Interferon-gamma facilitates the synaptic transmission between primary afferent C-fibres and lamina I neurons in the rat spinal dorsal horn via microglia activation

Recent studies have demonstrated an important role of the pro-inflammatory cytokine interferon-gamma in neuropathic pain. Interferon-gamma is upregulated in the lumbar spinal cord of nerve-injured rodents and intrathecal injection of interferon-gamma has been shown to induce neuropathic pain-like behaviours in naive rodents. A potential mechanism in the pathogenesis of neuropathic pain is a long-lasting amplification of nociceptive synaptic transmission in lamina I of the spinal dorsal horn. Here, we tested the effects of interferon-gamma on the properties of the first synapse in nociceptive pathways in the superficial spinal dorsal horn. We performed whole-cell patch-clamp recordings in lamina I neurons in a spinal cord slice preparation with dorsal roots attached from young rats. We determined the effects of acute (at least 25 min) or longer lasting (4-8 h) treatment of the transversal slices with recombinant rat interferon-gamma on spontaneous excitatory postsynaptic currents or on monosynaptic A delta- and C-fibre-evoked excitatory postsynaptic currents, respectively. Prolonged treatment with interferon-gamma facilitated monosynaptic C-fibre-evoked excitatory postsynaptic currents and this effect could be blocked by co-application of minocycline an inhibitor of microglial activation. In contrast, A delta-fibre-evoked excitatory postsynaptic currents were not affected by the prolonged interferon-gamma treatment. Acute interferon-gamma application in the bathing solution did not change strength of monosynaptic A delta- or C-fibre synapses in lamina I. However, the rate, but not the amplitude, of spontaneous excitatory postsynaptic currents recorded in lamina I neurons was decreased. This effect could not be blocked by the application of minocycline. Long-lasting treatment of rat spinal cord slices with interferon-gamma induced an input specific facilitation of synaptic strength in spinal nociceptive pathways. Enhanced transmission between C-fibres and spinal lamina I neurons was mediated by the activation of microglial cells. We showed that the pro-inflammatory cytokine interferon-gamma modifies the processing of information at the first synaptic relay station in nociceptive pathways.