It is well known that interferons (IFNs), such as type-I IFN (IFN-α) and type-II IFN (IFN-γ) are produced by immune cells to elicit antiviral effects. IFNs are also produced by glial cells in the CNS to regulate brain functions. As a proinflammatory cytokine, IFN-γ drives neuropathic pain by inducing microglial activation in the spinal cord. However, little is known about the role of IFN-α in regulating pain sensitivity and synaptic transmission. Strikingly, we found that IFN-α/β receptor (type-I IFN receptor) was expressed by primary afferent terminals in the superficial dorsal horn that co-expressed the neuropeptide CGRP. In the spinal cord IFN-α was primarily expressed by astrocytes. Perfusion of spinal cord slices with IFN-α suppressed excitatory synaptic transmission by reducing the frequency of spontaneous excitatory postsynaptic current (sEPSCs). IFN-α also inhibited nociceptive transmission by reducing capsaicin-induced internalization of NK-1 and phosphorylation of extracellular signal-regulated kinase (ERK) in superficial dorsal horn neurons. Finally, spinal (intrathecal) administration of IFN-α reduced inflammatory pain and increased pain threshold in naïve rats, whereas removal of endogenous IFN-α by a neutralizing antibody induced hyperalgesia. Our findings suggest a new form of neuronal-glial interaction by which IFN-α, produced by astrocytes, inhibits nociceptive transmission in the spinal cord.

MicroRNAs (miRNAs) are small noncoding RNA molecules of 18-25 nucleotides in length that regulate gene expression involved in fundamental cell processes. The induction and chronification of pain is associated with many expressional changes in pain-related proteins. miRNA has the potential to regulate gene and protein expression associated with the induction and chronification of pain. Thus, miRNAs might have promise in therapy and as a diagnostic and prognostic biomarker in pain medicine. The application of miRNA has been an emerging field in pain research in recent years. Many studies focusing on the regulation of miRNAs under different tissue and nociceptive stimuli have been performed in recent years. In this review, we intend to introduce the most recent research in the field of miRNA related with pain medicine such as the expression and function of miRNA in different animal pain model, the challenge of application and delivery of miRNA in vivo, the potential toxic effects of miRNA and future problems in clinical application that need to be resolved. This review focuses on the results of miRNA in animal studies and the prospect for future success.

There is accumulating evidence to implicate the importance of N-methyl-d-aspartate (NMDA) receptors to the induction and maintenance of central sensitization during pain states. However, the use of NMDA receptor antagonists can often be limited by serious central nervous system side effects. The development of peripheral NMDA receptor antagonists that do not interfere with central glutamate processing can avoid adverse effects of the central nervous system. RNA interference is an evolutionarily conserved mechanism for silencing gene expression in which a targeted mRNA is degraded by a double-stranded RNA sequence known as a small interfering RNA (siRNA). siRNAs can be derived from short hairpin (sh) RNAs, which can be expressed from plasmids or viral vectors to achieve long-term gene silencing. In this study, we examined the effect of gene silence and antinociception on formalin-induced pain by subcutaneous injection of vector-encoding shRNA targeting the NR1 subunit of the NMDA receptor. The results revealed that subcutaneous injection of vector-expressing NR1 shRNA could effectively diminish the nociception induced by formalin stimuli and inhibit gene expression of NR1 evidenced by a decreased level of mRNA and protein. The effect of antinociception and inhibition of NR1 expression by NR1 shRNA persisted for about 14days. The data suggest that NR1 shRNA has therapeutic potential to provide long-term treatment of pathological pain that is induced or maintained by peripheral nociceptor activity. Subcutaneous injection of NR1 short hairpin RNA has the therapeutic potential of providing long-term treatment of pathological pain that is induced or maintained by peripheral nociceptor activity.