Protective effects of anandamide against cisplatin-induced peripheral neuropathy in rats.

Background/aim Cisplatin (CIS) is an effective antineoplastic agent used in the treatment of several cancer types. Peripheral neuropathy is a major dose-limiting side-effect in cisplatin therapy. Cannabinoids may alleviate this painful side effect. This study investigated the analgesic effects of anandamide (AN) on CIS-induced peripheral neuropathy, in vitro effects of AN in CIS neurotoxicity and influence of nitric oxide (NO) in this effect. Materials and methods This study is an experimental animal study. Primary DRG cultures were prepared from one day old rats for in vitro investigations. DRG cells were incubated with CIS (100-300 mM), and AN (10, 50, 100 and 500 mikroM) was administered with the submaximal concentration of CIS. Female Sprague Dawley rats were divided into Control, CIS, CIS+AN, CIS+AN+ L-NG-nitro arginine methyl ester (L-NAME). CIS was administered 3 mg/kg ip once weekly for five weeks. AN (1 mg/kg ip) or in combination with 10 mg/kg ip L-NAME was administrated 30 min before CIS injection. Mechanical allodynia, thermal hyperalgesia and tail clip tests were performed. After intracardiac perfusion, sciatic nerves (SN) and dorsal root ganglia (DRG) were isolated and semi-thin sections were stained with toluidine blue and investigated histologically.SPSS21.0 and Sigma STAT 3.5 were used for statistical analysis. One/two way ANOVA, Kruskal Wallis, and Wilcoxon Signed Ranks tests were used. A p-value of 0.05 was accepted as significant. Results Cisplatin caused significant mechanical allodynia. AN and AN+L-NAME significantly increased hind paw withdrawal latency in mechanical allodynia test. The degenerated axons significantly increased in cisplatin group, anandamide decreased this effect. The frequency of larger neurons seems to be higher in CIS+AN group. Conclusion Anandamide may be a therapeutic alternative for the treatment of cisplatin-induced peripheral neuropathy however its central adverse effects must be considered.