage induced by CIS in our conditions was not severe.…”

N-acetylcysteine versus progesterone on the cisplatin-induced peripheral neurotoxicity

“…The used vehicle was sterile saline. The rats were injected at a dose of 2 mg/kg/twice weekly/4 weeks intraperitoneally [31,49]. The neurotoxicity induced by such dose is related to the direct effect of cisplatin and is not secondary to modulation of the drug nephrotoxicity [31].…”