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Circulating miR-23b-3p, miR-145-5p and miR-200b-3p are potential biomarkers to monitor acute pain associated with laminitis in horses.
Abstract: Circulating microRNAs (miRNAs) are emerging as promising biomarkers for several disorders and related pain. In equine practice, acute laminitis is a common disease characterised by intense pain that severely compromises horse welfare. Recently, the Horse Grimace Scale (HGS), a facial expression-based pain coding system, was shown to be a valid welfare indicator to identify pain linked to acute laminitis. The present study aimed to: determine whether miRNAs can be used as biomarkers for acute pain in horses (Equus caballus) affected by laminitis; integrate miRNAs to their target genes and to categorise target genes for biological processes; gather additional evidence on concurrent validity of HGS by investigating how it correlates to miRNAs. Nine horses presenting acute laminitis with no prior treatment were recruited. As control group, nine healthy horses were further included in the experimental design. Samples were collected from horses with laminitis at admission before any treatment ('pre-treatment') and 7 days after routine laminitis treatment ('post-treatment'). The expression levels of nine circulating miRNAs, namely hsa-miR-532-3p, hsa-miR-219-5p, mmu-miR-134-5p, mmu-miR-124a-3p, hsa-miR-200b-3p, hsa-miR-146a-5p, hsa-miR-23b-3p, hsa-miR-145-5p and hsa-miR-181a-5p, were detected and assessed as potential biomarkers of pain by quantitative PCR using TaqMan® probes. The area under the receiver operating curve (AUC) was then used to evaluate the diagnostic performance of miRNAs. Molecular data were integrated with HGS scores assessed by one trained treatment and time point blind veterinarian. The comparative analysis demonstrated that the levels of miR-23b-3p (P=0.029), miR-145-5p (P=0.015) and miR-200b-3p (P=0.023) were significantly higher in pre-treatment and the AUCs were 0.854, 0.859 and 0.841, respectively. MiR-200b-3p decreased after routine laminitis treatment (P=0.043). Combining two miRNAs in a panel, namely miR-145-5p and miR-200b-3p, increased efficiency in distinguishing animals with acute pain from controls. In addition, deregulated miRNAs were positively correlated to HGS scores. Computational target prediction and functional enrichment identified common biological pathways between different miRNAs. In particular, the glutamatergic pathway was affected by all three miRNAs, suggesting a crucial role in the pathogenesis of pain. In conclusion, the dynamic expression of circulating miR-23b-3p, miR-145-5p and miR-200b-3p was detected in horses with acute laminitis and miRNAs can be considered potentially promising pain biomarkers. Further studies are needed in order to assess their relevancy in other painful conditions severely compromising horse welfare. An important implication would be the possibility to use them for the concurrent validation of non-invasive indicators of pain in horses.
Publication Date: 2017-07-10 PubMed ID: 28689512DOI: 10.1017/S1751731117001525Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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This research seeks to identify microRNAs (miRNAs) that could serve as possible indicators of acute pain in horses suffering from laminitis, a painful hoof condition. The study further explores these miRNAs’ correlation with the Horse Grimace Scale, a method for pain evaluation based on facial expressions.
Objective and Background
- The primary intention of this study was to discover if specific miRNAs could be established as biomarkers for acute pain in horses affected by laminitis, a painful and common hoof disease.
- miRNAs are small non-coding RNA molecules that have emerged as potential biomarkers for multiple disorders due to their role in regulating gene expression.
- The research, notably, also aspired to accumulate more evidence on the concurrent validity of the Horse Grimace Scale (HGS), a scoring system based on the horse’s facial expressions, by studying its relationship with miRNAs.
Research Design and Methodology
- Nine laminitic horses with no prior treatment were included in the study, and a control group consisted of nine healthy horses. Samples were taken pre-treatment and post-treatment (7 days after ordinary laminitis treatment).
- Nine specific circulating miRNAs were examined for their potential as pain biomarkers using a quantitative PCR process with TaqMan® probes.
- The diagnostic performance of these miRNAs was evaluated by assessing the area under the receiver operating curve (AUC) and comparing miRNA levels with HGS scores assessed by a veterinarian blinded to treatment and time points.
Findings and Conclusion
- The study found that the levels of three miRNAs – miR-23b-3p, miR-145-5p, and miR-200b-3p – were significantly elevated in horses pre-treatment, and they decreased post-treatment.
- The combination of two miRNAs, miR-145-5p and miR-200b-3p, increased efficiency in distinguishing horses with acute pain from the control group.
- Furthermore, these deregulated miRNAs have positive correlations with HGS scores, which supports the HGS’s concurrent validity in gauging pain severity in horses.
- Functional enrichment and computational target prediction identified a common biological pathway, the glutamatergic pathway, between the various miRNAs, alluding to its potential critical role in pain pathogenesis.
