Pain, Chronic PostsurgicalNCT05575310
Central Sensitization in Total Knee Arthroplasty Patients with Persistent Pain
An observational study of Pain, Chronic Postsurgical and Knee Osteoarthritis, run by University of Barcelona at 1 site in Spain.
Trial summary
Persistent post-surgical pain is a significant adverse effect after total knee arthroplasty, present in around 20% of the patients. Central sensitization may contribute to developing and maintaining pain. Therefore studies should investigate if pain processing altered mechanisms are present in this population. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Chronic Postsurgical, Knee Osteoarthritis, Sensitization, Central
- What is being tested?
- Total Knee Arthroplasty
- Type of treatment
- Surgery or procedure
- How many people
- 117 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jan 2023to 22 Oct 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Subjects who underwent total knee arthroplasty due to symptomatic, end-stage knee ostheoarthritis.
Who may be able to join
- Patients who underwent total knee arthroplasty due to painful primary osteoarthritis.
Who cannot join
- Patients operated due to a revision surgery.
- Patients with a unicompartmental knee arthroplasty
- Pateints operated due to a fracture.
- Patients planning to undergo another lower extremity operation during the following 12 months.
- Patients with inflammatory or rheumatic diseases such as: rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus or ankylosing spondylitis.
- Patients with mental health conditions and/or major depression.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Central Sesitization in Patients with Persistent Postsurgical Pain After a Knee Arthroplasty: a Prospective, Case Control, Observational Study
Persistent post-surgical pain is a significant adverse effect after total knee arthroplasty, present in around 20% of the patients. Central sensitization may contribute to developing and maintaining pain. Therefore studies should investigate if pain processing altered mechanisms are present in this population.
Read the detailed description
Numerous studies suggest that peripheral and central sensitization in patients with symptomatic knee osteoarthritis could be an important factor capable of explaining part of these poor outcomes after knee arthroplasty. Quantitative sensory testing has been frequently used to investigate this sensitization of the central nervous system and assess pain hypersensitivity locally and away from the affected region in patients with chronic knee osteoarthritis pain. Pressure algometry is a method described to determine pain thresholds to pressure and thus evaluate the sensitivity to pain due to tissue pressure. However, another aspect associated with sensitization is the downward modulation of peripheral inputs. This occurs in neurons in the posterior horn of the medulla and can be either inhibitory or facilitatory. The conditioned pain modulation test is a manifestation of this phenomenon, which can be easily assessed in patients, and is characterized by the modification of the response to the application of a painful stimulus when a second conditioning painful stimulus is applied. Conditioned pain modulation has been shown to be altered in patients with symptomatic knee osteoarthritis.
The literature suggests that although one of the main components of pain perpetuation with people with knee osteoarthritis is sensitization of the nervous system, successful knee arthroplasty is able to normalize its functioning. This implies that the maintenance of sensitization can be triggered by peripheral nociceptive stimuli. When performing a knee arthroplasty, the structures capable of generating these peripheral nociceptive stimuli are eliminated, so that the pain-generating mechanisms cannot be the same as before in those who manifest persistent post-surgical pain. For this reason, one of the hypotheses is that the mechanism responsible for causing this pain is a central mechanism and not a peripheral one. Although this hypothesis has not been fully tested, there are indications that people with chronic post-surgical pain may suffer peripheral and central sensitization processes, very similar to those that can be observed in people with symptomatic osteoarthritis of the knee that is not operated on, even though the structures involved are no longer present. This fact reinforces the theory of the involvement of a central mechanism in the perpetuation of pain after surgery.
Therefore, the present study aims to investigate the involvement of the central sensitization process in the perpetuation of postoperative pain in individuals undergoing total knee arthroplasty for primary symptomatic knee osteoarthritis. From a clinical point of view, current postoperative treatments focus mainly on improving the patient's functional outcomes (e.g., physical function and joint range of motion), and the status of the descending pain modulator system is rarely taken into account. The present study seeks to place importance on the central mechanisms in the perpetuation of pain after knee arthroplasty, to inspire new treatment protocols that take these processes into account.
