Analgesic potential of intrathecal farnesyl thiosalicylic acid and GW 5074 in vincristine-induced neuropathic pain in rats.
Ras and c-Raf constitute an important part of mitogen-activated protein (MAP) kinase family as Ras/Raf/MEK/ERK2 signaling cascade and the role of MAP kinases has been well defined in neuropathic pain. The present study investigates the analgesic potential of farnesyl thiosalicylic acid, a novel Ras inhibitor, and GW 5074, a selective c-Raf1 inhibitor, in vincristine-induced neuropathic pain. Peripheral neuropathy was induced in rats by administering vincristine (50 μg/kg i.p.) for 10 consecutive days. Pain development was assessed on 14th day in terms of cold allodynia; mechanical hyperalgesia and mechanical allodynia by performing acetone test, pin-prick and von frey tests, respectively. Farnesyl thiosalicylic acid and GW 5074 were injected intrathecally on 14th day following vincristine administration. Administration of vincristine produced significant neuropathic pain manifestations in terms of cold and mechanical allodynia, and mechanical hyperalgesia. Single intrathecal administration of farnesyl thiosalicylic acid (5 and 10 μg) as well as GW 5074 (2 and 4 μg) significantly attenuated vincristine-induced hyperalgesia and allodynia. The analgesic effects of farnesyl thiosalicylic acid and GW 5074 in vincristine model suggests that pharmacological inhibition of Ras and c-Raf-1 signalling may be potentially useful for managing neuropathic pain.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
Amteshwar Singh
AS
Jaggi
Nirmal
N
Singh
D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D005204:Farnesol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007278:Injections, Spinal; D008297:Male; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy*; D010636:Phenols / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000494:pharmacology / Q000627:therapeutic use*; D014750:Vincristine / Q000633:toxicity*
D000700:Analgesics; D007211:Indoles; D010636:Phenols; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D005204:Farnesol; D014750:Vincristine; C489251:5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone