{
  "abstract": "IntroductionInflammatory pain is a key component of both acute and chronic pain conditions that, when pathological, significantly decrease patient quality of life. There has been a recent interest in the use of cannabinoid-based compounds for analgesia and recent research has discovered functional connections between the CB2 and 5-HT1A receptors.MethodsTherefore, we investigated the efficacy of CB1-selective agonism (ACEA) and CB2-selective agonism (AM1241), and their potential reliance on the 5-HT1A receptor, in the formalin inflammatory pain model using female and male adult C57BL/6J mice. Potential dose- and sex-differences were assessed for ACEA (at 0.1-2.5 mg/kg) and AM1241 (at 1-10 mg/kg) in the formalin test. Subsequent experiments were conducted using either ACEA (0.5 mg/kg) or AM1241 (10 mg/kg), alone or with inhibition of 5-HT1A via WAY-100635, in both the formalin model of inflammatory pain and the non-nociceptive components of the cannabinoid tetrad test (open field, rotarod, rectal temperature).ResultsACEA provided significant pain relief at 0.5 mg/kg in female mice and at 0.5 and 0.75 mg/kg in male mice, with significant sex differences observed. ACEA (0.5 mg/kg) antinociception was unaltered by 5-HT1A inhibition while AM1241 (10 mg/kg) antinociception was completely prevented in the acute phase by 5-HT1A inhibition. Neither ACEA nor AM1241 significantly altered performance in the open field, rotarod, or rectal temperature assessments.DiscussionThese results demonstrate the antinociceptive benefit of CB1 and CB2 agonism in a murine model of inflammatory pain while demonstrating further evidence of a functional link between the CB2 and 5-HT1A receptors. Further studies are needed to investigate the mechanism behind this connection and its potential clinical significance.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United States",
    "Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX, United States",
    "Brain Drug Discovery Center, Texas Tech University Health Sciences Center, Amarillo, TX, United States"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Robert C. Barnes"
    },
    {
      "affs": [
        0
      ],
      "name": "Hannah Quick"
    },
    {
      "affs": [
        0
      ],
      "name": "Dakota Robison"
    },
    {
      "affs": [
        0
      ],
      "name": "Aric F. Logsdon"
    },
    {
      "affs": [
        1
      ],
      "name": "Aric F. Logsdon"
    },
    {
      "affs": [
        2
      ],
      "name": "Aric F. Logsdon"
    },
    {
      "affs": [
        0
      ],
      "name": "Josée Guindon"
    },
    {
      "affs": [
        1
      ],
      "name": "Josée Guindon"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8p7z0g8n6t9p5.bib",
  "cited_by": 0,
  "doi": "10.3389/fpain.2026.2005000",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fpain.2026.2005000/full",
  "id": "8p7z0g8n6t9p5",
  "issns": [
    "2673-561X"
  ],
  "landing_url": "https://doi.org/10.3389/fpain.2026.2005000",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC346-429"
    ],
    [
      "openalex",
      "2736|Cannabis and Cannabinoid Research"
    ]
  ],
  "openalex": "W7223704751",
  "pdf_url": "https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2026.2005000/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Frontiers Media S.A.",
  "ris": "https://research.draconitic.com/paper/8p7z0g8n6t9p5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:47:33Z",
      "native_id": "c47efe095b8d4bd3880363970ea4ba1c",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fpain.2026.2005000"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Cannabis and Cannabinoid Research",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Assessing CB1 and CB2 receptor agonist antinociception while exploring sex differences and 5-HT1A-dependent mechanisms",
  "title_text": "Assessing CB1 and CB2 receptor agonist antinociception while exploring sex differences and 5-HT1A-dependent mechanisms",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:47:33Z",
  "url": "https://research.draconitic.com/paper/8p7z0g8n6t9p5",
  "venue": "Frontiers in Pain Research",
  "versions": []
}