PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.

Journal Article (Journal Article)

Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evoked analgesia in naive mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induced mechanical allodynia. Mice lacking Pd1 (Pdcd1) exhibited thermal and mechanical hypersensitivity. PD-1 activation in DRG nociceptive neurons by PD-L1 induced phosphorylation of the tyrosine phosphatase SHP-1, inhibited sodium channels and caused hyperpolarization through activation of TREK2 K+ channels. PD-L1 also potently suppressed nociceptive neuron excitability in human DRGs. Notably, blocking PD-L1 or PD-1 elicited spontaneous pain and allodynia in melanoma-bearing mice. Our findings identify a previously unrecognized role of PD-L1 as an endogenous pain inhibitor and a neuromodulator.

Full Text

Duke Authors

Cited Authors

  • Chen, G; Kim, YH; Li, H; Luo, H; Liu, D-L; Zhang, Z-J; Lay, M; Chang, W; Zhang, Y-Q; Ji, R-R

Published Date

  • July 2017

Published In

Volume / Issue

  • 20 / 7

Start / End Page

  • 917 - 926

PubMed ID

  • 28530662

Pubmed Central ID

  • PMC5831162

Electronic International Standard Serial Number (EISSN)

  • 1546-1726

Digital Object Identifier (DOI)

  • 10.1038/nn.4571


  • eng

Conference Location

  • United States