Gene expression profile of sodium channel subunits in the anterior cingulate cortex during experimental paclitaxel-induced neuropathic pain in mice

Paclitaxel, a chemotherapeutic agent, causes neuropathic pain whose supraspinal pathophysiology is not fully understood. Dysregulation of sodium channel expression, studied mainly in the periphery and spinal cord level, contributes to the pathogenesis of neuropathic pain. We examined gene expression of sodium channel (Na(v)) subunits by real time polymerase chain reaction (PCR) in the anterior cingulate cortex (ACC) at day 7 post first administration of paclitaxel, when mice had developed paclitaxel-induced thermal hyperalgesia. The ACC was chosen because increased activity in the ACC has been observed during neuropathic pain. In the ACC of vehicle-treated animals the threshold cycle (Ct) values for Na(v)1.4, Na(v)1.5, Na(v)1.7, Na(v)1.8 and Na(v)1.9 were above 30 and/or not detectable in some samples. Thus, comparison in mRNA expression between untreated control, vehicle-treated and paclitaxel treated animals was done for Na(v)1.1, Na(v)1.2, Na(v)1.3, Na(v)1.6, Na(x) as well as Na(v)β1–Na(v)β4. There were no differences in the transcript levels of Na(v)1.1–Na(v)1.3, Na(v)1.6, Na(x), Na(v)β1–Na(v)β3 between untreated and vehicle-treated mice, however, vehicle treatment increased Na(v)β4 expression. Paclitaxel treatment significantly increased the mRNA expression of Na(v)1.1, Na(v)1.2, Na(v)1.6 and Na(x), but not Na(v)1.3, sodium channel alpha subunits compared to vehicle-treated animals. Treatment with paclitaxel significantly increased the expression of Na(v)β1 and Na(v)β3, but not Na(v)β2 and Na(v)β4, sodium channel beta subunits compared to vehicle-treated animals. These findings suggest that during paclitaxel-induced neuropathic pain (PINP) there is differential upregulation of sodium channels in the ACC, which might contribute to the increased neuronal activity observed in the area during neuropathic pain.