Trial Outcomes & Findings for Persistent Postoperative Pain and Joint Stiffness After Total Knee Arthroplasty Performed for Osteoarthritis (NCT NCT02626533)

NCT ID: NCT02626533

Last Updated: 2024-12-27

Results Overview

Defined as numeric rating scale (NRS) pain score ≥4 with activity in the operated joint. A lower score is a better outcome. 0 is no pain, and 10 is worst pain imaginable.

• Recruitment status: COMPLETED
• Target enrollment: 179 participants
• Primary outcome timeframe: 6 months after date of surgery
• Results posted on: 2024-12-27

Participant Flow

Participant milestones

Measure	Total Knee Arthroplasty Patients Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.
Overall Study STARTED	179
Overall Study POD 1 Follow up	162
Overall Study POD 2 Follow up	162
Overall Study 4 Weeks Post-op	162
Overall Study 6 Weeks Post-op	162
Overall Study 3 Month Post-op	162
Overall Study 6 Months Post-op	162
Overall Study Stratified to "Stiff" Group	32
Overall Study Stratified to "Non-stiff" Group	130
Overall Study COMPLETED	162
Overall Study NOT COMPLETED	17

Reasons for withdrawal

Measure	Total Knee Arthroplasty Patients Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.
Overall Study Protocol Violation	14
Overall Study Patients were found have meet criteria under the exclusion criterion	2
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Persistent Postoperative Pain and Joint Stiffness After Total Knee Arthroplasty Performed for Osteoarthritis

Baseline characteristics by cohort

Measure	Total Knee Arthroplasty Patients (Stiff) n=32 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).	Total Knee Arthroplasty Patients (Non-Stiff) n=130 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).	Total n=162 Participants Total of all reporting groups
Age, Continuous	65.8 years STANDARD_DEVIATION 8.9 • n=5 Participants	67.3 years STANDARD_DEVIATION 7.9 • n=7 Participants	66.9 years STANDARD_DEVIATION 8.2 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	75 Participants n=7 Participants	92 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	55 Participants n=7 Participants	70 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants	11 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized White	26 Participants n=5 Participants	116 Participants n=7 Participants	142 Participants n=5 Participants
Race/Ethnicity, Customized Declined/Unknown	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months after date of surgery

Population: Some patients lost to follow up

Defined as numeric rating scale (NRS) pain score ≥4 with activity in the operated joint. A lower score is a better outcome. 0 is no pain, and 10 is worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=111 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Presence of Persistent Postoperative Pain Using the Numeric Rating Scale (NRS)	10 Participants	—

SECONDARY outcome

Timeframe: 6 weeks after date of surgery

The number of patients that experienced postoperative joint stiffness, defined as ≤95 degrees range of motion.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=162 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Patients Who Experienced Postoperative Joint Stiffness	32 Participants	—

SECONDARY outcome

Timeframe: 6 weeks after date of surgery

Population: some patients did not answer the questionnaire

Range of motion at 6 weeks postoperative. Measured as flexion minus extension. Measured in degrees.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=32 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=130 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Postoperative Knee Range of Motion	84 degrees Standard Deviation 15.6	115.3 degrees Standard Deviation 8.5

SECONDARY outcome

Timeframe: 1 day after surgery

Population: some lost to follow up

NRS pain at rest on postoperative day 1, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=15 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=145 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
NRS Pain at Rest on POD1	4.9 units on a scale Standard Deviation 3.6	3.2 units on a scale Standard Deviation 2.5

SECONDARY outcome

Timeframe: 1 day after surgery

Population: Some patients lost to follow up or did not answer questionnaire.

NRS pain with movement on postoperative day 1, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=13 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=139 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
NRS Pain With Movement on POD1	7.6 units on a scale Standard Deviation 2.8	4.9 units on a scale Standard Deviation 2.7

SECONDARY outcome

Timeframe: 1 day after surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Worst NRS pain on postoperative day 1, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=15 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=145 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Worst NRS Pain on POD1	7.7 score on a scale Standard Deviation 2.6	6 score on a scale Standard Deviation 2.7

SECONDARY outcome

Timeframe: 1 day after surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Least numerical rating scale (NRS) pain on postoperative day 1, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=15 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=145 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Least NRS Pain on POD1	1.5 units on a scale Standard Deviation 2.3	1.2 units on a scale Standard Deviation 1.7

SECONDARY outcome

Timeframe: 2 days after surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Numerical rating scale (NRS) pain at rest on postoperative day 2, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=14 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=137 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
NRS Pain at Rest on POD2	5.3 score on a scale Standard Deviation 3	3.2 score on a scale Standard Deviation 2.2

