Recent studies have demonstrated an important role of the pro-inflammatory cytokine interferon-γ in neuropathic pain. Interferon-γ is upregulated in the lumbar spinal cord of nerve-injured rodents and intrathecal injection of interferon-γ 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-γ 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-γ on spontaneous excitatory postsynaptic currents or on monosynaptic Aδ- and C-fibre-evoked excitatory postsynaptic currents, respectively. Prolonged treatment with interferon-γ 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, Aδ-fibre-evoked excitatory postsynaptic currents were not affected by the prolonged interferon-γ treatment. Acute interferon-γ application in the bathing solution did not change strength of monosynaptic Aδ- 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-γ 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-γ modifies the processing of information at the first synaptic relay station in nociceptive pathways.
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| http://dx.doi.org/10.1177/1744806920917249 | DOI Listing |
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