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

Pain. 2004 Jun;109(3):409-419. doi: 10.1016/j.pain.2004.02.016.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


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