Dietary Supplementation with Palmitoyl-Glucosamine Co-Micronized with Curcumin Relieves Osteoarthritis Pain and Benefits Joint Mobility

SIMPLE SUMMARY: Canine osteoarthritis is a chronic degenerative joint disease and a major cause of elective euthanasia. The disorder increasingly limits joint motion, might cause lameness as well as pain, and impacts quality of life. An unmet need remains for safe and effective therapies for osteoarthritis. Palmitoyl-glucosamine and curcumin are used in animal nutrition. A co-micronized formulation, with the two substances being jointly processed to reduce their particle size and increase the extent to which they can be absorbed, is currently available on the European market. The present study investigated if this formulation could relieve joint pain and benefit mobility. Two well-established rat models of inflammation and osteoarthritis pain were used. Results from the first set of experiments showed that the dietary supplement relieved experimentally induced paw edema, infiltration of inflammatory cells, and decreased sensitivity to painful stimuli (thermal hyperalgesia). In the osteoarthritis model, the supplement proved to protect joint cartilage against degradation and successfully address neuropathic pain (i.e., pain from normally non-painful stimuli). Locomotor function recovered by 45% under supplement administration. The present findings suggest that the dietary supplement with palmitoyl-glucosamine co-micronized with curcumin might help manage osteoarthritis. ABSTRACT: Chronic mixed pain and orthopedic dysfunction are the most frequently associated consequences of canine osteoarthritis (OA). An unmet need remains for safe and effective therapies for OA. Palmitoyl-glucosamine (PGA) and curcumin are safe and naturally occurring compounds whose use is limited by poor bioavailability. Micronization is an established technique to increase bioavailability. The aim of this study was to investigate if the dietary supplementation with PGA co-micronized with curcumin (PGA-Cur, 2:1 ratio by mass) could limit pathologic process in two well-established rat models of inflammation and OA pain, i.e., subplantar carrageenan (CAR) and knee injection of sodium monoiodoacetate (MIA), respectively. In CAR-injected animals, a single dose of PGA-cur significantly reduced paw edema and hyperalgesia, as well as tissue damage and neutrophil infiltration. The repeated administration of PGA-Cur three times per week for 21 days, starting the third day after MIA injection resulted in a significant anti-allodynic effect. Protection against cartilage damage and recovery of locomotor function by 45% were also recorded. Finally, PGA-cur significantly counteracted MIA-induced increase in serum levels of TNF-α, IL-1β, NGF, as well as metalloproteases 1, 3, and 9. All the effects of PGA-Cur were superior compared to the compounds used singly. PGA-Cur emerged as a useful dietary intervention for OA.