An adenosine kinase inhibitor attenuates tactile allodynia in a rat model of diabetic neuropathic pain

Eur J Pharmacol. 1999 Jan 8;364(2-3):141-6. doi: 10.1016/s0014-2999(98)00840-1.

Abstract

The present study was conducted to characterize the development of tactile allodynia in the streptozotocin-induced rat model of diabetes, and to evaluate the antinociceptive effects of systemically administered morphine and the adenosine kinase inhibitor, 5'-deoxy-5-iodotubercidin (5'd-5IT) in this model. Rats were injected with 75 mg/kg streptozotocin (i.p.), and blood glucose levels were determined 3-4 weeks later. Diabetic (blood glucose levels > or = 250 mg/dl) and vehicle-injected rats were examined weekly for the development of tactile allodynia by measuring the threshold for hind paw withdrawal using von Frey hairs. Withdrawal thresholds were reduced to 6.8+/-0.6 g (mean+/-S.E.M.) in approximately one-third of streptozotocin-treated rats 7 weeks after streptozotocin treatment as compared to control thresholds (13.2+/-0.1 g), and this allodynia persisted for at least an additional 7 weeks. In additional experiments, morphine sulfate (5-21 micromol/kg, i.p.) produced dose-dependent antinociceptive effects on tactile allodynia for up to 2 h post-dosing. The adenosine kinase inhibitor, 5'd-5IT (2.5 and 5 micromol/kg, i.p.) also dose-dependently attenuated tactile allodynia. Pretreatment with the opioid receptor antagonist, naloxone (27 micromol/kg, i.p.) or the non-selective adenosine receptor antagonist, theophylline (111 micromol/kg, i.p.) significantly diminished the anti-allodynic effects of morphine and 5'd-5IT, respectively. The present study demonstrates that the potent and selective adenosine kinase inhibitor, 5'd-5IT, is equally effective as morphine in blocking tactile allodynia in this model.

MeSH terms

  • Adenosine Kinase / antagonists & inhibitors*
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / physiopathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Male
  • Morphine / pharmacology
  • Narcotics / pharmacology
  • Pain / drug therapy*
  • Pain / physiopathology
  • Pain Threshold / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin / pharmacology
  • Theophylline / pharmacology
  • Tubercidin / analogs & derivatives*
  • Tubercidin / pharmacology
  • Tubercidin / therapeutic use

Substances

  • 5'-deoxy-5-iodotubercidin
  • Anti-Bacterial Agents
  • Blood Glucose
  • Enzyme Inhibitors
  • Narcotics
  • Streptozocin
  • Morphine
  • Theophylline
  • Adenosine Kinase
  • Tubercidin