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. Author manuscript; available in PMC: 2024 Aug 1.
Published in final edited form as: Pharmacol Ther. 2023 Jun 10;248:108476. doi: 10.1016/j.pharmthera.2023.108476

Figure 1. Immunotherapy targeting the PD-L1/PD-1 pathway in chronic pain through neuronal and immune modulation.

Figure 1.

(A) Neuronal modulation: Activation of PD-1 in DRG sensory neurons by PD-L1 causes phosphorylation of SHP-1, leading to the activation of mu opioid receptor (MOR) and potassium channel TREK2 and inactivation of sodium channels (e.g. Nav1.7) and TRPV1. SHP-1 activation also inhibits ERK phosphorylation. Through the PD-1/SHP1-mediated signaling, PD-L1 potently inhibits physiological and pathological pain. (B) Immune modulation: In bone cancer pain, activation of PD-1 by PD-L1 on osteoclasts can promote osteoclastogenesis in cancer-bearing bone marrow, leading to CCL2 secretion and CCR2 activation on osteoclasts and nociceptors. Anti-PD-1 treatment with nivolumab inhibits bone cancer pain through suppression of osteoclastogenesis and bone destruction and reduced CCR2 signaling in nociceptors.