title: Intrathecal delivery of farnesyl thiosalicylic acid and GW 5074 attenuates hyperalgesia and allodynia in chronic constriction injury-induced neuropathic pain in rats.
abstract: The role of mitogen-activated protein kinase (MAPK) family has been well defined in neuropathic pain. Ras and c-Raf constitute an important part of MAP kinase family as Ras/Raf/MEK/ERK2 signaling cascade. The present study was designed to investigate the analgesic potential of farnesyl thiosalicylic acid, a novel Ras inhibitor, and GW 5074, a selective c-Raf1 inhibitor, in chronic constriction-induced injury (CCI)-induced peripheral neuropathic pain. Neuropathic pain was induced by placing four loose ligatures around the sciatic nerve. The development of pain was assessed on 14th day in terms of cold allodynia; mechanical hyperalgesia and mechanical allodynia by performing acetone test, pinprick and Von Frey tests, respectively. Farnesyl thiosalicylic acid (2.5, 5 and 10 μg) and GW 5074 (1, 2 and 4 μg) were injected intrathecally on 14th day following nerve ligature to assess their analgesic potential in CCI model. Nerve ligature-induced CCI 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 CCI-induced hyperalgesia and allodynia. The analgesic effects of farnesyl thiosalicylic acid and GW 5074 in CCI model suggests that pharmacological inhibition of Ras and c-Raf-1 signaling may be potentially useful for managing neuropathic pain.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002 Punjab, India.
authors.forename: Amteshwar Singh
authors.initials: AS
authors.lastname: Jaggi
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D003251:Constriction, Pathologic / Q000150:complications; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology*; D007211:Indoles / Q000008:administration & dosage*; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage*; D011106:Polyisoprenyl Phosphates / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012585:Sciatica / Q000150:complications* / Q000209:etiology
chemical_list: D000700:Analgesics; D007211:Indoles; D010636:Phenols; D011106:Polyisoprenyl Phosphates; C502746:farnesyl thiopyrophosphate; C489251:5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone