Behavioral Evidence for the Differential Regulation of p-p38 MAPK and p-NF-κB in Rats with Trigeminal Neuropathic Pain

• Published in: Molecular pain 2011-08, Vol.7 (1), p.57-57
• Main Authors: Lee, Min K, Han, Seung R, Park, Min K, Kim, Min J, Bae, Yong C, Kim, Sung K, Park, Jae S, Ahn, Dong K
• Format: Article
• Language: English
• Subjects: Alveoli; Analgesics - pharmacology; Anesthesia; Animals; Behavior, Animal - drug effects; Dental prosthetics; Dexamethasone; Dexamethasone - pharmacology; Dorsal horn; Fluorescent Antibody Technique; Imidazoles - pharmacology; Immunofluorescence; Male; MAP kinase; Microglia; Neuralgia; Neuralgia - enzymology; Neuralgia - pathology; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB protein; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Pain; Pain perception; Peptides - pharmacology; Phosphorylation - drug effects; Protein Transport - drug effects; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Rodents; Time Factors; Transplants & implants; Trigeminal Nerve - drug effects; Trigeminal Nerve - enzymology; Trigeminal Nerve - pathology
• ISSN: 1744-8069; 1744-8069
• DOI: 10.1186/1744-8069-7-57

Background: We investigated the differential regulation of p-p38 MAPK or p-NF-κB in male Sprague-Dawley rats with inferior alveolar nerve injury resulting from mal-positioned dental implants. For this purpose, we characterized the temporal expression of p-p38 MAPK or p-NF-κB in the medullary dorsal horn and examined changes in nociceptive behavior after a blockade of p-p38 MAPK or p-NF-κB pathways in rats with trigeminal neuropathic pain. Results: Under anesthesia, the left lower second molar was extracted and replaced with a mini dental implant to intentionally injure the inferior alveolar nerve. Western and immunofluorescence analysis revealed that p-p38 MAPK is upregulated in microglia following nerve injury and that this expression peaked on postoperative day (POD) 3 through 7. However, the activation of p-NF-κB in astrocyte peaked on POD 7 through 21. The intracisternal administration of SB203580 (1 or 10 μg), a p38 MAPK inhibitor, on POD 3 but not on POD 21 markedly inhibits mechanical allodynia and the p-p38 MAPK expression. However, the intracisternal administration of SN50 (0.2 or 2 ng), an NF-κB inhibitor, on POD 21 but not on POD 3 attenuates mechanical allodynia and p-NF-κB expression. Dexamethasone (25 mg/kg) decreases not only the activation of p38 MAPK but also that of NF-κB on POD 7. Conclusions: These results suggest that early expression of p-p38 MAPK in the microglia and late induction of p-NF-κB in astrocyte play an important role in trigeminal neuropathic pain and that a blockade of p-p38 MAPK at an early stage and p-NF-κB at a late stage might be a potential therapeutic strategy for treatment of trigeminal neuropathic pain.