FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Vet Intern Med / Serum nerve growth factor in horses with osteoarthritis-asso...
Journal of veterinary internal medicine2023; 37(3); 1201-1208; doi: 10.1111/jvim.16718

Serum nerve growth factor in horses with osteoarthritis-associated lameness.

Abstract: Nerve growth factor (NGF) is a neurotrophin that is increased in osteoarthritic joints of horses. In humans, NGF has been associated with pain, and both synovial and serum NGF concentrations are increased in osteoarthritic patients. Studies in humans also have shown that serum NGF concentration can increase with stress. Serum NGF concentration should be evaluated in horses with osteoarthritis-associated lameness. Objective: Quantify and compare serum NGF concentration in horses with osteoarthritis-associated lameness and sound horses. Additionally, the impact of short-term stress on serum NGF concentration was investigated. Methods: Lame horses with radiographic evidence of osteoarthritis (n = 20), lame horses without radiographic changes in the affected joint (n = 20) and sound horses (n = 20). In addition, horses with acute fractures (n = 9) were sampled. To determine the effect of stress, serum from horses subjected to a stressful event (transportation, n = 5; stress confirmed by increased serum cortisol concentration) was analyzed. Methods: Cross-sectional clinical study (lame, sound, and fracture cohorts) and experimental longitudinal study (stress cohort). Serum NGF concentration was determined using a quantitative sandwich ELISA. Results: Serum NGF concentration was increased in lame horses with radiographic evidence of osteoarthritis (P < .0001; median, 238 pg/mL; interquartile range [IQR], 63-945 pg/mL) and in lame horses without radiographic evidence of osteoarthritis in the painful joint (P < .05; median, 31 pg/mL; IQR, 31-95 pg/mL) compared with sound horses (median, 31 pg/mL; IQR, 31-46 pg/mL). Serum NGF concentration did not increase with short-term stress and was low in horses with fracture-associated pain. Conclusions: Serum NGF concentration was high in the cohort with advanced osteoarthritis and should be investigated as a marker for osteoarthritis-associated pain.
© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.
Get Full Text
Publication Date: 2023-04-21 PubMed ID: 37083137PubMed Central: PMC10229367DOI: 10.1111/jvim.16718Google 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.
LinkedInCopy
  • Journal Article

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.

This research investigates the presence and levels of Nerve Growth Factor (NGF), a protein associated with pain, in the blood of horses with osteoarthritic lameness. The study found elevated levels of NGF in lame horses, particularly those with advanced osteoarthritis, suggesting NGF could serve as a marker for this condition, while short-term stress did not impact NGF concentration.

Objective

The primary goal of this research was to measure and compare the concentration of Nerve Growth Factor (NGF) in the blood serum of horses suffering from osteoarthritis-associated lameness with healthy, sound horses. The secondary objective was to study the effect of short-term stress on NGF levels.

  • NGF is a protein that’s found at higher levels in osteoarthritic joint tissue.
  • In human studies, NGF has been linked with increasing pain levels and is found more in patients with osteoarthritis.
  • Previous work on humans indicated that NGF concentration in the bloodstream can increase due to stress.

Methods

Different groups of horses were examined as part of a cross-sectional clinical study and an experimental longitudinal analysis.

  • The subjects consisted of lame horses showing radiographic signs of osteoarthritis, lame horses with no radiographic changes, healthy horses and horses with acute fractures.
  • A separate group of horses was subjected to a stressful event (transportation) to see how this affected their NGF levels.
  • The concentration of NGF in the horses’ blood serum was determined using a quantitative sandwich ELISA, a test that measures the amount of a specific protein in a sample.

Results

The study showed increased NGF concentration in the blood of lame horses, especially those displaying radiographic signs of osteoarthritis.

  • Higher-than-normal NGF was found in horses diagnosed with osteoarthritis and in lame horses without joint changes evident from radiographic data.
  • Short-term stress did not result in increased NGF levels, contrary to results from human studies.
  • Horses suffering fractures did not show elevated NGF levels either.

Conclusions

The results suggest that blood serum NGF concentration is significantly high in horses with advanced osteoarthritis.

  • The high concentration of NGF in the blood of osteoarthritic horses indicates it could potentially serve as a marker for osteoarthritis-related pain in horses.
  • The distinct lack of increased NGF in lame horses without radiographic evidence of osteoarthritis suggests the protein’s increase is directly related to the disease rather than just lameness.
  • The fact that stress did not elevate NGF levels points to the protein as a specific marker for osteoarthritis, regardless of outside factors.

Cite This Article

APA
Kendall A, Lützelschwab C, Lundblad J, Skiöldebrand E. (2023). Serum nerve growth factor in horses with osteoarthritis-associated lameness. J Vet Intern Med, 37(3), 1201-1208. https://doi.org/10.1111/jvim.16718

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 37
Issue: 3
Pages: 1201-1208

Researcher Affiliations

Kendall, Anna
  • Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Lützelschwab, Claudia
  • Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Lundblad, Johan
  • Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Skiöldebrand, Eva
  • Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.

