Introduction: Musculoskeletal disorders have affected approximately 1.3 billion people worldwide. Evidence shows that chronic diseases and musculoskeletal conditions often occur together, and among them it is estimated that more than 240 million people worldwide have symptomatic osteoarthritis (OA) and activity limitation, which is a major contributor to chronic pain and changes central in pain processing. It is known that physical exercise (active approach to treatment) and manual therapy (passive approach) are capable of intervening in the pain processing system, but passive approaches have been little investigated. Among them, little is known about the effect of ischemic preconditioning (IPC) for pain management and its impact on conditioned pain modulation (CPM) and cardiac autonomic control. There is no evidence that IPC causes systemic hypoalgesia and increased vagal modulation, so this provides a rationale for study. Objectives: To analyze the acute effect of IPC on local pain, CPM and cardiac autonomic control in women with knee OA and observe whether there is a correlation between them. Methods: Double-blind, placebo-controlled, randomized clinical trial. Participants will be divided into IPC or placebo groups. Outcomes evaluated: CPM and cardiac autonomic modulation. Comparisons will be performed using Generalized Mixed Linear Models fitted to the data. For correlation, the Pearson or Spearman correlation test will be used according to the normality of the data. All analyzes will assume a significance level of p<0.05.

Inclusion Criteria:

• Medical diagnosis for uni or bilateral OA of the tibiofemoral joint (grade II or superior Kellgren-Lawrence radiographic changes);
• Not having systemic rheumatic diseases such as fibromyalgia, rheumatoid arthritis, systemic lupus erythematosus;
• Not having total knee arthroplasty, knee ligament injury, history of knee surgery;
• Not having heart disease, congestive heart failure, or a history of acute myocardial infarction (except those with hypertension);
• Not having diagnosis of neurological, metabolic, endocrine disorder, respiratory disease;
• Not being an alcoholic or smoker;
• Not use drugs that influence cardiac autonomic modulation (beta-blocker);
• Not having one or more predisposing risk factors for thromboembolism.

Exclusion Criteria:

• Use anti-inflammatory drugs or analgesics 24 hours before the test;
• Perform physical activity;
• Consume alcohol;
• Perform therapeutic treatments for pain relief;
• Errors in capturing the RR intervals;
• Want to leave the study.

Women with knee OA, aged 45 years or less and younger than 80 years.

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