- Being tested
- Total Knee Arthroplasty
- Medical subject headings
- Pain, Postoperative, Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total Knee ArthroplastyProcedure or surgery
Articular knee surface replacement
| Study group | Role | What they receive |
|---|---|---|
| No Persistent Post Surgical Pain | The grouping variable will be the presence or not of persistent post-surgical pain. This will be a dichotomous variable obtained from the evaluation of pain intensity at 3 months after surgery. The tool used will be a 100mm Visual Analog Scale (VAS) (0 = no pain, 100 = worst pain imaginable) (25). Those with a VAS < 30 will be considered as patients with no persistent pain, while those with a VAS ≥ 30 will be considered as patients with persistent pain. This cut-off point has been determined by numerous authors in previous studies. Receives: Procedure: Total Knee Arthroplasty | |
| Persistent Post Surgical Pain | While those with a VAS ≥ 30 will be considered as patients with persistent pain. This cut-off point has been determined by numerous authors in previous studies Receives: Procedure: Total Knee Arthroplasty |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conditioned Pain Modulation at 3 months
Experimental tonic pain will be induced by immersing the hand against the side in cold water following the Cold Pressor Test protocol (CPT). CPT will be performed by holding the contralateral hand immersed in water at 12±1 °C up to the wrist for a period of 2 minutes. The evaluation of pain thresholds to pressure will be performed after 45 seconds of immersion at location 1 of the peripatellar region (bilateral) and to the dominant forearm. Both evaluation points have been described in the section on pressure pain thresholds.
The final value corresponding to the conditioned modulation of pain will be obtained from the difference between the value obtained during the application of the conditioning stimulus and the previous value. The unit of measurement will be in kilopascals (kPa) (conditioned pain modulation = pain threshold at pressure during application of cold - pain threshold at pressure before application of cold).
Measured: 3 months after surgery
Conditioned Pain Modulation at 6 months
Experimental tonic pain will be induced by immersing the hand against the side in cold water following the Cold Pressor Test protocol (CPT). CPT will be performed by holding the contralateral hand immersed in water at 12±1 °C up to the wrist for a period of 2 minutes. The evaluation of pain thresholds to pressure will be performed after 45 seconds of immersion at location 1 of the peripatellar region (bilateral) and to the dominant forearm. Both evaluation points have been described in the section on pressure pain thresholds.
The final value corresponding to the conditioned modulation of pain will be obtained from the difference between the value obtained during the application of the conditioning stimulus and the previous value. The unit of measurement will be in kilopascals (kPa) (conditioned pain modulation = pain threshold at pressure during application of cold - pain threshold at pressure before application of cold).
Measured: 6 months after surgery
Secondary outcomes (3)
Pressure Pain Threshold
Eight test sites in the peripatellar region, one control site on tibialis anterior (5 cm distal to the tibial tuberosity) and one control site on the extensor carpi radialis longus (5 cm distal to lateral epicondyle of humerus) were located and marked. The eight sites were located in relation to bone landmark. Site 1: 2 cm distal to the inferior medial edge of patella; site 2: 2 cm distal to the inferior lateral edge of patella; site 3: 3 cm lateral to the mid point on the lateral edge of patella; site 4: 2 cm proximal to the superior lateral edge of patella; site 5: 2 cm proximal to the superior edge of patella; site 6: 2 cm proximal to the superior medial edge of patella; site 7: 3 cm medial to the mid point on the medial edge of patella; site 8: at centre of patella. A hand-held pressure algometer (PAIN TEST™ FPX 50) was used for measuring PPT.
Measured: 3 and 6 months after surgery
Health Functioning
The Spanish version of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used as a measure of health functioning after KA. The WOMAC is a multidimensional scale composed of 24 items grouped into three dimensions: pain (five items), stiffness (two items) and physical function (seventeen items). The WOMAC uses a 5-point Likert scale with responses ranging from 0 - none to 4 - extreme. The final score for the WOMAC was determined by summing the aggregate scores for pain, stiffness, and physical function. The WOMAC is valid and reliable for assessing health functioning in OA participants and is sensitive to changes in health functioning in those who underwent KA.
Measured: 3 and 6 months after surgery
Pain intensity
Pain will be assessed using the reduced version of the McGill Pain Questionnaire (SF-MPQ). The SF*MPQ is a self-administered questionnaire composed of 15 descriptors, 11 of which describe sensory aspects of pain and 4 describe aspects concerning the affective dimension of pain. Each pain descriptor is assessed by scores ranging from 0 to 3 (none, mild, moderate and severe). The pain score is calculated from the sum of the values of the intensity range chosen for each descriptor. The SF-MPQ is considered a valid and reliable assessment tool, routinely used during clinical practice.