MeSH Terms

  • Humans
  • Animals
  • Horses
  • Longitudinal Studies
  • Lameness, Animal
  • Cross-Sectional Studies
  • Nerve Growth Factor
  • Horse Diseases / metabolism
  • Osteoarthritis / complications
  • Osteoarthritis / veterinary
  • Pain / veterinary

Grant Funding

  • 2019-02069 / Svenska Forskningsru00e5det Formas

Conflict of Interest Statement

Authors declare no conflict of interest.

References

This article includes 38 references
  1. de Grauw JC, van Loon JP. Systematic pain assessment in horses.. Vet J 2016 Mar;209:14-22.
    pubmed: 26831169doi: 10.1016/j.tvjl.2015.07.030google scholar: lookup
  2. Dyson S, Berger JM, Ellis AD, Mullard J. Behavioral observations and comparisons of nonlame horses and lame horses before and after resolution of lameness by diagnostic analgesia. J Vet Behav 2018;26:64‐70.
  3. LEVI-MONTALCINI R, HAMBURGER V. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo.. J Exp Zool 1951 Mar;116(2):321-61.
    pubmed: 14824426doi: 10.1002/jez.1401160206google scholar: lookup
  4. Levi-Montalcini R. The nerve growth factor 35 years later.. Science 1987 Sep 4;237(4819):1154-62.
    pubmed: 3306916doi: 10.1126/science.3306916google scholar: lookup
  5. Minnone G, De Benedetti F, Bracci-Laudiero L. NGF and Its Receptors in the Regulation of Inflammatory Response.. Int J Mol Sci 2017 May 11;18(5).
    pmc: PMC5454940pubmed: 28492466doi: 10.3390/ijms18051028google scholar: lookup
  6. Rukwied R, Mayer A, Kluschina O, Obreja O, Schley M, Schmelz M. NGF induces non-inflammatory localized and lasting mechanical and thermal hypersensitivity in human skin.. Pain 2010 Mar;148(3):407-413.
    pubmed: 20022698doi: 10.1016/j.pain.2009.11.022google scholar: lookup
  7. Minde J, Toolanen G, Andersson T, Nennesmo I, Remahl IN, Svensson O, Solders G. Familial insensitivity to pain (HSAN V) and a mutation in the NGFB gene. A neurophysiological and pathological study.. Muscle Nerve 2004 Dec;30(6):752-60.
    pubmed: 15468048doi: 10.1002/mus.20172google scholar: lookup
  8. Montagnoli C, Tiribuzi R, Crispoltoni L, Pistilli A, Stabile AM, Manfreda F, Placella G, Rende M, Cerulli GG. β-NGF and β-NGF receptor upregulation in blood and synovial fluid in osteoarthritis.. Biol Chem 2017 Aug 28;398(9):1045-1054.
    pubmed: 28253191doi: 10.1515/hsz-2016-0280google scholar: lookup
  9. Chandran V, Abji F, Perruccio AV, Gandhi R, Li S, Cook RJ, Gladman DD. Serum-based soluble markers differentiate psoriatic arthritis from osteoarthritis.. Ann Rheum Dis 2019 Jun;78(6):796-801.
    pubmed: 30910989doi: 10.1136/annrheumdis-2018-214737google scholar: lookup
  10. Clauw DJ, Hassett AL. The role of centralised pain in osteoarthritis.. Clin Exp Rheumatol 2017 Sep-Oct;35 Suppl 107(5):79-84.
    pubmed: 28967359
  11. Dakin P, DiMartino SJ, Gao H, Maloney J, Kivitz AJ, Schnitzer TJ, Stahl N, Yancopoulos GD, Geba GP. The Efficacy, Tolerability, and Joint Safety of Fasinumab in Osteoarthritis Pain: A Phase IIb/III Double-Blind, Placebo-Controlled, Randomized Clinical Trial.. Arthritis Rheumatol 2019 Nov;71(11):1824-1834.
    pmc: PMC6900077pubmed: 31207169doi: 10.1002/art.41012google scholar: lookup
  12. Corral MJ, Moyaert H, Fernandes T, Escalada M, Kira S Tena J, Walters RR, Stegemann MR. A prospective, randomized, blinded, placebo-controlled multisite clinical study of bedinvetmab, a canine monoclonal antibody targeting nerve growth factor, in dogs with osteoarthritis.. Vet Anaesth Analg 2021 Nov;48(6):943-955.
    pubmed: 34565678doi: 10.1016/j.vaa.2021.08.001google scholar: lookup
  13. Gruen ME, Myers JAE, Tena JS, Becskei C, Cleaver DM, Lascelles BDX. Frunevetmab, a felinized anti-nerve growth factor monoclonal antibody, for the treatment of pain from osteoarthritis in cats.. J Vet Intern Med 2021 Nov;35(6):2752-2762.
