title: Possible mechanism of protective effect of thalidomide in STZ-induced-neuropathic pain behavior in rats.
abstract: BACKGROUND
  Diabetes-induced neuropathic pain is recognized as one of the most difficult type of pain to treat and conventional analgesics are well known to be partially effective or associated with potential toxicity. Recently, it has been demonstrated that thalidomide, besides its teratogenic potential, reduced chronic pain in an SNL experimental pain model.
  
  
  OBJECTIVE
  The present study was designed to investigate the effect of thalidomide on streptozotocin (STZ)-induced neuropathic pain in rats.
  
  
  METHODS
  Streptozotocin (20 mg/kg, i.p, daily × 4 days) was administered to induce diabetes in the rats. Nociceptive latency was measured using tail-flick and paw-withdrawal test. Thermal hyperalgesia and mechanical allodynia were measured using planter test and dynamic aesthesiometer (Ugo-Basile, Italy), respectively. Urinary and serum nitrite concentration was estimated using Greiss reagent method. Spleen homogenate supernatant was prepared from spleen of 28th day diabetic rats and administered to normal rats (400 ul, i.v) daily for 28 days.
  
  
  RESULTS
  Pain threshold progressively decreased in STZ-treated rats, as compared with control rats. 3 weeks after induction of diabetes, the rat exhibited thermal hyperalgesia and mechanical allodynia. The analgesic effect of morphine (8 mg/kg, s.c.) was significantly decreased in both diabetic and in SHS-treated non-diabetic rats. Administration of thalidomide (25 and 50 mg/kg, i.p), a TNF-α inhibitor, significantly prevented hyperglycemia-induced thermal hyperalgesia and mechanical allodynia and also attenuated the increase in serum and urinary nitrite concentration, as compared with untreated diabetic rats. Also, thalidomide (25 and 50 mg/kg, i.p) 1 h before or concurrently with morphine significantly restored the analgesic effect of morphine in diabetic rats.
  
  
  CONCLUSIONS
  It may be concluded that thalidomide has a beneficial effect in neuropathic pain by decreasing cytokines (TNF-α) and nitric oxide level and may provide a novel promising therapeutic approach for managing painful diabetic neuropathy.
authors.affiliation: I.S.F College of Pharmacy-Moga, Moga, Punjab, India. taliyanraja@gmail.com
authors.forename: Rajeev
authors.initials: R
authors.lastname: Taliyan
authors.forename: Pyare Lal
authors.initials: PL
authors.lastname: Sharma
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006930:Hyperalgesia / Q000209:etiology / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D009437:Neuralgia / Q000209:etiology / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D009573:Nitrites / Q000097:blood / Q000652:urine; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013156:Splenectomy; D013311:Streptozocin / Q000494:pharmacology; D013792:Thalidomide / Q000008:administration & dosage / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000701:Analgesics, Opioid; D001786:Blood Glucose; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D013311:Streptozocin; D009020:Morphine