Measured: 3 and 6 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2022
- Study start1 Jan 2023
- Primary completion22 Oct 2024
- Study completion22 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pain, Chronic PostsurgicalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Barcelona
- Sponsor type
- University, hospital or other
- Collaborators
- Consorci Hospitalari de Vic, University of Vic - Central University of Catalonia
- Responsible party
- Principal investigator, Marc Terradas Monllor, University of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05575310
- Sponsor's protocol ID
- CS-TKA
- Status last verified
- Oct 2024
- First submitted
- 17 Sep 2022
- Last updated
- 24 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Terradas-Monllor M, Ullastre-Pujal M, Dausteler C, Roca-Ribera R, Roca-Esteban A, Garcia Del Sol C, Cuesta-Casas M, Minobes-Molina E, Terre-Boliart R, Pares-Martinez C, Ochandorena-Acha M. Impaired Conditioned Pain Modulation and Peripheral Sensitization in Chronic Postsurgical Pain After Total Knee Arthroplasty. Clin J Pain. 2026 Jul 1;42(7):e1387. doi: 10.1097/AJP.0000000000001387.
PubMed 41914560
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Central Sesitization in Patients with Persistent Postsurgical Pain After a Knee Arthroplasty: a Prospective, Case Control, Observational Study
- ClinicalTrials.gov ID
- NCT05575310
- Acronym / sponsor ID
- CS-TKA
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- University of BarcelonaUniversity, hospital or other
- Collaborators
- Consorci Hospitalari de Vic, University of Vic - Central University of Catalonia
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 22 Oct 2024 (actual)
- Study completion
- 22 Oct 2024 (actual)
- First posted
- 12 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Persistent post-surgical pain is a significant adverse effect after total knee arthroplasty, present in around 20% of the patients. Central sensitization may contribute to developing and maintaining pain. Therefore studies should investigate if pain processing altered mechanisms are present in this population.
Detailed description
Numerous studies suggest that peripheral and central sensitization in patients with symptomatic knee osteoarthritis could be an important factor capable of explaining part of these poor outcomes after knee arthroplasty. Quantitative sensory testing has been frequently used to investigate this sensitization of the central nervous system and assess pain hypersensitivity locally and away from the affected region in patients with chronic knee osteoarthritis pain. Pressure algometry is a method described to determine pain thresholds to pressure and thus evaluate the sensitivity to pain due to tissue pressure. However, another aspect associated with sensitization is the downward modulation of peripheral inputs. This occurs in neurons in the posterior horn of the medulla and can be either inhibitory or facilitatory. The conditioned pain modulation test is a manifestation of this phenomenon, which can be easily assessed in patients, and is characterized by the modification of the response to the application of a painful stimulus when a second conditioning painful stimulus is applied. Conditioned pain modulation has been shown to be altered in patients with symptomatic knee osteoarthritis.
The literature suggests that although one of the main components of pain perpetuation with people with knee osteoarthritis is sensitization of the nervous system, successful knee arthroplasty is able to normalize its functioning. This implies that the maintenance of sensitization can be triggered by peripheral nociceptive stimuli. When performing a knee arthroplasty, the structures capable of generating these peripheral nociceptive stimuli are eliminated, so that the pain-generating mechanisms cannot be the same as before in those who manifest persistent post-surgical pain. For this reason, one of the hypotheses is that the mechanism responsible for causing this pain is a central mechanism and not a peripheral one. Although this hypothesis has not been fully tested, there are indications that people with chronic post-surgical pain may suffer peripheral and central sensitization processes, very similar to those that can be observed in people with symptomatic osteoarthritis of the knee that is not operated on, even though the structures involved are no longer present. This fact reinforces the theory of the involvement of a central mechanism in the perpetuation of pain after surgery.
