Effects of Ischemic Preconditioning on Conditioned Pain Modulation and Heart Rate Variability in Knee Osteoarthritis

Effects of Ischemic Preconditioning on Conditioned Pain Modulation and Heart Rate Variability in Women With Knee Osteoarthritis: Placebo-Controlled Randomized Clinical Trial

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Preconditioning
• Intervention / Treatment: Device: Ischemic Preconditioning

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Presidente Prudente, SP, Brazil, 55
      • Franciele Marques Vanderlei

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ischemic Preconditioning (n= 22); The IPC protocol will be applied in the proximal region of the thigh of the limb with knee osteoarthritis and if both knees are affected, it will be applied to the knee with the greatest complaint of pain. Participants will be relaxed and comfortably seated. The same cuff used to determine the total occlusion pressure (TOP) will be used and the protocol will consist of four cycles of total ischemia (according to the TOP value determined individually) of five minutes, followed immediately by four cycles of five minutes of vascular reperfusion (0 mmHg ), totaling 40 minutes.	Device: Ischemic Preconditioning; The Ischemic Preconditioning (IPC) is characterized by the application of brief periods of circulatory occlusion (ischemia) and reperfusion of a limb in the minutes to hours that precede the exercise through the insufflations and deflations of a pressure cuff.
Placebo Comparator: Placebo (n= 22); The placebo protocol will be performed on the lower limb with knee osteoarthritis and if both knees are affected, it will be applied to the knee with the greatest complaint of pain. Participants will perform a protocol similar to the IPC, but during the four cycles of five minutes of occlusion, the cuffs will only be inflated with 10mmHg so as not to cause arterial or venous occlusion, alternating with four cycles of five minutes of reperfusion (0 mmHg).	Device: Ischemic Preconditioning; The Ischemic Preconditioning (IPC) is characterized by the application of brief periods of circulatory occlusion (ischemia) and reperfusion of a limb in the minutes to hours that precede the exercise through the insufflations and deflations of a pressure cuff.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conditioned Pain Modulation	Conditioned pain modulation is a dynamic measure capable of evaluating endogenous pain inhibition using a "pain-by-pain inhibition" model in which pain in a local area (test stimulus) is inhibited by a second concomitant pain (pain stimulus) conditioning). In this study, the test stimulus will be performed through the pressure pain threshold using algometer and the conditioning stimulus will be performed by immersing the hand in cold water, using the cold pressor test - CPT.	Change from baseline after intervention.
Cardiac Autonomic Modulation	The assessment of cardiac autonomic modulation will be performed using HRV through the capture of heart rate beat to beat (RR intervals) using a heart rate monitor (Polar Electro Oy, Kempele, Finland - model V800) which is a validated equipment.	Change from baseline after intervention.

Collaborators and Investigators

• Sponsor: Paulista University

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2023
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): December 15, 2024

Study Registration Dates

• First Submitted: August 30, 2021
• First Submitted That Met QC Criteria: September 20, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): May 31, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: chronic pain; osteoarthritis; autonomic nervous system; ischemic preconditioning; heart rate variability; therapeutic occlusion; conditioned pain modulation
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Pathologic Processes; Arthritis; Joint Diseases; Rheumatic Diseases; Ischemia; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 5543/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No