• Anthony Terrence O'Brien, Mirret M El-Hagrassy, Haley Rafferty, Paula Sanchez, Rodrigo Huerta, Swapnali Chaudhari, Sonia Conde, Gleysson Rosa, and Felipe Fregni.
• Department of Physical Medicine and Rehabilitation, Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Pain Med. 2019 May 1; 20 (5): 1000-1011.

ObjectiveTo study the impact of therapeutic interventions on pain analgesia and endogenous pain modulation in knee osteoarthritis (KOA).DesignSystematic review and meta-analysis.MethodsWe searched for KOA randomized clinical trials and observational studies with data on therapeutic interventions comparing pain intensity, temporal summation (TS), and conditioned pain modulation (CPM) scores relative to control. These data were pooled as Hedge's g. To study the relationship between pain intensity and TS/CPM, we performed metaregression with 10,000 Monte-Carlo permutations.ResultsWe reviewed 11 studies (559 participants). On studying all the interventions together, we found no significant changes in pain modulation, TS, or CPM. Our findings show that this lack of difference is likely because surgical and nonsurgical interventions resulted in contrary effects. Metaregression significantly correlated pain reduction with normalization of TS and CPM.ConclusionsWe demonstrate an association between pain reduction and TS/CPM normalization. Though we cannot directly compare these interventions, the results allow us to draw hypotheses on potential practice schemas. Recovering defective endogenous pain modulation mechanisms may help establish long-term analgesia. However, to validate these paradigms as robust clinical biomarkers, further investigation into their mechanisms would be necessary. The registration number for this review is CRD42017072066.© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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