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Equine veterinary journal2025; doi: 10.1002/evj.70139

Calcitonin gene-related peptide concentration in cerebrospinal fluid and serum in horses affected by trigeminal-mediated headshaking.

Abstract: Trigeminal-mediated headshaking (TMHS) in horses shares clinical features with human trigeminal neuralgia (HTN). Increased levels of the neuropeptide calcitonin gene-related peptide (CGRP) have been found in the blood and cerebrospinal fluid (CSF) of HTN patients. Inhibition of CGRP in humans has shown promise for pain relief. Data on CGRP in horses affected by TMHS are currently lacking but if quantifiable and validated, could assist in developing new diagnostic and more rational therapeutic approaches. Objective: This study aimed to quantify and correlate CGRP concentrations in the serum and CSF of horses with TMHS; compare CSF CGRP levels across horses with various neurological, painful, inflammatory and chronic conditions; analyse serum CGRP concentrations before and after exercise-induced headshaking in affected horses versus healthy controls. Methods: Case-control study using bio-banked samples and prospective before-after study. Methods: CGRP concentrations were measured in CSF and serum using a commercial ELISA kit across healthy controls (CONTROL, n = 5), TMHS-affected horses (n = 30), horses with cervical vertebral stenotic myelopathy (CVSM, n = 10) and horses with non-neurologic painful, inflammatory or chronic conditions (MIXED, n = 8). Results: Median (interquartile range [IQR]) serum CGRP concentration in TMHS horses was 14.9 pg/mL (11.3-19.0 pg/mL), while mean ± SD CGRP CSF concentration was 64.9 ± 6.3 pg/mL. No correlation was found between serum and CSF CGRP (Spearman's rho = -0.04, p = 0.88). CSF CGRP levels were significantly higher in CVSM (73.8 pg/mL; p = 0.011) and lower in MIXED (52.0 pg/mL; p = 0.001) compared to TMHS. Serum CGRP concentrations showed no significant difference between TMHS and CONTROL groups. Conclusions: Small sample size, lack of CSF samples from healthy controls. Conclusions: Higher CSF CGRP levels in neurologic conditions may suggest shared underlying mechanisms such as nerve irritation or neuroinflammation. Further research is needed to elucidate CGRP's role in TMHS pathophysiology.
© 2025 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2025-12-19 PubMed ID: 41416948DOI: 10.1002/evj.70139Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study investigated the levels of calcitonin gene-related peptide (CGRP) in the cerebrospinal fluid (CSF) and serum of horses suffering from trigeminal-mediated headshaking (TMHS), a condition similar to human trigeminal neuralgia.
  • The research aimed to understand if CGRP could serve as a biomarker or therapeutic target by comparing its concentration in affected horses and those with other neurological or inflammatory diseases, as well as in healthy controls.

Introduction

  • Trigeminal-mediated headshaking (TMHS) in horses is a painful condition characterized by sudden, repetitive head movements, thought to be linked to abnormal trigeminal nerve activity.
  • Human trigeminal neuralgia (HTN) exhibits similar symptoms and is associated with increased levels of the neuropeptide CGRP in blood and CSF.
  • CGRP plays a role in pain transmission and neuroinflammation; inhibition of CGRP has shown promise in alleviating pain in humans.
  • Currently, data on CGRP involvement in horses with TMHS is lacking, but quantification of CGRP could help in diagnosing and developing targeted treatments.

Objectives

  • Quantify CGRP concentrations in serum and CSF of horses affected by TMHS.
  • Compare CSF CGRP levels among horses with various neurological (cervical vertebral stenotic myelopathy – CVSM), painful/inflammatory, and chronic conditions.
  • Assess serum CGRP concentrations before and after exercise-induced headshaking in affected horses compared to healthy controls.

Methods

  • Study design included a case-control component and a prospective before-after component using bio-banked and fresh samples.
  • Sample groups included:
    • TMHS-affected horses (n=30)
    • Healthy control horses (CONTROL, n=5)
    • Horses with cervical vertebral stenotic myelopathy (CVSM, n=10)
    • Horses with non-neurologic painful, inflammatory, or chronic conditions (MIXED, n=8)
  • CGRP levels were measured in CSF and serum using a commercial enzyme-linked immunosorbent assay (ELISA) kit.
  • Correlations between serum and CSF CGRP levels, as well as differences between groups, were statistically analyzed.

Results

  • Median serum CGRP concentration in TMHS horses was 14.9 pg/mL (interquartile range 11.3-19.0 pg/mL).
  • Mean CSF CGRP concentration in TMHS horses was 64.9 ± 6.3 pg/mL.
  • There was no significant correlation between serum and CSF CGRP concentrations in TMHS horses (Spearman’s rho = -0.04, p = 0.88), indicating independent fluctuations in these compartments.
  • When comparing CSF CGRP levels across groups:
    • CVSM horses had significantly higher CSF CGRP concentrations (73.8 pg/mL, p = 0.011) compared to TMHS horses.
    • Horses with painful, inflammatory, or chronic conditions (MIXED group) had significantly lower CSF CGRP levels (52.0 pg/mL, p = 0.001) compared to TMHS horses.
  • Serum CGRP concentrations showed no significant difference between TMHS horses and healthy controls.

Conclusions

  • The study revealed elevated CSF CGRP levels in horses with neurologic conditions such as TMHS and CVSM, suggesting that neuropeptide changes in CSF might reflect underlying nerve irritation or neuroinflammation associated with these diseases.
  • The lack of correlation between serum and CSF CGRP suggests that serum CGRP is not a reliable biomarker for central nervous system CGRP dynamics in TMHS.
  • There was no significant difference in serum CGRP between TMHS and healthy horses, indicating peripheral blood CGRP might not reflect disease state in TMHS.
  • The relatively small sample size and absence of CSF samples from healthy controls limit the interpretation and generalizability of the findings.
  • Overall, the findings support further research to clarify CGRP’s role in TMHS pathophysiology, which may help develop improved diagnostic markers or therapies targeting the CGRP pathway.

Cite This Article

APA
Weber LA, Oltmanns H, Chiavaccini L, Pickles KJ, Roberts V, Kloock T, Niebuhr T, Feige K. (2025). Calcitonin gene-related peptide concentration in cerebrospinal fluid and serum in horses affected by trigeminal-mediated headshaking. Equine Vet J. https://doi.org/10.1002/evj.70139

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Weber, Lisa Annabel
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Oltmanns, Hilke
  • Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Chiavaccini, Ludovica
  • Department of Comparative Diagnostic and Population Medicine, University of Florida, Gainesville, Florida, USA.
Pickles, Kirstie J
  • Harper & Keele Veterinary School, Keele Campus, Staffordshire, UK.
Roberts, Veronica
  • Bristol Veterinary School, University of Bristol, Langford, Bristol, UK.
Kloock, Tanja
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
  • Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Niebuhr, Tobias
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
  • Equine Clinic Nindorf, Hanstedt, Germany.
Feige, Karsten
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.

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