    pmc: PMC8692178pubmed: 34724255doi: 10.1111/jvim.16291google scholar: lookup
  14. Aloe L, Bracci-Laudiero L, Alleva E, Lambiase A, Micera A, Tirassa P. Emotional stress induced by parachute jumping enhances blood nerve growth factor levels and the distribution of nerve growth factor receptors in lymphocytes.. Proc Natl Acad Sci U S A 1994 Oct 25;91(22):10440-4.
    pmc: PMC45036pubmed: 7937971doi: 10.1073/pnas.91.22.10440google scholar: lookup
  15. Aloe L, Alleva E, Böhm A, Levi-Montalcini R. Aggressive behavior induces release of nerve growth factor from mouse salivary gland into the bloodstream.. Proc Natl Acad Sci U S A 1986 Aug;83(16):6184-7.
    pmc: PMC386464pubmed: 3090553doi: 10.1073/pnas.83.16.6184google scholar: lookup
  16. Dyson S. Can lameness be graded reliably?. Equine Vet J 2011 Jul;43(4):379-82.
    pubmed: 21631579doi: 10.1111/j.2042-3306.2011.00391.xgoogle scholar: lookup
  17. May ML, Nolen-Walston RD, Utter ME, Boston RC. Comparison of hematologic and biochemical results on blood obtained by jugular venipuncture as compared with intravenous catheter in adult horses.. J Vet Intern Med 2010 Nov-Dec;24(6):1462-6.
    pubmed: 20738771doi: 10.1111/j.1939-1676.2010.0582.xgoogle scholar: lookup
  18. Aso K, Shahtaheri SM, Hill R, Wilson D, McWilliams DF, Walsh DA. Associations of Symptomatic Knee Osteoarthritis With Histopathologic Features in Subchondral Bone.. Arthritis Rheumatol 2019 Jun;71(6):916-924.
    pubmed: 30663865doi: 10.1002/art.40820google scholar: lookup
  19. Kendall A, Nyström S, Ekman S, Hultén LM, Lindahl A, Hansson E, Skiöldebrand E. Nerve growth factor in the equine joint.. Vet J 2021 Jan;267:105579.
    pubmed: 33375964doi: 10.1016/j.tvjl.2020.105579google scholar: lookup
  20. Aso K, Walsh DA, Wada H, Izumi M, Tomitori H, Fujii K, Ikeuchi M. Time course and localization of nerve growth factor expression and sensory nerve growth during progression of knee osteoarthritis in rats.. Osteoarthritis Cartilage 2022 Oct;30(10):1344-1355.
    pubmed: 35843479doi: 10.1016/j.joca.2022.07.003google scholar: lookup
  21. Hirth M, Rukwied R, Gromann A, Turnquist B, Weinkauf B, Francke K, Albrecht P, Rice F, Hägglöf B, Ringkamp M, Engelhardt M, Schultz C, Schmelz M, Obreja O. Nerve growth factor induces sensitization of nociceptors without evidence for increased intraepidermal nerve fiber density.. Pain 2013 Nov;154(11):2500-2511.
    pubmed: 23891896doi: 10.1016/j.pain.2013.07.036google scholar: lookup
  22. Jones MG, Munson JB, Thompson SWN. A role for nerve growth factor in sympathetic sprouting in rat dorsal root ganglia.. Pain 1999 Jan;79(1):21-29.
    pubmed: 9928772doi: 10.1016/s0304-3959(98)00142-0google scholar: lookup
  23. Miller RE, Tran PB, Ishihara S, Syx D, Ren D, Miller RJ, Valdes AM, Malfait AM. Microarray analyses of the dorsal root ganglia support a role for innate neuro-immune pathways in persistent pain in experimental osteoarthritis.. Osteoarthritis Cartilage 2020 May;28(5):581-592.
    pmc: PMC7214125pubmed: 31982564doi: 10.1016/j.joca.2020.01.008google scholar: lookup
  24. Sousa-Valente J, Calvo L, Vacca V, Simeoli R, Arévalo JC, Malcangio M. Role of TrkA signalling and mast cells in the initiation of osteoarthritis pain in the monoiodoacetate model.. Osteoarthritis Cartilage 2018 Jan;26(1):84-94.
    pubmed: 28844566doi: 10.1016/j.joca.2017.08.006google scholar: lookup
  25. Ashraf S, Mapp PI, Burston J, Bennett AJ, Chapman V, Walsh DA. Augmented pain behavioural responses to intra-articular injection of nerve growth factor in two animal models of osteoarthritis.. Ann Rheum Dis 2014 Sep;73(9):1710-8.
    pmc: PMC4145450pubmed: 23852764doi: 10.1136/annrheumdis-2013-203416google scholar: lookup
