Differential expression of p65 NF-κB in the rat's brain regions induced by chronic constriction nerve injury

Abstract

Subjective pain experience has both sensory-discriminative and motivational-affective dimensions, which may be processed at different spinal cord and brain regions such as the thalamus, somatosensory cortex and the limbic system. Human brain imaging studies have suggested that some brain areas outside the traditional pain pathway contribute to the affective aspect of pain. However, the role of various brain regions in the initiation and maintenance of neuropathic pain is still unclear. It has been reported that NF-κB, a transcription factor family that involves in inflammation, cell survival and synaptic signaling, might play an important role in neuropathic pain condition. To date, little is known about its expression under neuropathic pain condition beyond the spinal cord. Here we examined the extended expression of p65, a subunit of the NF-κB family, in both the spinal cord and brain regions in a rat model of chronic constriction sciatic nerve injury (CCI). Behavioral tests, immunohistochemistry and western blot analysis were performed. After CCI, rats showed thermal hyperalgesia and mechanical allodynia on postoperative day 1, which lasted for at least 14 days. In the lumbar spinal cord, the nuclear portion of the p65 expression was significantly increased on the ipsilateral side on postoperative day 14 as compared to a sham control group. In contrast, the p65 expression in the contralateral somatosensory cortex decreased significantly on postoperative days 1 and 7 but then returned to the baseline level on day 14. In the contralateral amygdala, the p65 expression showed a time-dependent downregulation after CCI, which was significantly different on postoperative day 14 from that of the control group. Of interest is that no significant differences in the p65 expression were detected in the thalamus on postoperative days 1, 7 or 14 as compared to the sham group. These results indicated that the expression of p65 NF-κB was both time-dependent after CCI and region-specific across the spinal cord and brain region involved in both sensory-discriminative and motivational-affective dimensions of pain processing.