Molecular Pathways Involved in Knee Pain

Sponsor
University of Nottingham
Study ID
NCT04443452
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
45 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Quantitative Sensory Testing — DIAGNOSTIC_TEST
    PPT: An electronic data collection unit will be used featuring an electronic algometer connected with a laptop where the amount of pressure will be displayed on the screen. When the pressure pain detection threshold is reached (the point where the pressure sensation starts to be experienced as pain), the individual will press a button at a handheld device, that will automatically store the pressure value in the system and serve as an indication, for the examiner, to stop the testing. TS: A pinprick stimulator (Weight: 256mNewton) will be used. The examiner will apply the pen that features a retractable blunt needle in a repetitive manner (once per second for ten seconds). The individual will be asked for the intensity of pain (NRS) at the first and at the last time and the given score will be noted. CPM: A manual blood pressure sphygmomanometer will be used in conjunction with the electronic algometer described above (PPT).
  • Radiographic Evaluation — RADIATION
    Tibiofemoral and patellofemoral radiographs of the most painful knee will be taken using a standardised protocol (standing posterior-anterior (PA) and skyline views) and will be scored by a single experienced observer in order to generate data for correlation analyses with the primary and secondary outcomes. A Perspex Rosenberg template with lead beads is used for the standing PA view to standardising the degree of knee flexion, foot rotation and magnification. PA radiographs are taken with the participant facing the x-ray tube while standing on the Rosenberg jig and leaning forwards with their thighs touching the anterior aspect of the jig, the x-ray beams passing from the posterior aspect through to the anterior aspect of the knee. Variable jigs are used for the skyline view to obtaining 300 of knee flexion with the participant lying in a reclined supine position on a couch. Grading of radiographs for changes of OA will be based on the Kellgren and Lawrence (K/L) score.
  • Ultrasound-guided Aspiration — PROCEDURE
    Ultrasound scanning will be conducted on the most painful knee to identify synovial effusion. During the ultrasound scan, the supra-patellar pouch, medial and lateral recess of the knees will be assessed for synovial thickening, synovial fluid/effusion and for positive power Doppler. An ultrasonic probe will be used to direct ultrasonic waves onto the knee joint during sonography, and a computer converts the signals received so that they can be presented on the screen. During skin application, a sterile probe cover and sterile acoustic gel will be used. Once the best aspiration location is identified and the location of the needle insertion marked, the skin will be prepared with a cleansing agent such as iodine or chlorhexidine. The needle may be introduced into the skin either parallel to the probe or perpendicular to the probe. Once the aspiration is completed, the needle will be removed, the skin cleansed, and a bandage will be applied.
  • Muscle Strength Assessment — DIAGNOSTIC_TEST
    Isometric testing will be done at 30 and 60 degrees of flexion as done in the previous study and the participant will be in sitting position with hips and knees strapped to keep the position standardised.
  • Function Assessment (A) — DIAGNOSTIC_TEST
    The participant will start in a seated position. The participant will stand up upon therapist's command, walk 3 meters, turn around, walk back to the chair and sit down. The time will stop when the participant is seated. The subject can use an assistive device. If the assistive device is used, it will be documented. Important Note: A practice trial will be completed before the timed trial.
  • Function Assessment (B) — DIAGNOSTIC_TEST
    The 30-Second Chair Test is administered using a chair. The participant is seated in the middle of the chair with arms crossed at the wrists and held against the chest. The participant will practice a repetition or 2 before completing the test. If a participant must use their arms to complete the test, they are scored 0. The participant is encouraged to complete as many full stands as possible within 30 seconds. The participant is instructed to fully sit between each stand. While monitoring the participant's performance to ensure proper form, the tester silently counts the completion of each correct stand. The score is the total number of stands within 30 seconds (more than halfway up at the end of 30 seconds counts as a full stand). Incorrectly executed stands are not counted. The 30-second chair stand involves recording the number of stands a person can complete in 30 seconds rather than the amount of time it takes to complete a pre-determined number of repetitions.
  • Balance Assessment — DIAGNOSTIC_TEST
    Static balance and postural sway either in the medial-lateral or antero-posterior direction will be assessed using the RS Scan force plate. The participant will be asked to stand on the plate looking straight forward for 30 seconds in two conditions: first with their eyes open and then with eyes closed. Medial-lateral, antero-posterior and total sway will be recorded.

Study Details

Knee osteoarthritis (OA) is the most common form of arthritis and the most common cause of knee pain in the world. The rate of knee arthritis is as high as that of cardiac disease and is the most common problem in individuals over the age of 65. Central Sensitization (CS) is a marker of widespread pain sensitivity that can occur throughout the central nervous system distribution, leading to changes in the spinal cord as well as in the brain. The presence of CS increases the complexity of the clinical picture and can negatively affect treatment outcomes. CS is present in \>20% of patients suffering from knee OA indicating that in the majority of individuals suffering with painful knee OA, knee pain should be related to molecular changes in the joint. CS might be also associated with discrete synovial fluid proteomic signatures due to the generation by the joint of chemical mediators (e.g. nerve growth factor) that drive CS, or CS might moderate the relationship between synovial fluid proteomic signatures and symptoms due to alterations in pain processing. The aim of this study is to explore the potential molecular links between pain and structure on knee pain using synovial fluid proteomics. A secondary purpose is to explore the association of knee pain with biomarkers of stress, metabolism and dietary habits. In a single session, ultrasound-guided synovial fluid, blood urine and saliva extraction, clinical assessment, completion of a questionnaire booklet and knee x-rays will be conducted. The clinical assessment will measure three features of central sensitisation (sensitivity to blunt pressure on the most painful knee, changes in pain felt during repeated light pricking of the knee skin, and reduction in pain that accompanies inflation of a blood pressure cuff on the non-dominant arm), features of leg strength (dynamometer, time up-and-go test) and features of balance (sway). Participant involvement at each session is expected to last less than 3 hours. Individuals over 45 having complaints of knee pain for 3-6 months are eligible to participate. The clinical assessments, questionnaire completion and subsequent statistical analysis are expected to be completed within 18 months of study commencement. The findings can provide more insight into the traits of knee pain, allow the examination of possible correlations to each other, and highlight potential detrimental effects of them on knee joint health.

Key Dates

Start date
Nov 6, 2020
Status verified
Apr 2025
Primary completion
Dec 1, 2023
Completion
Dec 1, 2023

Study Design

Enrollment
71 participants (actual)

Arms

  • Arm: Prevalent Central Sensitisation
    Participants with sensitisation that significantly deviates from the normal mean as assessed by Quantitative Sensory Testing
  • Arm: Non-prevalent Central Sensitisation
    All other participants with sensitisation that is not significantly deviating from the normal mean as assessed by Quantitative Sensory Testing

Primary Outcome Measure

Pain Sensitivity: Pressure Pain Detection Threshold (PPT) [ Time Frame: At baseline ]

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