The Enemy from Within: Systemic Influences Driving OA

The pain intensity experienced by patients with chronic musculoskeletal pain has often no relation to the status of the joint eg. minimal joint damage or inflammation may cause severe pain whereas severe joint degeneration or inflammation can cause minimal pain. A variety of factors may explain this disconnects including eg. psychological factors, sleep quality, pain peripheral or central sensitisation, genetic factors, and most recently epigenetic factors. 

In recent years quantitative, pain assessment tools (pain biomarkers) have been applied to provide advanced mechanistic profiling of patients with painful osteoarthrosis for 1) better diagnosis, 2) profiling effect of pharmacological and non-pharmacological treatment, and 3) for predicting pain trajectories and outcome after eg. surgery. A mechanistic pain profiling approach may pave the way for developing better and more targeted personalized pain management approaches for eg. osteoarthritis and for preventing chronic pain outcomes after surgery. 

An innovative pain profiling platform includes quantitative sensory tests as well as serological markers (proteomics and epigenetics). The most recent developments have been in the field of epigenetics where we have found that microRNA and small non-coding RNA may regulate several pathways, including pain/inflammation and found to be important markers for the pain development trajectories in patients with osteoarthritis.

Seventy-five years ago, Hench, Kendall, and colleagues administered synthesized cortisol to patients with arthritis, achieving unprecedented pain relief. However, the emergence of side effects, including on the musculoskeletal system, prompted intense scientific investigation into the molecular mechanisms of steroid action. While it is well established that glucocorticoids primarily act through nuclear receptors—ligand-induced transcription factors that regulate gene expression—recent studies have uncovered that glucocorticoids also modulate inflammatory cell metabolism through non-genomic pathways. This additional mechanism offers promising avenues for developing novel anti-inflammatory therapies, potentially improving the management of complex diseases such as arthritis.