In the last few years, neuroinflammation has been identified as a promising therapeutic target in chronic degenerative diseases, such as osteoarthritis (OA) and rheumatoid arthritis. In the healthy joint, synovial tissue macrophages (STM) or mast cells (MCs) represent nearly 3% of cellular population of the synovia and act as sentinels. However, in chronically inflamed joints, their density significantly increases and their activation induces the release of a huge number of mediators, which may accelerate the degradation of the extra-cellular matrix causing morphological joint changes and cartilage damage. Hyperactivated MCs may induce the proliferation of synovial fibroblasts, angiogenesis and the sprouting of sensory nerve fibers, which mediate chronic pain. Moreover, MCs may influence the hyaluronic acid (HA) metabolism, through two mechanisms of action: firstly, MCs release tryptases, which may accelerate HA destruction; secondly, MCs contain heparin, which represents the preliminary stage in the synthesis of HA.

Palmitoylethanolamide (PEA) is a well-known MCs modulator, which may restore MCs in their physiological function; however, it has been shown to be significantly reduced in osteoarthritic joints.

Adelmidrol is a synthetic derivate of azelaic acid belonging to the ALIAmides family, which works as a PEA enhancer. Preclinical studies showed that intra-articular administration of Adelmidrol significantly reduced MCs infiltration, proinflammatory cytokines release and cartilage degeneration.

A new combination of 1% high molecular weight hyaluronic acid and 2% Adelmidrol has been recently introduced in the market. Clinical trials showed its efficacy and safety in patients suffering from Kellgren and Lawrence grade II-III osteoarthritis of the knee. After 4 weekly intra-articular injections patients reported a significant improvement of analgesia and functionality, as measured in the WOMAC scale. These results were maintained during the two-year follow-up study.

Flaminia Coluzzi completed her residency in anesthesia and intensive care at the same university. In March 2008, she began working at the Sapienza University of Rome as a Research Associate Professor. She has been studying acute and chronic pain management for about 20 years. Her research is focused on the role of opioids and adjuvants in chronic non-malignant and cancer pain, endocrine effects of analgesics, emerging techniques in post-operative pain management, new molecular targets for osteoarthritis and metastatic bone disease, and chronic pain management in vulnerable patients. She has 135 publications on Scopus that have been cited 2688 times, and her publication h index is 30. He has been serving as an editorial board member of several reputed journals.