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

Background:
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.

Objectives:
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.

Study design:
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.

Main Limitations:
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.