Abstract
Abstract
Cranial cruciate ligament (CrCL) disease in dogs causes pain and osteoarthritis (OA) and surgical treatment does not prevent OA progression. Glutamate receptor (GluR) antagonists alleviate pain and degeneration in rodent models of OA, but it is unknown whether they are a suitable treatment for dogs. Understanding GluR signalling in CrCL disease may lead to novel therapeutics in both veterinary and human medicine.
Objectives
To determine whether age, breed, sex, weight, and therapeutic(s) influence lameness and pre-operative radiographic OA scoring in dogs with CrCL disease and whether GluRs are expressed, in this disease.
Methods
Surgical waste (CrCL and medial meniscus), clinical data, stifle radiographs, lameness scores (1–4, mild-unloading limb) were obtained with full informed consent (RCVS ethics approval, ref: 2017/14/Alves). OA scoring was performed on radiographs [VCOT, 2017, 30(6):377–384, 15–60, normal-severe OA], and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-2 and kainate (KA)-1 GluR expression compared in diseased versus control tissues by immunohistochemistry (IHC).
Results
We studied 25 dogs (various breeds, 4.88±3.02 years; 44% male; 56% female; 27.13±9.12kg). At the time of surgery, 44% dogs were on meloxicam alone, 40% on other therapeutic(s) and 16% on no therapeutics. Linear regression showed that OA score (mean 21.72±3.47) did not correlate with lameness score (mean 1.98±1.08), age or weight (p values of 0.7483, 0.4597, 0.1463; R2 values of 0.004563, 0.02400, 0.08951, respectively). Radiographic OA scores and lameness scores did not differ between therapeutic groups (one-way ANOVA, p=0.9229 and p=0.5541, respectively). GluRs (AMPA-2/KA-1) were expressed in CrCL and medial meniscus, with increased labelling in the CrCL epiligamentous region in diseased tissues, where microanatomy was disrupted.
Conclusions
In this population, OA scores do not correlate with lameness scores, age, weight, and therapeutics at the time of surgery. Variable GluR expression in diseased tissues implicates glutamate signalling in this pathology.
Declaration of Interest
(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.