Interferon-gamma receptors are expressed at synapses in the rat superficial dorsal horn and lateral spinal nucleus

Interferon-gamma can facilitate the spinal nociceptive flexor reflex and el icit neuropathic pain-related behavior in rats and mice. Immunoreactivity f or the interferon-gamma receptor (IFN-gamma R) occurs in the superficial la yers of the dorsal horn and the lateral spinal nucleus in the rat and mouse spinal cord, as well as in subsets of neurons in the dorsal root ganglia. The aim of the present study was to examine the cellular localization and o rigin of the IFN-gamma R in the spinal cord. As viewed by confocal microsco py, the immunopositivity for the IFN-gamma R was co-localized with that of the presynaptic marker synaptophysin and with neuronal nitric oxide synthas e in the lateral spinal nucleus, whereas only a minor overlap with these mo lecules was observed in laminae I and II of the dorsal horn. There was no c o-localization of the IFN-gamma R with markers for astrocytes and microglia l cells. Ultrastructurally, the IFN-gamma R was found predominantly in axon terminals in the lateral spinal nucleus but also at postsynaptic sites in dendrites in laminae I and II. The IFN-gamma R expressed in neurons in dors al root ganglia was transported in axons both centrally and peripherally. H emisection of the spinal cord caused no reduction in immunolabelling of the IFN-gamma R in the dorsal horn or the lateral spinal nucleus. Since rhizot omy does not effect the immunolabelling in the lateral spinal nucleus, our observation indicates that the presynaptic receptors in this nucleus are de rived from intrinsic neurons. The localization of the IFN-gamma R in the sp inal cord differed from that of the AMPA glutamate receptor subunits 2 and 3 and the substance P receptor (NK1). Our results, showing localization of IFN-gamma R to pre- and postsynaptic sites in the dorsal horn and lateral s pinal nucleus indicate that IFN-gamma can modulate nociception at the spina l cord level.