ArticleProceedings of the National Academy of Sciences of the United States of America2022
An analgesic peptide H-20 attenuates chronic pain via the PD-1 pathway with few adverse effects.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.Cellular and molecular neurobiology · 2023Pooled it
- Protocol for a cohort study: evaluating the effect of neoadjuvant immunochemotherapy on intraoperative remifentanil consumption during IoC2-guided anesthesia in elderly patients with esophageal cancer.Annals of medicine · 2026Observational
- Applications of micro/nano drug delivery systems in cancer pain management.Bioactive materials · 2026Review
- Programmed Cell Death Ligand 1 Is Essential for Electroacupuncture-Mediated Analgesia in the Cerebellum of Fibromyalgia Mice.Biomedicines · 2026Article
- CD28 Superfamily Costimulatory Molecules in Chronic Pain: Focus on Immunomodulation.Molecular neurobiology · 2025Review
- Effect of microglial Pd1 on glial scar formation after spinal cord injury in mice.The Journal of biological chemistry · 2025Article
- Electroacupuncture Modulates Programmed Cell Death 1 Ligand 1 on Peripheral and Central Nervous Systems in a Mouse Fibromyalgia Pain Model.Biomedicines · 2025Article
- Establishment of a Magnetically Controlled Scalable Nerve Injury Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cancer Therapy-induced Dermatotoxicity as a Window to Understanding Skin Immunity.Hematology/oncology clinics of North America · 2024Review
- Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region.Scientific reports · 2024Article
- PD-L1/PD-1 pathway: a potential neuroimmune target for pain relief.Cell & bioscience · 2024Review
- Antiaging Strategies and Remedies: A Landscape of Research Progress and Promise.ACS chemical neuroscience · 2024Review
- Immunotherapies in chronic pain through modulation of neuroimmune interactions.Pharmacology & therapeutics · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 vitro data demonstrated that H-20 binds to PD-1 with micromolar affinity, evokes Src homology 2 domain-containing 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 naïve 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.