title: Anti-nociceptive and anti-allodynic activity of aliskiren in various pain models.
abstract: In the present study, we have investigated the anti-nociceptive and anti-allodynic activity of the renin inhibitor, aliskiren, in various pain models. The anti-nociceptive activity of aliskiren was investigated in chemically-induced pain, orofacial pain and centrally mediated pain models. Anti-allodynic activity was evaluated in post-operative and neuropathic pain models. The levels of TNF-α and IL-6 were measured in homogenates of hind paw as markers of inflammation in formalin injected mice. Intraperitoneal administration of aliskiren (1-50mg/kg) showed anti-nociceptive activity in the writhing test, formalin hind paw test, capsaicin induced pain, and orofacial pain tests in ICR mice in a dose dependent manner. Aliskiren (50mg/kg, i.p.) reduced levels of TNF-α and IL-6 in hind paw homogenates of formalin-injected mice. Aliskiren (50mg/kg, i.p.) did not show any analgesic activity in hot-plate and tail-flick tests, indicating the absence of centrally mediated anti-nociceptive effects. On the other hand, intra-plantar administration of aliskiren (0.1, 0.5 and 1mg) showed analgesic activity in rat formalin tests, indicating a locally mediated effect. Aliskiren (30-100mg/kg, i.p.) showed anti-allodynic activity in post-operative pain and chronic constriction injury-induced neuropathic pain in Sprague Dawley rats. This data suggests that aliskiren may have the potential to be used as an anti-nociceptive and anti-allodynic agent.
authors.affiliation: Department of Pharmacology, Zydus Research Center, Sarkhej-Bavla National Highway-8A, Moraiya, Ahmedabad 382 213, Gujarat, India.
authors.forename: Rakesh B
authors.initials: RB
authors.lastname: Patel
authors.forename: Vishwanath D
authors.initials: VD
authors.lastname: Pawar
authors.forename: Kanaiyalal D
authors.initials: KD
authors.lastname: Prajapati
authors.forename: Bhavin M
authors.initials: BM
authors.lastname: Sonara
authors.forename: Shrikalp S
authors.initials: SS
authors.lastname: Deshpande
authors.forename: Gaurang B
authors.initials: GB
authors.lastname: Shah
authors.forename: Mukul R
authors.initials: MR
authors.lastname: Jain
mesh_terms: D019342:Acetic Acid; D000577:Amides / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal; D002211:Capsaicin; D005260:Female; D005557:Formaldehyde; D005650:Fumarates / Q000627:therapeutic use*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000577:Amides; D000700:Analgesics; D005650:Fumarates; D005557:Formaldehyde; C446481:aliskiren; D019342:Acetic Acid; D002211:Capsaicin