Objective: It has been shown that interferon-α (IFN-α) is synthesized and secreted by macrophages, monocytes, T lymphocytes, glial cells and neurons. IFN-α has been shown to have an antinociceptive effect at the supraspinal level in the nerve system. However, it is unclear how IFN-α is involved in the modulation of nociceptive transmission in the spinal cord. Methods: In the present study, IFN-α was used to test the potential functional roles in the nociceptive transmission. Using the whole-cell patch-clamp technique, we examined the effects of IFN-α on substantia gelatinosa (SG) neurons in the dorsal root-attached spinal cord slice prepared from adult rats. Results: We found that IFN-α increased glutamatergic excitatory postsynaptic currents evoked by the stimulation of either Aδ or C afferent fibers. Further studies showed that IFN-α treatment dose-dependently increased spontaneous excitatory postsynaptic current frequency in SG neurons, while not affecting the amplitude. Moreover, intrathecal antibody of IFN-α could reduce nociceptive responses in formalin test. Conclusions: These results suggest that IFN-α presynaptically facilitates the excitatory synaptic transmission to SG neurons. The nociceptive responses could be inhibited by IFN-α antibody in the formalin test. Thus, IFN-α enhances the nociceptive transmission, which contributes to the behavioral nociceptive responses.

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