SECONDARY outcome

Timeframe: 2 days after surgery

Numerical rating scale (NRS) pain with movement on postoperative day 2, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=14 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=137 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
NRS Pain With Movement on POD2	7.4 score on a scale Standard Deviation 2.1	6.2 score on a scale Standard Deviation 2.2

SECONDARY outcome

Timeframe: 2 days after surgery

Worst numerical rating scale (NRS) pain on postoperative day 2, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=14 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=137 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Worst NRS Pain on POD2	9.1 score on a scale Standard Deviation 1.4	7.7 score on a scale Standard Deviation 2

SECONDARY outcome

Timeframe: 2 days after surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Least numerical rating scale (NRS) pain on postoperative day 2, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=14 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=137 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Least NRS Pain on POD2	3.1 score on a scale Standard Deviation 2.4	1.8 score on a scale Standard Deviation 2

SECONDARY outcome

Timeframe: 4 weeks after surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Numerical rating scale (NRS) pain at rest on 4 weeks postoperative, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=14 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=126 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
NRS Pain at Rest 4 Weeks After Surgery	2.9 score on a scale Standard Deviation 2.3	2 score on a scale Standard Deviation 1.7

SECONDARY outcome

Timeframe: 4 weeks after surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Numerical rating scale (NRS) pain with movement on 4 weeks postoperative, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=14 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=126 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
NRS Pain With Movement 4 Weeks After Surgery	4.3 score on a scale Standard Deviation 2.9	3.3 score on a scale Standard Deviation 2.2

SECONDARY outcome

Timeframe: 4 weeks after surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Worst numerical rating scale (NRS) pain 4 weeks postoperative, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=14 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=126 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Worst NRS Pain 4 Weeks After Surgery	5.9 score on a scale Standard Deviation 2.2	5.4 score on a scale Standard Deviation 2.3

SECONDARY outcome

Timeframe: 4 weeks after surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Least numerical rating scale (NRS) pain 4 weeks postoperative, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=14 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=126 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Least NRS Pain 4 Weeks After Surgery	1.5 score on a scale Standard Deviation 1.6	0.8 score on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: 3 months after surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Numerical rating scale (NRS) pain at rest 3 months postoperative, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=11 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=109 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
NRS Pain at Rest 3 Months After Surgery	2.4 score on a scale Standard Deviation 2.8	0.8 score on a scale Standard Deviation 1.5

SECONDARY outcome

Timeframe: 3 months after surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Numerical rating scale (NRS) pain with movement 3 months postoperative, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

The average NRS pain for all participants who completed the survey at 3 months is reported.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=11 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=109 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
NRS Pain With Movement 3 Months After Surgery	3.4 score on a scale Standard Deviation 2.7	1.5 score on a scale Standard Deviation 1.9

SECONDARY outcome

Timeframe: 3 months after date of surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Worst numerical rating scale (NRS) pain 3 months postoperative, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

The average worst NRS pain for all participants who completed the survey at 3 months is reported.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=11 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=109 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Worst NRS Pain 3 Months After Surgery	4.1 score on a scale Standard Deviation 2.5	2.3 score on a scale Standard Deviation 2.2

SECONDARY outcome

Timeframe: 3 months after date of surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Least numerical pain rating (NRS) pain 3 months postoperative, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

The average least NRS pain for all participants who completed the survey at 3 months is reported.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=11 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=109 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Least NRS Pain 3 Months After Surgery	0.8 score on a scale Standard Deviation 1.3	0.3 score on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: 6 months after date of surgery

Population: Some patients lost to follow up or did not answer questionnaire.

NRS pain at rest 6 months postoperative, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

The average NRS pain at rest for all participants who completed the survey at 6 months is reported.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=14 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=145 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
NRS Pain at Rest 6 Months After Surgery	2.4 score on a scale Standard Deviation 2.4	0.4 score on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: 6 months after date of surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Least NRS pain 6 months postoperative, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

The average least NRS pain for all participants who completed the survey at 6 months is reported.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=14 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=145 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Least NRS Pain 6 Months After Surgery	0.7 score on a scale Standard Deviation 1.3	0.1 score on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: 6 months after date of surgery

Population: Some patients lost to follow up or did not answer questionnaire.

Least NRS pain 6 months postoperative, measured from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

The average worst NRS pain for all participants who completed the survey at 6 months is reported.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=14 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=145 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Worst NRS Pain 6 Months After Surgery	6.5 score on a scale Standard Deviation 2.4	1.4 score on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: 4 weeks, 3 months, and 6 months after date of surgery

Population: This outcome was measured at three different timepoints (4 weeks, 3 months, and 6 months). Some participants could not be reached for follow-up at certain timepoints, therefore the number of patients analyzed for each timepoint differs.

