FIGURE 2.

Schematic illustration of pain sensitization and the possible involvement of MOPr-DOPr heteromers and RTP4 in the regulation of pain sensation (Hypothesis). The peripheral nerve injury will stimulate peripheral immune response cells like macrophages that can produce type I IFN. RTP4 could be upregulated following the IFNARs/TNFRs activation in DRG neurons and thus induce the upregulation of MOPr-DOPr heteromer at the cell surface membrane (as a part of compensatory mechanisms occurring during neuropathic pain). Although the critical role for RTP4 and the MOPr-DOPr heteromer in pain sensitization at the spinal cord and the central nervous system is still not clear, the MOPr-DOPr heteromer and RTP4 could be a potent therapeutic target for pain treatment.