Antinociceptive action of a p38alpha MAPK inhibitor, SD-282, in a diabetic neuropathy model
| Autor: | Sarvajit Chakravarty, Ramona Almirez, David C. Yeomans, Sundeep Dugar, Sarah M. Sweitzer, Satyanarayana Medicherla, Andrew A. Protter, Jennifer A. Shumilla |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Diabetic neuropathy Analgesic Pharmacology Nerve Fibers Myelinated p38 Mitogen-Activated Protein Kinases Drug Administration Schedule Diabetes Mellitus Experimental Rats Sprague-Dawley Diabetic Neuropathies Diabetes mellitus medicine Animals Peripheral Nerves Enzyme Inhibitors Pain Measurement Analgesics Nerve Fibers Unmyelinated Dose-Response Relationship Drug business.industry Nociceptors medicine.disease Streptozotocin Rats Disease Models Animal Anesthesiology and Pain Medicine Allodynia Nociception Neurology Hyperalgesia Anesthesia Nociceptor Neuralgia Neurology (clinical) medicine.symptom Mitogen-Activated Protein Kinases business medicine.drug |
| Zdroj: | PainReferences. 109(3) |
| ISSN: | 0304-3959 |
| Popis: | Diabetes can induce a bewildering list of sensory changes, including alteration in pain sensitivity. Painful diabetic neuropathy is refractory to most common analgesics. This study examined the effect of a p38alpha MAPK inhibitor, SD-282, on mechanical allodynia, thermal hyperalgesia, and formalin-evoked nociception in streptozotocin-induced diabetic rats. Four-week diabetic rats exhibited mechanical allodynia, decreased mechanical thresholds, and C- and Adelta-fiber mediated thermal hyperalgesia. Mechanical and thermal responses were measured in diabetic rats following acute and repeated intraperitoneal administration of vehicle, 15 or 45 mg/kg SD-282. Mechanical allodynia was reversed by acute and repeated administration of 15 and 45 mg/kg SD-282. Repeated administration of 15 or 45 mg/kg SD-282 prevented the exacerbation of C-, but not Adelta-fiber, mediated thermal hyperalgesia. Repeated administration of 45 mg/kg SD-282 attenuated flinching behaviors during the quiescent period and the second phase of the formalin response in diabetic rats. Acute and repeated administration of 15 or 45 mg/kg SD-282 had no effect on mechanical, thermal or formalin responses in age-matched control rats. These results indicate a potential therapeutic value of p38alpha MAPK inhibitors in the treatment of aberrant pain sensitivity produced by diabetes. |
| Databáze: | OpenAIRE |
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