title: Effect of dipyrone and thalidomide alone and in combination on STZ-induced diabetic neuropathic pain.
abstract: Diabetic neuropathy is recognized as one of the most common complications of chronic diabetes, but its pathophysiological mechanism is complex and yet to be completely explored. Monotherapy with conventional analgesics fails to provide adequate pain relief in peripheral diabetic neuropathy. There are a number of evidence suggesting that tumor necrosis factor (TNF-α) plays an important role in the pathogenesis of peripheral diabetic neuropathy. TNF-α up-regulation activates nuclear factor κB, which further up-regulates cyclooxygenase (COX)-2 leading to altered prostaglandin profile. Inhibition of TNF-α and COX-2 provides beneficial effect on diabetic neuropathy by decreasing the oxidative stress level and by preventing neuronal hypersensitivity due to an increased prostaglandin level. The present study was designed to assess the effect of dipyrone and thalidomide on streptozotocin (STZ)-induced neuropathic pain behavior in rats. STZ 50 mg/kg, i.p. was administered to induce experimental diabetes in the rats. Three weeks following STZ, dipyrone (300 and 600 mg/kg, i.p.) and thalidomide (25 and 50 mg/kg, i.p.) alone and subeffective dose combination of dipyrone and thalidomide (300 and 25 mg/kg(-1), i.p.) administered daily for 2 weeks significantly attenuated thermal hyperalgesia, mechanical allodynia, and formalin-induced phase-2 flinching response. Moreover, the subeffective dose combination of dipyrone and thalidomide and preemptive treatment with thalidomide (50 mg/kg) reduces oxidative stress in diabetic rats. In conclusion, the combination of subeffective dose of dipyrone and thalidomide prevented the development and maintenance of experimental diabetic neuropathy. The combination of thalidomide (TNF-α inhibitor) and dipyrone (COX inhibitor) may be used as a potential therapeutic agent for the treatment of diabetic neuropathy.
authors.affiliation: Department of Pharmacology, I.S.F College of Pharmacy, Moga, 142001, Punjab, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Chauhan
authors.forename: Rajeev
authors.initials: R
authors.lastname: Taliyan
authors.forename: Pyare Lal
authors.initials: PL
authors.lastname: Sharma
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D004177:Dipyrone / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D001786:Blood Glucose; D004338:Drug Combinations; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D013792:Thalidomide; D004177:Dipyrone; D005978:Glutathione