Inhibition of p38 MAPK reduces loss of primary sensory neurons after nerve transection

• Published in: Neurological research (New York) 2012-09, Vol.34 (7), p.714-720
• Main Authors: Agthong, Sithiporn, Kaewsema, Atitaya, Chentanez, Vilai
• Format: Article
• Language: English
• Subjects: Animals; Ganglia, Spinal - drug effects; Ganglia, Spinal - enzymology; Imidazoles - pharmacology; Imidazoles - therapeutic use; MAPK; Nerve injury; Neuronal loss; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - physiology; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Pyridines - pharmacology; Pyridines - therapeutic use; Rats; Sciatic Neuropathy - drug therapy; Sciatic Neuropathy - enzymology; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - enzymology; Transection
• ISSN: 0161-6412; 1743-1328
• DOI: 10.1179/1743132812Y.0000000070

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%). Conclusion: 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.