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

Abstract

Background/aim: Cisplatin (CIS) is an effective antineoplastic agent used in treatment of several cancer types. Peripheral neuropathy is a major dose-limiting side-effect in CIS 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 is an experimental animal study. Primary dorsal root ganglion (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 μM) 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 (LNAME). CIS was administered 3 mg/kg i.p once weekly for five weeks. AN (1 mg/kg i.p) or in combination with 10 mg/kg i.p LNAME was administrated 30 min before CIS injection. Mechanical allodynia, thermal hyperalgesia and tail clip tests were performed. After intracardiac perfusion, sciatic nerves (SN) and DRGs were isolated and semi-thin sections were stained with toluidine blue and investigated histologically. SPSS 21.0 and Sigma STAT 3.5 were used for statistical analysis.One/two way ANOVA, Kruskal Wallis, and Wicoxon Signed Ranks tests were used. A p-value of 0.05 was accepted as significant.Results: CIS caused significant mechanical allodynia. AN and AN+LNAME significantly increased hind paw withdrawal latency in mechanical allodynia test. The degenerated axons significantly increased in CIS group, while decreased in AN group. The frequency of larger neurons seems to be higher in CIS+AN group. Conclusion:AN may be a therapeutic alternative for the treatment of CIS-induced peripheral neuropathy, however its central adverse effects must be considered.

Effect of the Cannabinoid Agonist WIN 55,212-2 on Neuropathic and Visceral Pain Induced by a Non-Diarrheagenic Dose of the Antitumoral Drug 5-Fluorouracil in the Rat

“…In a previous work performed in rats, the non-selective cannabinoid agonist WIN 55,212-2 (WIN) at a non-psychotropic dose partly attenuated 5-FU-induced diarrhea, but did not counteract the associated mucositis [30]. Interestingly, this and other cannabinoids may improve peripheral tactile neuropathy induced by different antitumoral drugs in rodents, including cisplatin, paclitaxel, vincristine and oxaliplatin [31][32][33][34][35][36][37]. However, their effects on the alterations of somatic and visceral sensitivity that 5-FU may cause have not yet been studied.…”