01985: Defining Novel Drug Targets to Treat Chronic and Neuropathic Pain in the Dog

Grant Status: Closed

Grant Amount: $69,128
Ronald Sluyter, PhD; University of Wollongong
January 1, 2014 - December 31, 2015

Sponsor(s): Westie Foundation of America, Inc.

Breed(s): -All Dogs
Research Program Area: Neurology
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Project Summary

Chronic or long-lasting pain is a major health problem and welfare issue in dogs. Chronic pain results from disease, injury or aging. Evidence from humans and rodents strongly implicates an important role for a group of molecules (termed P2X receptors) on white blood cells (within the bone joints, spinal cord and other body parts) in chronic pain. The roles of P2X receptors in dogs however remain poorly understood. Therefore, the proposed project aims to determine the roles of these receptors and how they contribute to chronic pain in dogs. Improved understanding of the factors that contribute to chronic pain will greatly aid in the development of new approaches and drugs to alleviate or treat chronic pain in dogs. We have determined that dogs express P2X4 receptors and that the gene coding this receptor is highly conserved between dogs, suggesting it may be a potential drug target to treat chronic pain in these animals.

Publication(s)

Sophocleous, R. A., Miles, N. A., Ooi, L., & Sluyter, R. (2020). P2Y2 and P2X4 Receptors Mediate Ca2+ Mobilization in DH82 Canine Macrophage Cells. International Journal of Molecular Sciences, 21(22), 8572. https://doi.org/10.3390/ijms21228572

Sophocleous, R. A., Berg, T., Finol‐Urdaneta, R. K., Sluyter, V., Keshiya, S., Bell, L., Curtis, S. J., Curtis, B. L., Seavers, A., Bartlett, R., Dowton, M., Stokes, L., Ooi, L., & Sluyter, R. (2020). Pharmacological and genetic characterisation of the canine P2X4 receptor. British Journal of Pharmacology, 177(12), 2812–2829. https://doi.org/10.1111/bph.15009

Bartlett, R., Stokes, L., & Sluyter, R. (2014). The P2X7 Receptor Channel: Recent Developments and the Use of P2X7 Antagonists in Models of Disease. Pharmacological Reviews, 66(3), 638–675. https://doi.org/10.1124/pr.113.008003

Faulks, M., Kuit, T. A., Sophocleous, R. A., Curtis, B. L., Curtis, S. J., Jurak, L. M., & Sluyter, R. (2016). P2X7 receptor activation causes phosphatidylserine exposure in canine erythrocytes. World Journal of Hematology, 5(4), 88. https://doi.org/10.5315/wjh.v5.i4.88

Pupovac, A., & Sluyter, R. (2016). Roles of extracellular nucleotides and P2 receptors in ectodomain shedding. Cellular and Molecular Life Sciences, 73(22), 4159–4173. https://doi.org/10.1007/s00018-016-2274-2

Sluyter, R. (2015). P2X and P2Y receptor signaling in red blood cells. Frontiers in Molecular Biosciences, 2(60), 1–7. https://doi.org/10.3389/fmolb.2015.00060

Sophocleous, R. A., Sluyter, V., Curtis, B. L., Curtis, S. J., Jurak, L. M., Faulks, M., … Sluyter, R. (2019). Association of a P2RX7 gene missense variant with brachycephalic dog breeds. Animal Genetics. https://doi.org/10.1111/age.12884

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