  26. Hochberg MC. Serious joint-related adverse events in randomized controlled trials of anti-nerve growth factor monoclonal antibodies.. Osteoarthritis Cartilage 2015 Jan;23 Suppl 1:S18-21.
    pubmed: 25527216doi: 10.1016/j.joca.2014.10.005google scholar: lookup
  27. Arendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, Graven-Nielsen T. Sensitization in patients with painful knee osteoarthritis.. Pain 2010 Jun;149(3):573-581.
    pubmed: 20418016doi: 10.1016/j.pain.2010.04.003google scholar: lookup
  28. Greve L, Dyson SJ. The interrelationship of lameness, saddle slip and back shape in the general sports horse population.. Equine Vet J 2014 Nov;46(6):687-94.
    pubmed: 24372949doi: 10.1111/evj.12222google scholar: lookup
  29. Gilbertson EM. Development of periarticular osteophytes in experimentally induced osteoarthritis in the dog. A study using microradiographic, microangiographic, and fluorescent bone-labelling techniques.. Ann Rheum Dis 1975 Feb;34(1):12-25.
    pmc: PMC1006340pubmed: 1124952doi: 10.1136/ard.34.1.12google scholar: lookup
  30. Minnone G, Soligo M, Caiello I, Prencipe G, Manni L, Marafon DP, Magni-Manzoni S, Manzo A, De Benedetti F, Bracci-Laudiero L. ProNGF-p75NTR axis plays a proinflammatory role in inflamed joints: a novel pathogenic mechanism in chronic arthritis.. RMD Open 2017;3(2):e000441.
    pmc: PMC5604749pubmed: 28955492doi: 10.1136/rmdopen-2017-000441google scholar: lookup
  31. Denk F, Bennett DL, McMahon SB. Nerve Growth Factor and Pain Mechanisms.. Annu Rev Neurosci 2017 Jul 25;40:307-325.
    pubmed: 28441116doi: 10.1146/annurev-neuro-072116-031121google scholar: lookup
  32. Sung K, Ferrari LF, Yang W, Chung C, Zhao X, Gu Y, Lin S, Zhang K, Cui B, Pearn ML, Maloney MT, Mobley WC, Levine JD, Wu C. Swedish Nerve Growth Factor Mutation (NGF(R100W)) Defines a Role for TrkA and p75(NTR) in Nociception.. J Neurosci 2018 Apr 4;38(14):3394-3413.
    pmc: PMC5895035pubmed: 29483280doi: 10.1523/jneurosci.1686-17.2018google scholar: lookup
  33. Soligo M, Protto V, Florenzano F, Bracci-Laudiero L, De Benedetti F, Chiaretti A, Manni L. The mature/pro nerve growth factor ratio is decreased in the brain of diabetic rats: Analysis by ELISA methods.. Brain Res 2015 Oct 22;1624:455-468.
    pubmed: 26282349doi: 10.1016/j.brainres.2015.08.005google scholar: lookup
  34. Ando I, Karasawa K, Matsuda H, Tanaka A. Changes in serum NGF levels after the exercise load in dogs: a pilot study.. J Vet Med Sci 2016 Dec 1;78(11):1709-1712.
    pmc: PMC5138426pubmed: 27452735doi: 10.1292/jvms.16-0258google scholar: lookup
  35. Ando I, Karasawa K, Shioya T, Matsuda H, Tanaka A. Evaluation of stress status using the stress map for guide dog candidates in the training stage using variations in the serum cortisol with nerve growth factor and magnesium ions.. Vet Anim Sci 2020 Dec;10:100129.
    pmc: PMC7386704pubmed: 32734029doi: 10.1016/j.vas.2020.100129google scholar: lookup
  36. Matsuda H, Koyama H, Oikawa M, Yoshihara T, Kaneko M. Nerve growth factor-like activity detected in equine peripheral blood after running exercise.. Zentralbl Veterinarmed A 1991 Aug;38(7):557-9.
    pubmed: 1950248doi: 10.1111/j.1439-0442.1991.tb01048.xgoogle scholar: lookup
  37. Gold SM, Schulz KH, Hartmann S, Mladek M, Lang UE, Hellweg R, Reer R, Braumann KM, Heesen C. Basal serum levels and reactivity of nerve growth factor and brain-derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls.. J Neuroimmunol 2003 May;138(1-2):99-105.
    pubmed: 12742659doi: 10.1016/s0165-5728(03)00121-8google scholar: lookup
  38. Kawamoto K, Sato H, Oikawa M. Nerve growth factor activity detected in equine peripheral blood of horses with fever after truck transportation. J Equine Sci 1996;7:43‐46.

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.