{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T10:40:50Z","timestamp":1787308850993,"version":"build-2736575974"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"31","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,8,2]]},"abstract":"<jats:p>The lack of effective and safe analgesics for chronic pain management has been a health problem associated with people's livelihoods for many years. Analgesic peptides have recently shown significant therapeutic potential, as they are devoid of opioid-related adverse effects. Programmed cell death protein 1 (PD-1) is widely expressed in neurons. Activation of PD-1 by PD-L1 modulates neuronal excitability and evokes significant analgesic effects, making it a promising target for pain treatment. However, the research and development of small molecule analgesic peptides targeting PD-1 have not been reported. Here, we screened the peptide H-20 using high-throughput screening. The in\u00a0vitro data demonstrated that H-20 binds to PD-1 with micromolar affinity, evokes Src homology 2 domain\u2013containing tyrosine phosphatase 1 (SHP-1) phosphorylation, and diminishes nociceptive signals in dorsal root ganglion (DRG) neurons. Preemptive treatment with H-20 effectively attenuates perceived pain in na\u00efve WT mice. Spinal H-20 administration displayed effective and longer-lasting analgesia in multiple preclinical pain models with a reduction in or absence of tolerance, abuse liability, constipation, itch, and motor coordination impairment. In summary, our findings reveal that H-20 is a promising candidate drug that ameliorates chronic pain in the clinic.<\/jats:p>","DOI":"10.1073\/pnas.2204114119","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T15:21:05Z","timestamp":1658762465000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":28,"title":["An analgesic peptide H-20 attenuates chronic pain via the PD-1 pathway with few adverse effects"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1843-753X","authenticated-orcid":false,"given":"Long","family":"Zhao","sequence":"first","affiliation":[{"name":"Center for Basic Medical Research, Medical School of Nantong University, Nantong 226001, Jiangsu Province, 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