In this study we investigate temporal changes in Fos expression in cuneate neurons after a high-threshold electrical stimulation of the transected median nerve in rats. Two hours after injury of the median nerve when given electrical stimulation, c-Fos-immunoreactive (c-Fos-IR) cells were barely detected in the ipsilateral cuneate nucleus (CN). A few c-Fos-IR cells, however, were observed in the ipsilateral CN at 5 days. A marked increase in c-Fos-IR cells was observed at 2, 3, and 4 weeks, but levels subsided thereafter. Labeled cells were totally diminished by 16 weeks. The statistical analysis showed that the mean density of c-Fos-IR cells throughout the CN at 4 weeks was significantly higher than at other post-surgical time points, except for 3 weeks. Furthermore, the mean density of c-Fos-IR cells in the middle region of the CN was markedly higher than in other areas of the nucleus. The mean density of c-Fos-IR cells in the middle region at 4 weeks (mean density = 35.9 +/- 3.0 cells/section) was considerably higher than at other time points. Combined retrograde Fluorogold (FG) labeling and c-Fos immunocytochemistry showed that throughout the CN about 60% (2270/3652) of the c-Fos-IR cells contained FG, confirming that they were cuneothalamic projection neurons (CTNs). Moreover, the percentage of double-labeled cells in the middle region at 2 weeks (78.9 +/- 0.6%) was significantly greater than at 3 (70.2 +/- 3.4%) and 4 weeks (66.0b +/- 1.4%) after injury. Although the mechanism leading to the vigorous c-Fos expression in the CTNs following the electrical stimulation of the transected median nerve remains unclear the hyperexcitable CTNs may transmit the neuropathic nociceptive sensation to the thalamus after the median nerve injury.