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. Author manuscript; available in PMC: 2024 Dec 1.
Published in final edited form as: Trends Pharmacol Sci. 2023 Nov 11;44(12):1009–1027. doi: 10.1016/j.tips.2023.10.003

Figure 2. Innovative strategies to target GPCRs on primary sensory neurons for achieving site-specific analgesia.

Figure 2.

Approaches aimed at targeting GPCRs on the peripheral terminals and the cell body of primary sensory neurons (PSNs) to develop analgesics with increased safety and efficacy are depicted. These include development of peripheral restricted compounds, prodrugs, targeting GPCR heteromers, and co-activation of dual GPCR receptors. Other strategies such as NDDS (novel drug delivery systems), cell specific discovery, and compartmentalized signaling are also shown. In addition, the approach of enhancing the activity of endogenous agonists at the central terminals of PSNs by positive allosteric modulators (PAMs), such as MrgX1 PAMs, is also shown.