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W18-028: Master regulator of DJD-associated pain and hypersensitivity in felines

Degenerative joint disease (DJD), a term which includes osteoarthritis, and the associated pain in cats, is a poorly understood disease. Cats with DJD-pain have trouble moving, trouble performing activities of daily living. Widespread sensitivity to stimuli is hallmark of arthritis and DJD-associated pain in cats, and contributes to the pain condition. Little is known about the mechanisms driving this pain in cats, and untreated pain results in increased sensitivity and more debilitating pain. By using the novel approach of looking at tissues from pets with real DJD-pain (as opposed to induced pain in rodent models), the investigators have uncovered an important driving mechanism that has been hitherto ignored. A receptor called GFRA3 is found in the neurons that that respond to painful stimuli. A protein called artemin binds to GFRA3 and changes how these neurons respond by increasing their sensitivity and recruiting other neurons to engage in heightened pain processing. They have early data to indicate that GFRA3 plays a prominent role in chronic pain in the cat. Additionally, the features of GFRA3 and artemin suggest this could be the reason for the dramatic increase in sensitivity to pain often seen in cats with DJD-pain (and other chronically painful conditions). With no approved drugs to treat osteoarthritis pain in cats, and very little in the way of proven therapies, the research they are proposing is crucial and has the potential to catapult clinicians towards being able to effectively control DJD-pain in these wonderful companions.

Grant ID: W18-028

Status: Active

Year Funded: 2018

Amount awarded: $23,560

Investigator: Santosh Mishra, PhD and Duncan Lascelles, BVSc, PhD, DACVS; North Carolina State University