- In conclusion, miRNAs have potential as viable pain biomarkers in horses suffering from acute laminitis, but future studies are required to verify these biomarkers’ applicability in other painful conditions that severely compromise horse welfare.
Cite This Article
APA
Lecchi C, Dalla Costa E, Lebelt D, Ferrante V, Canali E, Ceciliani F, Stucke D, Minero M.
(2017).
Circulating miR-23b-3p, miR-145-5p and miR-200b-3p are potential biomarkers to monitor acute pain associated with laminitis in horses.
Animal, 12(2), 366-375.
https://doi.org/10.1017/S1751731117001525 Publication
Researcher Affiliations
- 1Dipartimento di Medina Veterinaria,Università degli Studi di Milano,Via Celoria 10,20133 Milano,Italy.
- 1Dipartimento di Medina Veterinaria,Università degli Studi di Milano,Via Celoria 10,20133 Milano,Italy.
- 2Havelland Equine Clinic,14778 Beetzsee,Germany.
- 1Dipartimento di Medina Veterinaria,Università degli Studi di Milano,Via Celoria 10,20133 Milano,Italy.
- 1Dipartimento di Medina Veterinaria,Università degli Studi di Milano,Via Celoria 10,20133 Milano,Italy.
- 1Dipartimento di Medina Veterinaria,Università degli Studi di Milano,Via Celoria 10,20133 Milano,Italy.
- 2Havelland Equine Clinic,14778 Beetzsee,Germany.
- 1Dipartimento di Medina Veterinaria,Università degli Studi di Milano,Via Celoria 10,20133 Milano,Italy.
MeSH Terms
- Acute Pain / blood
- Acute Pain / diagnosis
- Acute Pain / pathology
- Acute Pain / veterinary
- Animal Welfare
- Animals
- Area Under Curve
- Biomarkers / blood
- Circulating MicroRNA / blood
- Circulating MicroRNA / genetics
- Female
- Foot Diseases / blood
- Foot Diseases / diagnosis
- Foot Diseases / pathology
- Foot Diseases / veterinary
- Hoof and Claw / pathology
- Horse Diseases / blood
- Horse Diseases / diagnosis
- Horse Diseases / pathology
- Horses
- Inflammation / veterinary
- Male
- Real-Time Polymerase Chain Reaction / veterinary
Citations
This article has been cited 14 times.- Lascelles BDX, Barratt D, Basran PS, Brown DC, Coetzee JF, Gill M, Hutchinson MR, Johnson C, Luna SPL, Mohapatra DP, Oshinsky ML, Robertson S, Ruberman CF, Smith ER, Zhang Q. Advancing outcome measure development and analytical approaches: Pain in Animals Workshop 2023. Front Pain Res (Lausanne) 2025;6:1615862.
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- Bardi E, Brizzola S, Ravasio G, Romussi S, Dall'Ara P, Zamarian V, Arigoni M, Calogero RA, Lecchi C. Circulating miRNome of Trachemys scripta after elective gonadectomy under general anesthesia. Sci Rep 2021 Jul 19;11(1):14712.
- Davies J, Thomas C, Rizwan M, Gwenin C. Development of Electrochemical DNA Biosensor for Equine Hindgut Acidosis Detection. Sensors (Basel) 2021 Mar 26;21(7).
- Lee S, Baker ME, Clinton M, Taylor SE. Use of Omics Data in Fracture Prediction; a Scoping and Systematic Review in Horses and Humans. Animals (Basel) 2021 Mar 30;11(4).
- Zhang P, Liu L, Yao L, Song X. Improved Differentiation Ability and Therapeutic Effect of miR-23a-3p Expressing Bone Marrow-Derived Mesenchymal Stem Cells in Mice Model with Acute Lung Injury. Int J Stem Cells 2021 May 30;14(2):229-239.
- Lecchi C, Zamarian V, Borriello G, Galiero G, Grilli G, Caniatti M, D'Urso ES, Roccabianca P, Perego R, Minero M, Legnani S, Calogero R, Arigoni M, Ceciliani F. Identification of Altered miRNAs in Cerumen of Dogs Affected by Otitis Externa. Front Immunol 2020;11:914.
- Lecchi C, Zamarian V, Gini C, Avanzini C, Polloni A, Rota Nodari S, Ceciliani F. Salivary microRNAs are potential biomarkers for the accurate and precise identification of inflammatory response after tail docking and castration in piglets. J Anim Sci 2020 May 1;98(5).
- Lecchi C, Catozzi C, Zamarian V, Poggi G, Borriello G, Martucciello A, Vecchio D, DeCarlo E, Galiero G, Ceciliani F. Characterization of circulating miRNA signature in water buffaloes (Bubalus bubalis) during Brucella abortus infection and evaluation as potential biomarkers for non-invasive diagnosis in vaginal fluid. Sci Rep 2019 Feb 13;9(1):1945.
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