5,7-Dimethoxycoumarin ameliorates vincristine induced neuropathic pain: potential role of 5HT3 receptors and monoamines

This study was designed to investigate the possible analgesic and antiallodynic effects of 5,7-DMC in a murine model of VINP. Vincristine was administered to groups of BALB/c male mice (0.1 mg/kg intraperitoneally) once daily for 14 days to induce VINP. Thermal hyperalgesia and mechanical allodynia were quantified using the tail immersion test and von Frey filament application method. The levels of monoamine neurotransmitters and vitamin C in frontal cortical, striatal and hippocampal tissues, as well as the TNF-α level in plasma, were quantified using high performance liquid chromatography and ELISA respectively. On day 15 of the protocol, acute treatment with 5,7-DMC clearly reversed VINP thermal hyperalgesia, mechanical static allodynia, mechanical dynamic allodynia, and cold allodynia. The activity of 5,7-DMC against hyperalgesia and allodynia was inhibited by pretreatment with ondansetron but not naloxone, implicating a 5-HT3 receptor involvement. VINP vitamin C levels were restored by 5,7-DMC in the frontal cortex, and changes in serotonin, dopamine, adenosine, inosine and hypoxanthine levels caused by vincristine were reversed either fully or partially. Additionally, the vincristine-induced rise in hippocampal serotonin, dopamine, inosine and striatal serotonin was appreciably reversed by 5,7-DMC. 5,7-DMC also reversed the vincristine-induced increase in the plasma level of TNF-α. In negating the changes in the levels of some neurotransmitters in the brain caused b...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research