title: Systemic and spinal administration of etanercept, a tumor necrosis factor alpha inhibitor, blocks tactile allodynia in diabetic mice.
abstract: Painful diabetic neuropathy is one of the most common forms of neuropathic pain syndromes. Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated as a key pain mediator in the development and maintenance of neuropathic pain conditions. Recent studies showed that endogenous TNF-alpha production was also accelerated in neural tissues and spinal cord under chronic hyperglycemia. Thus, in this study, we investigated whether pharmacological inhibition of TNF-alpha by etanercept, a TNF-alpha antagonist, could block behavioral sign of diabetic neuropathic pain. Diabetes was induced by streptozotocin (STZ) (200 mg/kg, i.p.) in Balb-c mice and behavioral tests were performed between 45 and 60 days after STZ administration. Mechanical and thermal sensitivities were measured by a series of calibrated Von Frey filaments and hot plate test, respectively. Etanercept was given by either intravenous (i.v.), intrathecal (i.th.) or intraplantar (i.pl.) routes to the diabetic mice. Tactile allodynia, but not thermal hyperalgesia, developed in diabetic mice. Both i.v. (1, 10 and 20 mg/kg) or i.th. (1, 5 and 10 μg/mouse) treatments with etanercept produced dose dependent reversal of tactile allodynia in diabetic mice. However, etanercept was found to be inactive against allodynia when given i.pl. (1, 5 and 10 μg/mouse). Our results suggest that etanercept has promising effects on diabetic neuropathic pain with antiallodynic effects when given systemically or intrathecally.
authors.affiliation: Department of Pharmacology, Gulhane Military Academy of Medicine, Etlik, Ankara, Turkey. dogrula@gata.edu.tr
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogrul
authors.forename: Husamettin
authors.initials: H
authors.lastname: Gul
authors.forename: Ozgur
authors.initials: O
authors.lastname: Yesilyurt
authors.forename: Umit H
authors.initials: UH
authors.lastname: Ulas
authors.forename: Oguzhan
authors.initials: O
authors.lastname: Yildiz
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept; D005260:Female; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007275:Injections, Intravenous; D007278:Injections, Spinal; D051379:Mice; D008807:Mice, Inbred BALB C; D011930:Reaction Time / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D013311:Streptozocin; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D013311:Streptozocin; D000068800:Etanercept