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

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≥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 μmol/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 μmol/kg, i.p.) also dose-dependently attenuated tactile allodynia. Pretreatment with the opioid receptor antagonist, naloxone (27 μmol/kg, i.p.) or the non-selective adenosine receptor antagonist, theophylline (111 μmol/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.