With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.

Lack of validity in osteoarthritis pain models and assessment methods is suspected. Our goal was to 1) assess the repeatability and reproducibility of measurement and the influence of environment, and acclimatization, to different pain assessment outcomes in normal rats, and 2) test the concurrent validity of the most reliable methods in relation to the expression of different spinal neuropeptides in a chemical model of osteoarthritic pain. Repeatability and inter-rater reliability of reflexive nociceptive mechanical thresholds, spontaneous static weight-bearing, treadmill, rotarod, and operant place escape/avoidance paradigm (PEAP) were assessed by the intraclass correlation coefficient (ICC). The most reliable acclimatization protocol was determined by comparing coefficients of variation. In a pilot comparative study, the sensitivity and responsiveness to treatment of the most reliable methods were tested in the monosodium iodoacetate (MIA) model over 21 days. Two MIA (2 mg) groups (including one lidocaine treatment group) and one sham group (0.9 % saline) received an intra-articular (50 μL) injection. No effect of environment (observer, inverted circadian cycle, or exercise) was observed; all tested methods except mechanical sensitivity (ICC <0.3), offered good repeatability (ICC ≥0.7). The most reliable acclimatization protocol included five assessments over two weeks. MIA-related osteoarthritic change in pain was demonstrated with static weight-bearing, punctate tactile allodynia evaluation, treadmill exercise and operant PEAP, the latter being the most responsive to analgesic intra-articular lidocaine. Substance P and calcitonin gene-related peptide were higher in MIA groups compared to naive (adjusted P (adj-P) = 0.016) or sham-treated (adj-P = 0.029) rats. Repeated post-MIA lidocaine injection resulted in 34 times lower downregulation for spinal substance P compared to MIA alone (adj-P = 0.029), with a concomitant increase of 17 % in time spent on the PEAP dark side (indicative of increased comfort). This study of normal rats and rats with pain established the most reliable and sensitive pain assessment methods and an optimized acclimatization protocol. Operant PEAP testing was more responsive to lidocaine analgesia than other tests used, while neuropeptide spinal concentration is an objective quantification method attractive to support and validate different centralized pain functional assessment methods.

Osteoarthritis (OA) is a degenerative joint disease that is considered the primary source of chronic pain in cats, affecting well over a quarter of the feline population. Despite its prevalence, detection and diagnosis rates remain low, as many owners are unaware of the signs of feline OA. There is limited knowledge regarding the management of feline OA, with only 29 publications available, many of which lack rigorous methodology. Furthermore, most research focuses on the efficacy of non-steroidal anti-inflammatory drugs, while proposed alternatives to alleviate feline OA pain – such as food restriction, weight loss, adjunctive musculoskeletal treatments with biologics, physiotherapeutic modalities and lifestyle changes – are primarily based on human clinical studies and veterinary research on other species, which introduces a high risk of bias. New promising avenues are being explored with anti-nerve growth factor monoclonal antibodies; however, the long-term effects of repetitive administration, optimal conditions for administration and specific indications have yet to be described. Research from the Groupe de recherche en pharmacologie animale du Québec (GREPAQ) on pharmacological and non-pharmacological therapies for feline OA suggests that a shift in the OA management paradigm may be warranted. An omega-3 enriched diet has demonstrated therapeutic efficacy comparable to standard pharmacological treatments, without side effects and with high compliance. In addition, it was equally effective for cats with severe OA as for those with moderate OA. By establishing a theoretical framework for feline OA management based on robust scientific evidence, veterinarians will be better equipped to select treatments tailored to the diagnosed (or suspected) manifestations and mechanisms of OA pain, ultimately improving the health and well-being of their feline patients. Future research should explore the concomitant use of different therapeutic approaches, as they may offer superior outcomes compared with a single treatment through additive or synergistic effects.

Evaluation of nociceptive sensitisation in canine osteoarthritis studies has been poorly reported, or even related to other clinical symptoms. In 16 dogs, peak vertical force (PVF), subjective pain assessment using 3 scales, sympathetic stress response with electrodermal activity (EDA) measurement, and behavioural changes with video analysis and telemetered motor activity were quantified at baseline (D-7), and 28 and 56 days post transection of the cranial cruciate ligament. As markers of central sensitisation, selected spinal cord biomarkers (substance P and transthyretin) were quantified at D56. Electrical withdrawal thresholds on the stifle and the tail were measured as indicative of peripheral and central quantitative sensory testing (QST) sensitisation, respectively. The effects of vehicle administration (n=8) were compared with tiludronate (2mg/kg subcutaneously, q2 week, starting at D0) administration. Generalized estimated equations tested the association between the behavioural and physiological methods and QST sensitisation, and therefore the sensitivity of the methods for detecting treatment efficacy. Compared to tiludronate, at D56, vehicle-treated dogs had increased spinal substance P (P=0.01), concomitant decreased transthyretin (P=0.02), and (compared to baseline) demonstrated peripheral and central QST sensitisation, which was not present for tiludronate. Only PVF, the spontaneous behaviour "walking with full weight-bearing," and EDA were associated with occurrence of QST sensitisation and indicated significant tiludronate analgesic efficacy after inclusion of central QST sensitisation as a predictor variable in the statistical model. This study establishes the strong interest to implement QST as a predictor of canine osteoarthritis pain symptoms explained by pain sensitisation.

This study evaluated a therapeutic diet high in eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) of marine source (EPA:DHA ratio 0.69:1), turmeric extract, and hydrolysed collagen in cats (N = 30) with naturally occurring osteoarthritis (OA) over a 13-week (W) period, followed by a 4-W washout, using four previously validated pain/functional outcomes. Compared to the placebo diet, the therapeutic diet significantly improved peak vertical force (p = 0.017; W16, 64% responders), correlating to enhanced weight bearing; stair assay compliance (p < 0.001; W16, 87% responders), reflecting reduced fatigue related to OA pain; night-time actimetry (cohort effect; p = 0.05, 67% responders), suggesting greater spontaneous mobility and comfort; and MI-CAT(V) score (cohort effect; p < 0.001, 80% responders), indicating reduced functional impairments. The earliest therapeutic response was observed at W06, marked by an inflection point between actimetric linear regressions of both cohorts, confirmed by significant MI-CAT(V) differences (p < 0.007; W08; W12; W16). The MI-CAT(V) clinical metrology instrument was validated for inter-rater reliability, minimal placebo effect (<15% responders), and OA severity clustering. Despite baseline differences in biomechanical assessments (p < 0.05), both moderate and severe OA clusters responded equally positively to the therapeutic diet. Based on all outcomes, the therapeutic diet showed promise for the long-term management of feline OA, with no observed side effects.