Biological Roles of Resolvins and Related Substances in the Resolution of Pain

Figure 3

Signaling mechanisms of resolvin actions on the pain-mediating DRG neurons and their synapses. (a) RvE1 suppresses TRPV1 activity, and RvD1 suppresses TRPA1, TRPV3, and TRPV4 activities in DRG nerve terminals. (b) RvE1 attenuates TNF-α signaling and ERK activation in DRG neuronal cell bodies. In the same regions, AT-RvD1 downregulates COX-2 and NF-κB expressions. (c) RvE1 reduces excitatory neurotransmitter releases and TNF-α signaling at the central presynaptic terminals. (d) RvE1 suppresses overactivated ERK and NMDA receptor at postsynaptic dorsal horn neurons in the spinal cord. DRG, dorsal root ganglion; GLU, glutamate; NMDAR, NMDA receptor; TNFR, TNF-α receptor; TRPA1, transient receptor potential ankyrin subtype 1; TRPV1, transient receptor potential vanilloid subtype 1; TRPV3, transient receptor potential vanilloid subtype 3; TRPV4, transient receptor potential vanilloid subtype 4.