Pronociceptive changes in response properties of rostroventromedial medullary neurons in a rat model of peripheral neuropathy

Abstract

The spared nerve injury (SNI) model of peripheral neuropathy produces a robust and long-lasting hypersensitivity. Previous behavioural studies suggest that brainstem–spinal pathways originating in or relaying through the rostroventromedial medulla (RVM) contribute to neuropathic hypersensitivity. We determined whether SNI induces changes in response properties of RVM neurons that might influence 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 responses to noxious stimulation, respectively). Spontaneous activity and the response to cold, pinch and colorectal distension were assessed under light anaesthesia in the rat, 1 week and 8 weeks following nerve injury or sham operation. Spontaneous activity was increased 1 week but not 8 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 8 weeks but not 1 week following nerve injury, whereas OFF-cell responses to pinch or colorectal distension were not changed. The results indicate that SNI induces pronociceptive changes in spontaneous activities of ON-cells and OFF-cells and peripherally evoked responses of ON-cells that vary with the postoperative time point. Increased ON-cell activity and decreased OFF-cell activity in the RVM are likely to enhance spinal nociception in a tonic fashion, whereas increased responses of ON-cells to peripheral stimulation are likely to enhance ascending nociceptive signals by a positive feedback following peripheral noxious stimulation.