A combination of different strategies, each targeting a different 'desensitizing' mechanism, might prove superior over monotherapies. Such combined therapy may include both bottom-up and top-down (e.g., opioids, combined μ-opioid receptor agonist and noradrenaline reuptake inhibitor drugs) strategies. Topically applied analgesic therapies have strong potential for (temporally) decreasing peripheral nociceptive input (bottom-up approach). Targeting metabolic (e.g., ketogenic diets) and neurotrophic factors (e.g., decreasing brain-derived neurotrophic factor) are promising new avenues for diminishing hyperexcitability of the CNS in central sensitization pain patients. Addressing conservative treatments, pain neuroscience education, cognitive behavioural therapy and exercise therapy are promising treatments for CS pain.

Expanded distribution of pain was correlated with some measures of CS in individuals with knee OA. Pain drawings may constitute an easy way for the early identification of CS in people with knee OA, but further research is needed.

Preoperative PNE combined with knee joint mobilization did not produce any additional benefits over time for knee pain and disability, and CS measures compared with biomedical education with knee joint mobilization. Superior effects in the PNE with knee joint mobilization group were only observed for psychosocial variables related to pain catastrophizing and kinesiophobia.