title: Inhibition of p38 MAPK reduces loss of primary sensory neurons after nerve transection.
abstract: OBJECTIVE
  p38 member of mitogen-activated protein kinase (MAPK) family has been shown to participate in neuropathic pain and axonal regeneration after nerve injury. However, its role in axotomy-induced neuronal apoptosis remains unclear. This study was aimed to examine p38 phosphorylation  in the dorsal root ganglia (DRG) and its role in DRG neuronal loss after axotomy.
  
  
  METHODS
  Left sciatic nerve transection was performed in all rats. For the temporal study of p38 phosphorylation, the rats were sacrificed at 1 day, 2 weeks, and 2 months after injury. In the second  experiment, the rats were divided into control and inhibitor groups receiving vehicle and p38 inhibitor (SB203580, 200 μg/kg/day intraperitoneally once daily), respectively, for 2 weeks.
  
  
  RESULTS
  The p38 phosphorylation was increased in L4/5 DRG at 2 weeks after transection. Immunoreactivity  of phospho-p38 was mainly observed in the cytoplasm of small neurons with additional nuclear localization in the axotomized neurons at 2 weeks. SB203580 could reduce the phosphorylation of p38 and its substrate, ATF2, including the upregulation of total caspase-3 expression in the DRG. Moreover,  count of L4/5 DRG neurons revealed significantly decreased cell loss in the inhibitor than control groups (17·4% versus 32·5%).
  
  
  CONCLUSIONS
  These data suggest the role of p38 in sensory neuronal loss after nerve transection. Future studies should be done to confirm  the apoptotic role of p38 in this condition.
authors: Department of Anatomy, Faculty of Medicine, Chulalongkorn University Bangkok, Thailand. sagthong@hotmail.com
authors: Sithiporn
authors: S
authors: Agthong
authors: Atitaya
authors: A
authors: Kaewsema
authors: Vilai
authors: V
authors: Chentanez
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000201:enzymology*; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000201:enzymology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580