An adenosine kinase inhibitor attenuates tactile allodynia in a rat model of diabetic neuropathic pain |
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| Institution: | 1. Department of Pharmacology, Wroclaw Medical University, Wrocław, Poland;2. Department of Endocrinology, Diabetology and Isotopes Therapy, Wroclaw Medical University, Wrocław, Poland;3. Department of Epizootiology and Clinic of Birds and Exotic Animals, The Faculty of Veterinary Medicine, University of Environmental and Life Sciences, Wrocław, Poland;4. Division of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wrocław, Poland;5. Division of Biomedical Engineering and Experimental Mechanics, Wroclaw University of Technology, Wrocław, Poland;6. Department of Pathomorphology, Wroclaw Medical University, Wrocław, Poland;1. Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, District of Feng Tai, Street of Youanmenwai, #10 Xi TouTiao, Beijing 100069, PR China;2. Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China;1. College of Basic Medicine, Key Laboratory of Ministry of Education (Syndromes and Formulas), Key Laboratory of Beijing (Syndromes and Formulas), Beijing University of Chinese Medicine, Beijing, China;2. College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China;3. Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China;4. Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China;5. Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China;1. Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, 1113, Bulgaria;2. Institute of Polymers, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria |
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| 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. |
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