Behavioral evidence for the differential regulation of p-p38 MAPK and p-NF-[kappa]B in rats with trigeminal neuropathic pain

Background We investigated the differential regulation of p-p38 MAPK or p-NF-[kappa]B 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-[kappa]B in the medullary dorsal horn and examined changes in nociceptive behavior after a blockade of p-p38 MAPK or p-NF-[kappa]B 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-[kappa]B in astrocyte peaked on POD 7 through 21. The intracisternal administration of SB203580 (1 or 10 [mu]g), 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-[kappa]B inhibitor, on POD 21 but not on POD 3 attenuates mechanical allodynia and p-NF-[kappa]B expression. Dexamethasone (25 mg/kg) decreases not only the activation of p38 MAPK but also that of NF-[kappa]B on POD 7. Conclusions These results suggest that early expression of p-p38 MAPK in the microglia and late induction of p-NF-[kappa]B 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-[kappa]B at a late stage might be a potential therapeutic strategy for treatment of trigeminal neuropathic pain.