Antinociceptive action of a p38alpha MAPK inhibitor, SD-282, in a diabetic neuropathy model.

Abstract

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.

• Authors: Sarah M Sweitzer, Satyanarayana Medicherla, Ramona Almirez, Sundeep Dugar, Sarvajit Chakravarty, Jennifer A Shumilla, David C Yeomans, Andrew A Protter
• Journal: Pain (Pain) Vol. 109 Issue 3 Pg. 409-419 (Jun 2004) ISSN: 0304-3959 [Print] United States
• PMID: 15157702 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Analgesics
• Enzyme Inhibitors
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Analgesics (pharmacokinetics, therapeutic use)
• Animals
• Diabetes Mellitus, Experimental (complications)
• Diabetic Neuropathies (drug therapy, enzymology, physiopathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Enzyme Inhibitors (pharmacokinetics, therapeutic use)
• Hyperalgesia (drug therapy, enzymology, physiopathology)
• Male
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Nerve Fibers, Myelinated (drug effects, enzymology)
• Nerve Fibers, Unmyelinated (drug effects, enzymology)
• Neuralgia (drug therapy, enzymology, physiopathology)
• Nociceptors (drug effects, physiology)
• Pain Measurement (drug effects)
• Peripheral Nerves (drug effects, enzymology, physiopathology)
• Rats
• Rats, Sprague-Dawley
• p38 Mitogen-Activated Protein Kinases