Therefore, the present study aims to investigate the involvement of the central sensitization process in the perpetuation of postoperative pain in individuals undergoing total knee arthroplasty for primary symptomatic knee osteoarthritis. From a clinical point of view, current postoperative treatments focus mainly on improving the patient's functional outcomes (e.g., physical function and joint range of motion), and the status of the descending pain modulator system is rarely taken into account. The present study seeks to place importance on the central mechanisms in the perpetuation of pain after knee arthroplasty, to inspire new treatment protocols that take these processes into account.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No Persistent Post Surgical Pain | – | Procedure: Total Knee ArthroplastyThe grouping variable will be the presence or not of persistent post-surgical pain. This will be a dichotomous variable obtained from the evaluation of pain intensity at 3 months after surgery. The tool used will be a 100mm Visual Analog Scale (VAS) (0 = no pain, 100 = worst pain imaginable) (25). Those with a VAS < 30 will be considered as patients with no persistent pain, while those with a VAS ≥ 30 will be considered as patients with persistent pain. This cut-off point has been determined by numerous authors in previous studies. |
| Persistent Post Surgical Pain | – | Procedure: Total Knee ArthroplastyWhile those with a VAS ≥ 30 will be considered as patients with persistent pain. This cut-off point has been determined by numerous authors in previous studies |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects who underwent total knee arthroplasty due to symptomatic, end-stage knee ostheoarthritis.
Key inclusion criteria (1 listed)
- Patients who underwent total knee arthroplasty due to painful primary osteoarthritis.
Key exclusion criteria (6 listed)
- Patients operated due to a revision surgery.
- Patients with a unicompartmental knee arthroplasty
- Pateints operated due to a fracture.
- Patients planning to undergo another lower extremity operation during the following 12 months.
- Patients with inflammatory or rheumatic diseases such as: rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus or ankylosing spondylitis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Total Knee ArthroplastyArticular knee surface replacement | Procedure or surgery | No Persistent Post Surgical Pain, Persistent Post Surgical Pain |
Primary outcome
Conditioned Pain Modulation at 3 months
Time frame: 3 months after surgery
Experimental tonic pain will be induced by immersing the hand against the side in cold water following the Cold Pressor Test protocol (CPT). CPT will be performed by holding the contralateral hand immersed in water at 12±1 °C up to the wrist for a period of 2 minutes. The evaluation of pain thresholds to pressure will be performed after 45 seconds of immersion at location 1 of the peripatellar region (bilateral) and to the dominant forearm. Both evaluation points have been described in the section on pressure pain thresholds. The final value corresponding to the conditioned modulation of pain will be obtained from the difference between the value obtained during the application of the conditioning stimulus and the previous value. The unit of measurement will be in kilopascals (kPa) (conditioned pain modulation = pain threshold at pressure during application of cold - pain threshold at pressure before application of cold).
Conditioned Pain Modulation at 6 months
Time frame: 6 months after surgery
Experimental tonic pain will be induced by immersing the hand against the side in cold water following the Cold Pressor Test protocol (CPT). CPT will be performed by holding the contralateral hand immersed in water at 12±1 °C up to the wrist for a period of 2 minutes. The evaluation of pain thresholds to pressure will be performed after 45 seconds of immersion at location 1 of the peripatellar region (bilateral) and to the dominant forearm. Both evaluation points have been described in the section on pressure pain thresholds. The final value corresponding to the conditioned modulation of pain will be obtained from the difference between the value obtained during the application of the conditioning stimulus and the previous value. The unit of measurement will be in kilopascals (kPa) (conditioned pain modulation = pain threshold at pressure during application of cold - pain threshold at pressure before application of cold).
3 secondary outcomes
Pressure Pain Threshold
Time frame: 3 and 6 months after surgery
Health Functioning
Time frame: 3 and 6 months after surgery
Pain intensity
Time frame: 3 and 6 months after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2024.
- Derived from this study: PubMed 41914560Terradas-Monllor M, Ullastre-Pujal M, Dausteler C, Roca-Ribera R, Roca-Esteban A, Garcia Del Sol C, Cuesta-Casas M, Minobes-Molina E, Terre-Boliart R, Pares-Martinez C, Ochandorena-Acha M. Impaired Conditioned Pain Modulation and Peripheral Sensitization in Chronic Postsurgical Pain After Total Knee Arthroplasty. Clin J Pain. 2026 Jul 1;42(7):e1387. doi: 10.1097/AJP.0000000000001387.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pain, Chronic Postsurgical and Knee Osteoarthritis, run by University of Barcelona at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conditioned Pain Modulation at 3 months (time frame: 3 months after surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05575310, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2024.