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. 2013 Mar 25;123(4):1513–1530. doi: 10.1172/JCI64551

Figure 10. Hypothesized mechanisms of BA- and TGR5-induced itch and analgesia.

Figure 10

(A) Mechanisms of itch. BAs in the skin activate TGR5 on sensory nerve endings (i), which increases neuronal excitability and stimulates release of unknown transmitters from the central projections of sensory nerves in dorsal horn of the spinal cord (ii). The transmitters induce release of GRP (iii) and opioids (iv) from spinal neurons. GRP activates GRPR and opioids activate the MOR1D/GRPR heterodimer on itch-selective spinal neurons. Activated GRPR induces itch (v). (B) Mechanisms of analgesia. BAs in the skin activate TGR5 on dermal macrophages (i) to stimulate release of opioids that activate MORs and δ-opioid receptors (DOR) on sensory nerve endings to induce peripheral mechanisms of analgesia (ii). BAs in the spinal cord activate TGR5 on spinal neurons (iii) to stimulate release of opioids that activate MOR1 on pain-selective spinal neurons (iv). Activated MOR1 induces central mechanisms of analgesia (v).