Spared nerve injury (SNI) model of peripheral neuropathy produces a robust and long-lasting hypersensitivity. We determined with microelectrode recordings in the pentobarbitone- anesthetized rat the effect of SNI on response properties of neurons in the rostroventromedial medulla (RVM), a relay for descending modulation of nociception. RVM neurons included in the study were classified into presumably pronociceptive ON- cells and antinociceptive OFF-cells (giving excitatory or inhibitory response to noxious stimulation, respectively). Spontaneous activity and the response to noxious cold, pinch, colorectal distension and glutamatergic manipulation of the amygdala were assessed one and eight weeks following nerve injury or sham operation. Spontaneous activity was increased one but not eight weeks after nerve injury in ON- cells but decreased in OFF-cells at both time points. In the SNI group, cold-evoked responses were enhanced particularly in ON-cells, independent of the postoperative time point. Responses of ON-cells to pinch and visceral stimulation were enhanced eight but not one week following nerve injury, while OFF-cell responses to pinch or colorectal distension were not changed. Glutamate or an NMDA receptor antagonist in the amygdala produced only minor changes in the discharge rate of RVM neurons. The results indicate that SNI induces pronociceptive changes in spontaneous activities of ON- and OFF-cells and peripherally evoked responses of ON-cells that vary with the postoperative time point. These plastic changes in response properties of RVM cells may promote pain-related responses not only in a tonic fashion but also by a positive feedback loop following peripheral noxious stimulation