{
  "abstract": "Chronic pain constitutes a major global health burden, and current management remains largely dependent on opioid analgesics, which are associated with opioid use disorder. Accordingly, there is a pressing need to identify non-opioid therapeutic strategies. Galanin receptors (GALR1–3) have been implicated in pain modulation, but their individual roles remain insufficiently defined because of the absence of subtype-selective ligands. Recently, spexin has been identified as an endogenous peptide that selectively activates GALR2 and GALR3, offering a new scaffold for developing pharmacological tools targeting these receptor subtypes. In this study, we designed and characterized LIT-01-144, a modified spexin analog incorporating N-terminal fluorocarbon functionalization to improve metabolic stability while preserving receptor selectivity. In vitro pharmacological profiling demonstrated high potency at GALR2 and GALR3, with negligible activity at GALR1. Pharmacokinetic analyses showed a substantially prolonged plasma half-life relative to native spexin and no evidence of central nervous system penetration. In vivo, intracerebroventricular administration of LIT-01-144 produced robust antinociception at doses tenfold lower than those required for spexin. Although systemic administration had no detectable effect in naïve mice, it significantly attenuated pain-related behaviors in a model of persistent inflammatory pain. This effect was mediated specifically by GALR2 and was independent of opioid receptor signaling. In situ hybridization further showed an increase in Galr2 + neurons in dorsal root ganglia of inflamed mice. Collectively, these findings highlight GALR2 as a promising peripheral target for developing non-opioid analgesics and demonstrate the potential of LIT-01-144 as a valuable tool for understanding GALR2-mediated mechanisms of pain modulation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "Yann Berthomé"
    },
    {
      "name": "Glenn-Marie Le Coz"
    },
    {
      "name": "Valérie Utard"
    },
    {
      "name": "Qiuxiang Gu"
    },
    {
      "name": "Rosine Fellmann-Clauss"
    },
    {
      "name": "Nathalie Petit-Demoulière"
    },
    {
      "name": "Raphaëlle Quillet"
    },
    {
      "name": "Claire Gavériaux-Ruff"
    },
    {
      "name": "Sridevi M. Ramanoudjame"
    },
    {
      "name": "Lucie Estéoulle"
    },
    {
      "name": "Nicolas Humbert"
    },
    {
      "name": "François Daubeuf"
    },
    {
      "name": "Patrick Gizzi"
    },
    {
      "name": "Stéphanie Riché"
    },
    {
      "name": "Xavier Leroy"
    },
    {
      "name": "Dominique Bonnet"
    },
    {
      "name": "Frédéric Simonin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/28fncfp0e2d97.bib",
  "cited_by": 0,
  "doi": "10.1016/j.biopha.2026.119987",
  "fulltext_url": null,
  "id": "28fncfp0e2d97",
  "issns": [
    "0753-3322",
    "1950-6007"
  ],
  "landing_url": "https://hal.science/hal-05845252v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.chim"
    ],
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2737|Pain Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7222829742",
  "pdf_url": "https://hal.science/hal-05845252/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-17",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/28fncfp0e2d97.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:03Z",
      "native_id": "hal-05845252",
      "source": "hal",
      "url": "https://hal.science/hal-05845252v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Pain Mechanisms and Treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Peripheral GALR2 activation by the metabolically stabilized spexin analog LIT-01-144 produces potent opioid‑independent antinociception",
  "title_text": "Peripheral GALR2 activation by the metabolically stabilized spexin analog LIT-01-144 produces potent opioid‑independent antinociception",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:20:45Z",
  "url": "https://research.draconitic.com/paper/28fncfp0e2d97",
  "venue": "Biomedicine and Pharmacotherapy",
  "versions": []
}