In vivo priming and ex vivo activation of equine neutrophils in black walnut extract-induced equine laminitis is not attenuated by systemic lidocaine administration.
Abstract: Laminitis is a crippling disease of horses characterized by an inflammatory response in the tissue that suspends the axial skeleton within the hoof. Pain is a common feature of laminitic pathology and its management is an important component of the treatment regime for this disease. Systemic lidocaine administration is commonly utilized to manage pain in equine laminitis; however, the potential anti-inflammatory effects of this drug during the treatment of equine laminitis have not been investigated. Here, we sought to determine if lidocaine concentrations achieved in the plasma (therapeutic concentrations) of horses systemically administered lidocaine are capable of attenuating neutrophil activation and associated inflammation. To identify markers of activation, purified neutrophils were stimulated in vitro with LPS or recombinant equine IL-8 (reqIL-8) and surface expression of CD13 and CD18 was ascertained by immunofluorescent staining. Activation with LPS or reqIL-8 in vitro induced an elevated expression of CD13 as well as a putative conformational change in CD18 detected by elevated staining with a sub-saturating concentration of anti-CD18 mAb. Lidocaine attenuated the activation-induced changes in CD13 and CD18 expression only when used at 30-70 times therapeutic concentrations. For in vivo analyses, horses were administered black walnut extract (BWE) to induce laminitis and either systemic lidocaine (n=6) or saline (n=6) as a control. Whole blood was collected and incubated with or without reqIL-8. Following which, leukocytes were stained for CD13 and CD18. Protein was extracted from laminar tissue and subjected to gelatin zymography to measure matrix metalloproteinase-9 (MMP-9) accumulation. Results obtained show that changes in neutrophil size, granularity/complexity, CD13 surface expression and CD18 staining intensity occurred over time post BWE administration irrespective of lidocaine treatment in response to incubation alone or with 100 ng/ml of reqIL-8. The mean fluorescence intensities of neutrophils stained for either CD13 or CD18 did not differ between lidocaine treated and saline controls, nor did lamellar MMP-9 content measured by gelatin zymography. Thus, using changes in surface expression of CD13 and CD18 as markers of neutrophil activation in the horse we have shown that BWE treatment activates neutrophils in vivo and this is not affected by systemic administration of lidocaine at levels used to manage pain.
Copyright © 2010 Elsevier B.V. All rights reserved.
Publication Date: 2010-06-30 PubMed ID: 20667603DOI: 10.1016/j.vetimm.2010.06.016Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research aims to investigate the effectiveness of lidocaine, a medication often used for pain management in horses suffering from laminitis, in addressing the activation of neutrophils and related inflammation. Results showed that while lidocaine can aid in pain management, it does not significantly impact the inflammatory response associated with laminitis, even when used at therapeutic levels.
Understanding Laminitis and the Role of Lidocaine
- Laminitis is a severe disease in horses resulting in an inflammatory response within the hoof tissue. It typically causes significant pain, and its management forms a critical part of treatment protocols for the condition.
- Lidocaine is commonly administered systemically to manage this pain, but its potential anti-inflammatory effects have not been thoroughly examined.
Methodology and Experimental Design
- The research focused on whether therapeutic concentrations of lidocaine in horses’ plasma could mitigate neutrophil activation and the associated inflammation.
- Markers of neutrophil activation were identified by stimulating purified neutrophils in vitro with a potent immune-response elicitor, LPS, or with an equine immune-response protein, IL-8. The expression of CD13 and CD18 on the surface of these cells was then measured.
- In vivo analyses were conducted where horses were administered black walnut extract to induce laminitis and, subsequently, systemic lidocaine or a saline control.
- Leukocytes were stained for CD13 and CD18, and protein from laminar tissue was analyzed to measure the accumulation of a neutrophil enzyme, MMP-9.
Key Findings
- Changes in neutrophil size, complexity, CD13 surface expression and CD18 staining intensityoccurred over time post black walnut extract administration irrespective of lidocaine treatment.
- The intensities of neutrophils stained for either CD13 or CD18 did not differ between the samples treated with lidocaine and saline controls, nor did lamellar MMP-9 content.
- These results indicate that while lidocaine can help in managing pain, it does not significantly affect the inflammation caused by the activation of neutrophils.
Therefore, the research provided valuable insights into the use of lidocaine for treating laminitis in horses. While it remains a valuable tool for pain management, its effectiveness against the inflammation that characterizes the disease is not substantial. These findings highlight the need for additional strategies to control the inflammatory responses in laminitics.
Cite This Article
APA
Loftus JP, Williams JM, Belknap JK, Black SJ.
(2010).
In vivo priming and ex vivo activation of equine neutrophils in black walnut extract-induced equine laminitis is not attenuated by systemic lidocaine administration.
Vet Immunol Immunopathol, 138(1-2), 60-69.
https://doi.org/10.1016/j.vetimm.2010.06.016 Publication
Researcher Affiliations
- Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA. jpl249@cornell.edu
MeSH Terms
- Anesthetics, Local / administration & dosage
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
- CD13 Antigens / metabolism
- CD18 Antigens / metabolism
- Foot Diseases / chemically induced
- Foot Diseases / drug therapy
- Foot Diseases / immunology
- Foot Diseases / veterinary
- Gelatinases / metabolism
- Hoof and Claw
- Horse Diseases / chemically induced
- Horse Diseases / drug therapy
- Horse Diseases / immunology
- Horses / immunology
- In Vitro Techniques
- Juglans
- Lidocaine / administration & dosage
- Neutrophil Activation / drug effects
- Neutrophils / drug effects
- Neutrophils / immunology
- Pain / drug therapy
- Plant Extracts / toxicity
Citations
This article has been cited 3 times.- Miró J, Catalán J, Marín H, Yánez-Ortiz I, Yeste M. Specific Seminal Plasma Fractions Are Responsible for the Modulation of Sperm-PMN Binding in the Donkey. Animals (Basel) 2021 May 13;11(5).
- Miró J, Marín H, Catalán J, Papas M, Gacem S, Yeste M. Seminal Plasma, Sperm Concentration, and Sperm-PMN Interaction in the Donkey: An In Vitro Model to Study Endometrial Inflammation at Post-Insemination. Int J Mol Sci 2020 May 14;21(10).
- Wu YY, Chen MS, Chen IC, Wu FH, Liao TL, Wen HW, Nielsen BL, Liu HJ. Lidocaine Modulates Cytokine Production and Reprograms the Tumor Immune Microenvironment to Enhance Anti-Tumor Immune Responses in Gastric Cancer. Int J Mol Sci 2025 Mar 31;26(7).
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