ArticleMolecular pain2011
5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, is responsible for complete Freund's adjuvant-induced thermal hyperalgesia in mice.
Article in Molecular pain, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 32 citations in OpenAlex.
- Leptomeningeal metastatic cancer cells induce a permissive choroid plexus vasculature through extracellular-vesicle-derived 5-HIAA signaling.Nature cancer · 2026Article
- Urinary 5-HIAA as a Potential Diagnostic Marker in Acute Appendicitis: A Preliminary Report of Its Promising Role in Early Detection.Medicina (Kaunas, Lithuania) · 2025Article
- Plasma serotonin precursors and metabolites as diagnostic and therapeutic biomarkers for osteoporosis in postmenopausal women.Biomolecules & biomedicine · 2025Article
- The Role of the Insular Cortex and Serotonergic System in the Modulation of Long-Lasting Nociception.Cells · 2024Article
- Serotonin Transporter (5-Hydroxytryptamine Transporter, SERT, SLC6A4) and Sodium-dependent Reuptake Inhibitors as Modulators of Pain Behaviors and Analgesic Responses.The journal of pain · 2024Review
- Exploring the Mechanism of Immediate Analgesia Induced by Tuina Intervention on Minor Chronic Constriction Injury in Rats Using LC-MS.Journal of pain research · 2024Article
- GPR35 and mediators from platelets and mast cells in neutrophil migration and inflammation.Immunological reviews · 2023Review
- Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review.World journal of clinical cases · 2023Review
- GPR35 acts a dual role and therapeutic target in inflammation.Frontiers in immunology · 2023Review
- Migraine signaling pathways: amino acid metabolites that regulate migraine and predispose migraineurs to headache.Molecular and cellular biochemistry · 2022Review
- Organic anion transporter 1 is an HDAC4-regulated mediator of nociceptive hypersensitivity in mice.Nature communications · 2022Article
- Article
- Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period.The journal of headache and pain · 2021Article
- Neuroprotective effects of HTR1A antagonist WAY-100635 on scopolamine-induced delirium in rats and underlying molecular mechanisms.BMC neuroscience · 2016Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe role of serotonin (5-hydroxytrptamine, 5-HT) in the modulation of pain has been widely studied. Previous work led to the hypothesis that 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, might by itself influence pain thresholds.
resultsIn the present study, we investigated the role of 5-HIAA in inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) into the hind paw of mice. Wild-type mice were compared to mice deficient of the 5-HT transporter (5-HTT-/- mice) using behavioral tests for hyperalgesia and high-performance liquid chromatography (HPLC) to determine tissue levels of 5-HIAA. Wild-type mice reproducibly developed thermal hyperalgesia and paw edema for 5 days after CFA injection. 5-HTT-/- mice treated with CFA had reduced thermal hyperalgesia on day 1 after CFA injection and normal responses to heat thereafter. The 5-HIAA levels in spinal cord and sciatic nerve as measured with HPLC were lower in 5-HTT-/- mice than in wild-type mice after CFA injection. Pretreatment of wild-type mice with intraperitoneal injection of para-chlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, resulted in depletion of the 5-HIAA content in spinal cord and sciatic nerve and decrease in thermal hyperalgesia in CFA injected mice. The application of exogenous 5-HIAA resulted in potentiation of thermal hyperalgesia induced by CFA in 5-HTT-/- mice and in wild-type mice pretreated with p-CPA, but not in wild-type mice without p-CPA pretreatment. Further, methysergide, a broad-spectrum serotonin receptor antagonist, had no effect on 5-HIAA-induced potentiation of thermal hyperalgesia in CFA-treated wild-type mice.
conclusionTaken together, the present results suggest that 5-HIAA plays an important role in modulating peripheral thermal hyperalgesia in CFA induced inflammation, probably via a non-serotonin receptor mechanism.
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