Targeting Neuroinflammation in Osteoarthritis with Intra-Articular Adelmidrol

Abstract

Neuroinflammation is an emerging therapeutic target in chronic degenerative and autoimmune diseases, such as osteoarthritis (OA) and rheumatoid arthritis. Mast cells (MCs) play a key role in the homeostasis of joints and the activation of MCs induces the release of a huge number of mediators, which fuel the fire of neuroinflammation. Particularly, synovial MCs release substances which accelerate the degradation of the extra-cellular matrix causing morphological joint changes and cartilage damage and inducing the proliferation of synovial fibroblasts, angiogenesis, and the sprouting of sensory nerve fibers, which mediate chronic pain. Palmitoylethanolamide (PEA) is a well-known MCs modulator, but in osteoarthritic joints, its levels are significantly reduced. Adelmidrol, a synthetic derivate of azelaic acid belonging to the ALIAmides family, is a PEA enhancer. Preclinical and clinical investigations showed that the intra-articular administration of Adelmidrol significantly reduced MC infiltration, pro-inflammatory cytokine release, and cartilage degeneration. The combination of 1% high molecular weight hyaluronic acid and 2% Adelmidrol has been effectively used for knee osteoarthritis and, a significant improvement in analgesia and functionality has been recorded.

To Be Frail or Not to Be Frail: This Is the Question—A Critical Narrative Review of Frailty

“…Neuroinflammation is mediated by the release of pro-inflammatory cytokines by non-neuronal cells, such as astrocytes and microglia, which represents the innate immune system of the central nervous system. Neuroinflammation may also involve peripheral immune cells, like mast cells, which, when hyper-activated, may release many pro-inflammatory cytokines and immunomodulators, such as TNF-alpha, IL-6, IL-8, VEGF, histamine, heparin, and tryptase, which play a determinant role in the progression of osteoarthritis (OA) by promoting subcondral erosions, synoviocyte proliferation, angiogenesis, and pain sensitization [289]. Age and frailty are risk factors for the development of OA, which is a leading cause of chronic pain in the elderly [290].…”

Adelmidrol Protects Hyaluronic Acid against Oxidative Degradation and Improves the Outcome in Patients with Adhesive Capsulitis of the Shoulder Managed by Physical Therapy. In vitro Evidence and Two Case Reports

“…Recent evidence supports the in vivo antioxidant activity of ADM in animal models of colitis [30], ischemia/reperfusion injury [31] and pulmonary fibrosis [32], but the antioxidant protective effect has not yet been investigated at the molecular and cellular level. Recent preclinical and clinical studies have shed some light on the benefit of a new intra-articular formulation based on high molecular weight HA (1%) and ADM (2%) in osteoarthritis [33][34][35].…”

Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model

“…Considering that the cartilage is not innervated, OA pain is probably due to changes in the underlying bone and synovial inflammation [ 2 ]. Recent research revealed the crucial role of synovial inflammation in both OA incidence and progression and also in the genesis of pain [ 4 , 5 , 6 ]. Joint cells, such as synoviocytes, inflammatory cells (mast cells and macrophages), and chondrocytes, as well as infrapatellar fat pads that produce chemokines, cytokines, and proteases, which can initiate and maintain synovial inflammation, contribute to cartilage damage and sensitize primary afferent fiber terminals in adjacent tissues [ 6 , 7 , 8 , 9 ].…”