Differential Expression of Phosphorylated ERK and c-Fos of Limbic Cortices Activities in Response to Tactile Allodynia of Neuropathic Rats

Neuropathic pain is due to lesion or dysfunction of the somatosensory system. Treating patients with neuropathic pain is difficult because the underlying mechanisms are understood limitedly, especially at the supraspinal level. In this study, we used two kinds of molecular markers to investigate the neuronal activity changes in the anterior cingulate cortex (ACC), insular cortex (IC), and medial prefrontal cortex (mPFC) of the neuropathic rats under tactile allodynia. We used spared nerve injury (SNI) of the sciatic nerve as the neuropathic pain model. Two weeks after SNI surgery, we applied repetitive allodynic stimulation to the conscious rats. After stimulation, the rats were sacrificed, and the immunohistochemistry of phosphorylated extracellular signal-regulated kinase (pERK) and c-Fos was performed. Quantification of immunoreactive cells was carried out by stereological method. For pERK study, the expression of pERK was significantly increased in the mPFC and IC of the SNI rats. For c-Fos study, only mPFC had elevated expression of c-Fos in the SNI rats. The analgesic, gabapentin, reversed the mechanical hyper-sensitivity and the augmented expression of limbic pERK and c-Fos in the SNI rats. Immunofluorescent staining revealed the expression of pERK or c-Fos was restricted to neurons, not glia cells. Our results demonstrated that tactile allodynia represented differential expression of pERK and c-Fos in the limbic cortices of the neuropathic rats.