The Knee Injury and Osteoarthritis Outcome Score (KOOS) is a knee-specific instrument, developed to assess the patients' opinion about their knee and associated problems. The KOOS evaluates both short-term and long-term consequences of knee injury. It holds 42 items in 5 separately scored subscales; Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL). A higher score is a better outcome.

The score is a percentage score from 0 to 100, 0 representing extreme problems and 100 representing no problems.

Although collected at different timepoints, the average score for each participant is calculated and then the average score for all patients is reported.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=28 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=115 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Postoperative Knee Injury and Osteoarthritis Outcome (KOOS) Scores KOOS Symptoms 4 weeks	37 score on a scale Standard Deviation 11	32 score on a scale Standard Deviation 12
Postoperative Knee Injury and Osteoarthritis Outcome (KOOS) Scores KOOS Quality of Life 4 weeks	18 score on a scale Standard Deviation 15	20 score on a scale Standard Deviation 17
Postoperative Knee Injury and Osteoarthritis Outcome (KOOS) Scores KOOS Symptoms 3 month	32 score on a scale Standard Deviation 14	33 score on a scale Standard Deviation 13
Postoperative Knee Injury and Osteoarthritis Outcome (KOOS) Scores KOOS Quality of Life 3 month	19 score on a scale Standard Deviation 26	37 score on a scale Standard Deviation 20
Postoperative Knee Injury and Osteoarthritis Outcome (KOOS) Scores KOOS Symptoms 6 month	34 score on a scale Standard Deviation 15	34 score on a scale Standard Deviation 13
Postoperative Knee Injury and Osteoarthritis Outcome (KOOS) Scores KOOS Quality of Life 6 month	41 score on a scale Standard Deviation 21	48 score on a scale Standard Deviation 21

SECONDARY outcome

Timeframe: 4 weeks, 3 months, and 6 months after date of surgery

Population: This outcome was measured at three different timepoints (4 weeks, 3 months, and 6 months). Some participants could not be reached for follow-up at certain timepoints, therefore the number of patients analyzed for each timepoint differs.

PainDETECT is a 9-item self-report screening questionnaire developed to detect NeP in conditions like chronic low back pain. PD-Q measures 7 aspects of the quality of the pain experienced, the chronological pattern (time course), and whether or not the pain radiates.

It is scored from 0 to 38, with total scores of <12 considered = nociceptive pain, 13-18 = possible NeP, and >19 = >90% likelihood of NeP. A lower score is a better outcome.

Although measured at multiple time points, the average score for each participant is analyzed, and then the average scores for all participants is calculated and reported.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=10 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) n=91 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Postoperative painDETECT Scores 4 weeks	6.7 score on a scale Standard Deviation 4.1	7 score on a scale Standard Deviation 4.3
Postoperative painDETECT Scores 3 months	6.2 score on a scale Standard Deviation 4.5	3.5 score on a scale Standard Deviation 4
Postoperative painDETECT Scores 6 months	4.9 score on a scale Standard Deviation 7	1.4 score on a scale Standard Deviation 2.4

SECONDARY outcome

Timeframe: Before surgery

Population: some patients did not answer the questionnaire

Statin, gabapentinoid, anticonvulsant, selective serotonin reuptake inhibitor (SSRI), tricyclic antidepressant, serotonin norepinephrine reuptake inhibitor (SNRI), and opioid and non-opioid pain medications.

Outcome measures

Measure	Total Knee Arthroplasty Patients n=173 Participants Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis.	Total Knee Arthroplasty Patients (Non-Stiff) Patients undergoing total knee arthroplasty for osteoarthritis are enrolled in the study. Blood and joint fluid samples will be obtained from patients, and questionnaires will be administered to assess pain and stiffness. Total Knee Arthroplasty: Patients will undergo total unilateral knee arthroplasty for osteoarthritis. Stiffness was defined as ≤ 95° ROM measured with a goniometer at 6 weeks (± 2 weeks).
Types of Preoperative Medications used statins	73 Participants	—
Types of Preoperative Medications used gabapentin	0 Participants	—
Types of Preoperative Medications used anticonvulsants	4 Participants	—
Types of Preoperative Medications used selective serotonin reuptake inhibitors	20 Participants	—
Types of Preoperative Medications used tricyclic antidepressants	1 Participants	—
Types of Preoperative Medications used serotonin-norepinephrine reuptake inhibitors	4 Participants	—

Adverse Events

Total Knee Arthroplasty Patients

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Meghan Kirksey

Hospital for Special Surgery, Anesthesiology

Phone: 2126061036

Email: KirkseyM@hss.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place