Peripheral nerve injury alters the expression of NF-κB in the rat's hippocampus

The hippocampus plays an important role in learning and memory and possibly contributes to the formation of pain-related memory and emotional responses. However, there is currently little data linking the hippocampus to neuropathic pain. It has been reported that NF-κB is an important regulatory factor in memory consolidation within the hippocampus. This study aims to examine a possible relationship between the hippocampal NF-κB expression and nerve injury-induced thermal hyperalgesia using a rat model of constriction sciatic nerve injury (CCI). Immunofluorescence and Western blot analysis were performed to detect and quantify the hippocampal NF-κB expression. Thermal hyperalgesia was examined on day 0 and postoperative days 1, 7 and 14. The nuclear portion of the p65 NF-κB expression was significantly increased on the contralateral side on days 7 and 14 as well as significantly increased on the ipsilateral side on day 14 as compared to the sham control group. Intraperitoneal administration of MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, reduced hyperalgesia and modulated the NF-κB expression in the contralateral side of hippocampus. These results suggest an association between the hippocampal NF-κB expression and the behavioral manifestation of thermal hyperalgesia, which is likely to be mediated through activation of the NMDA receptor.

Research Highlights► Hippocampus plays an important role in learning and memory. ► After nerve injury, NF-κB is increased in the contralateral hippocampus on days 7 and 14. ► NF-κB is increased in the ipsilateral hippocampus on day 14 post-nerve injury. ► Changes in NF-κB expression are reversed with NMDA receptor antagonism. ► Hippocampal NF-κB may contribute to pain-related memories in neuropathic pain.