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

Persistent pain and joint stiffness after surgery may interfere with recovery and adversely affect quality of life in up to 40% of patients who have undergone total knee arthroplasty. There is growing evidence that inflammation as well as other medical and psychological factors may be associated with osteoarthritis severity, progression, and associated pain severity. This study aims to identify clinical, biological, and psychological factors that contribute to and predict the development of these complications. Identification of such factors may allow us to target preventative measures to the patients at highest risk of persistent postoperative pain and joint stiffness.

Study Overview

• Status: Completed
• Conditions: Pain; Joint Stiffness
• Intervention / Treatment: Procedure: Total Knee Arthroplasty

• Study Type: Observational
• Enrollment (Actual): 179

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital For Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Hospital for Special Surgery patients scheduled to undergo unilateral total knee arthroplasty under regional anesthesia.

Description

Inclusion Criteria:

• Elective primary unilateral total knee arthroplasty
• Osteoarthritis with radiologic evidence of "severe narrowing" and/or "bone on bone" in the affected joint
• Patients of surgeons who have agreed to participate in the study
• Age > 18 years
• American Society of Anesthesiologists (ASA) Physical Status 1-3
• Regional anesthesia
• Epidural patient-controlled analgesia (PCA) for postoperative pain
• Adductor canal block for postoperative pain

Exclusion Criteria:

• Contraindication to regional anesthesia, NSAIDs, dexamethasone or acetaminophen
• Use of general anesthesia
• History of >6 weeks of daily opioid use and/or any use of non-prescribed opioids
• Preoperative oral steroid use in the past 6 months
• Intra-articular steroid injection within one month of scheduled surgery in affected joint
• Non-English speakers
• Pre-existing diagnosis of rheumatic disease or autoimmune disease (e.g. rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, multiple sclerosis, Type I diabetes)
• Peri-articular injections or infusions for postoperative pain
• Diagnosis of crystalline arthropathy
• Diagnosis of osteonecrosis
• Active infection or use of antibiotics
• Pregnant women

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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. Pain type and severity will be assessed at baseline (enrollment), 4 weeks, 3 months, and 6 months postoperatively.	Procedure: Total Knee Arthroplasty; Patients will undergo total unilateral knee arthroplasty for osteoarthritis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of Persistent Postoperative Pain Using the Numeric Rating Scale (NRS)	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.	6 months after date of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients Who Experienced Postoperative Joint Stiffness	The number of patients that experienced postoperative joint stiffness, defined as ≤95 degrees range of motion.	6 weeks after date of surgery
Postoperative Knee Range of Motion	Range of motion at 6 weeks postoperative. Measured as flexion minus extension. Measured in degrees.	6 weeks after date of surgery
NRS Pain at Rest on POD1	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.	1 day after surgery
NRS Pain With Movement on POD1	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.	1 day after surgery
Worst NRS Pain on POD1	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.	1 day after surgery
Least NRS Pain on POD1	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.	1 day after surgery
NRS Pain at Rest on POD2	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.	2 days after surgery
NRS Pain With Movement on POD2	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.	2 days after surgery
Worst NRS Pain on POD2	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.	2 days after surgery
Least NRS Pain on POD2	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.	2 days after surgery
NRS Pain at Rest 4 Weeks After Surgery	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.	4 weeks after surgery
NRS Pain With Movement 4 Weeks After Surgery	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.	4 weeks after surgery
Worst NRS Pain 4 Weeks After Surgery	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.	4 weeks after surgery
Least NRS Pain 4 Weeks After Surgery	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.	4 weeks after surgery
NRS Pain at Rest 3 Months After Surgery	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.	3 months after surgery
NRS Pain With Movement 3 Months After Surgery	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.	3 months after surgery
Worst NRS Pain 3 Months After Surgery	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.	3 months after date of surgery
Least NRS Pain 3 Months After Surgery	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.	3 months after date of surgery
NRS Pain at Rest 6 Months After Surgery	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.	6 months after date of surgery
Least NRS Pain 6 Months After Surgery	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.	6 months after date of surgery
Worst NRS Pain 6 Months After Surgery	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.	6 months after date of surgery
Postoperative Knee Injury and Osteoarthritis Outcome (KOOS) Scores	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.	4 weeks, 3 months, and 6 months after date of surgery
Postoperative painDETECT Scores	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.	4 weeks, 3 months, and 6 months after date of surgery
Types of Preoperative Medications	Statin, gabapentinoid, anticonvulsant, selective serotonin reuptake inhibitor (SSRI), tricyclic antidepressant, serotonin norepinephrine reuptake inhibitor (SNRI), and opioid and non-opioid pain medications.	Before surgery

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Investigators: Principal Investigator: Meghan Kirksey, MD, PhD, Hospital for Special Surgery, New York

Publications and helpful links

General Publications

• Sideris A, Malahias MA, Birch G, Zhong H, Rotundo V, Like BJ, Otero M, Sculco PK, Kirksey M. Identification of biological risk factors for persistent postoperative pain after total knee arthroplasty. Reg Anesth Pain Med. 2022 Mar;47(3):161-166. doi: 10.1136/rapm-2021-102953. Epub 2021 Dec 17.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): August 28, 2017
• Study Completion (Actual): February 28, 2018

Study Registration Dates

• First Submitted: December 8, 2015
• First Submitted That Met QC Criteria: December 9, 2015
• First Posted (Estimated): December 10, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Cytokines
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis
• Other Study ID Numbers: 2015-361

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO