Incidence of Persistent Pain After Knee Arthroplasty: A Nationwide Cross-sectional Survey Study
Conditions: Persistent Postsurgical Pain, Arthritis Knee, Neuropathic Pain, Opioid Use
Sponsor: University Hospital Bispebjerg and Frederiksberg

 
Incidence of persistent pain after knee arthroplasty: A nationwide cross-
sectional survey study 
 
Jens Laigaard, MD, PhD-student, Dept. of Orthopaedic Surgery, Bispebjerg Hospital 
Lone Nikolajsen, MD, D.M.Sc., Professor, Dept. of Anaesthesia, Aarhus University Hospital 
Saber Muthanna Saber, MD, PhD-student, Dept. of Orthopaedic Surgery, Bispebjerg Hospital 
Ole Mathiesen, MD, PhD, Professor, Dept. of Anaesthesiology, Zealand University Hospital, Køge 
Troels Haxholdt Lunn, MD, PhD, D.M.Sc., Associate professor Dept. of Anaesthesia, Bispebjerg Hospital, 
Copenhagen 
Martin Lindberg-Larsen, MD, PhD, Associate professor, Dept. of Orthopaedic Surgery and Traumatology, 
Odense Hospital 
Søren Overgaard, MD, D.M.Sc., Professor, Dept. of Orthopaedic Surgery, Bispebjerg Hospital 
 
Keywords: Chronic pain; Post-traumatic pain; Persistent postoperative pain; Neuropathic pain; Knee 
replacement 
 
Funding: The project is fully funded by the Dept. of Orthopaedic Surgery, Bispebjerg Hospital, including 
salary to main investigator Jens Laigaard, salary to employee from the Danish Health Data Authority for 
extraction of relevant CPR numbers (approx. 10.000 DKK) and fee for sending surveys with ‘Digital Post’ 
through REDCap. 
The budget for the full PhD project is attached to this document (appendix 4).  
 
Date: June 2, 2023 
 
Word count: 1808 
 
 

 
Introduction 
Knee arthroplasty (KA) is an effective treatment for patients with knee osteoarthritis when non-opioid 
analgesics and physiotherapy cannot control their pain.1 Generally, KA is safe and provides satisfactory 
results, but previous studies have found that a considerable proportion of patients suffer from persistent pain 
after surgery.2,3 
Each year, more than 10,000 and 1.1 million primary KAs are performed in Denmark4 and worldwide,5 
respectively. As these numbers increase, more and more patients will suffer from persistent postsurgical 
pain. Generally, chronic pain is a substantial clinical challenge because effective treatments are lacking.6 To 
recognise the magnitude of the problem, but also to allow surgeons to accurately inform their patients of the 
long-term risks, it is important to know the incidence of persistent postsurgical pain. 
We are not aware of previous assessments of long-term pain outcomes in unselected Danish patients 
operated with KA. The most widely used numbers originates from a systematic review published in 2012 
that used data collected in various countries between 1995-2006.2 An updated investigation is important for 
several reasons. First, surgical techniques and equipment have evolved over the years. Second, introduction 
of standard treatment with high-dose glucocorticoids should, in theory, have reduced central sensitisation, 
which is a key aspect of persistent postsurgical pain.7,8 Third, implementation of early mobilisation and other 
enhanced recovery after surgery (ERAS) elements have reduced the mean length of hospital stay from 
around 10 days in 2000 to a single day in 2021.4  
For these reasons, we aim to investigate the satisfaction and incidence of persistent pain after KA for 
osteoarthritis.  
 
 

 
Methods 
The study is registered at the capital region of Denmark’s regional research listing (Pactius) with identifier P-
2023-4, approved 4 January 2023. This protocol is registered at ClinicalTrials.gov and is currently under 
review. The resulting paper will be reported according to the CROSS checklist for standardised reporting of 
survey studies.9 Wherever needed, a trained linguist translated questions from English to Danish and vice 
versa. The Danish and an English version of the questionnaire will be available in the final publication. 
Study design: This study is a nationwide cross-sectional survey. 
Patient involvement: A panel of KA patients helped develop the questionnaire, i.e., testing and selecting the 
questions. 
Questionnaire: The questionnaire is composed of 22 questions, however patients answering “No” to 
question 3 skips questions 4-17 concerning pain in the operated knee. Only questions 3, 4, 20, and 21 are 
mandatory because we wanted to avoid non-respondents. The contact letter in Danish (S1) and full 
questionnaire in Danish (S2) and English (S3) can be found in the supplementary material. Contact 
information for the first author (JL) is supplied in the contact letter and the header of the questionnaire, in 
case the patients have difficulties with filling in the questionnaire, believe they have been contacted 
mistakenly etc. We used similar or identical questions to those in a survey conducted in 2004 to increase our 
ability to compare results (i.e., questions 3-5, 8, 10 and 18).10  
The 1st question assesses overall satisfaction with surgery and have been translated directly from the 
questionnaire used by the Swedish Arthroplasty Register to enable direct comparison.3  
Question 2 assesses willingness to repeat surgery, as described by Chestworth et al..11  
Question 3 assesses pain frequency with the same response options as the 2004 survey.10 This question is 
mandatory due to branching purposes, i.e. respondents without pain can skip questions 4-17. 
Question 4 is the 11-point numerical rating scale (NRS) for knee pain, which is widely used and 
recommended.12,13 To facilitate comparison with other studies, we assessed average pain in the last week.12 
This question is also mandatory because it is our primary outcome. 
Question 5-9 is the pain dimension of the likert-scale version 3.1 Western Ontario and McMaster 
Universities Osteoarthritis Index (WOMAC).14 The instrument is validated for osteoarthritis patients and 
specifically recommended by the International Association for the Study of Pain (IMMPACT).13  
Question 10 assesses pain interference on everyday activities. Pain interference is often included in core 
outcome sets for clinical trials13,15 and it is recommended to use disease-specific interference.13  

 
Question 11-17 are the Douleur Neuropathique 4 questions (DN4) interview, which can be used to estimate 
the number of patients with ‘possible’ neuropathic pain.16,17 We chose to the DN4 interview over other 
neuropathic pain measures because it is widely used and validated, short, and available in Danish (from 
www.mapi-trust.org).16  
Question 18 assesses other chronic pain conditions with an open text field, which we will later categorise. 
We believe this is more accurate than allowing patients to categorise their pain condition from a predefined 
list of options. 
Question 19 assesses patient-reported use of analgesics, including if the analgesics are taken for pain in the 
operated knee or not. Again, the type of analgesics is typed into an open text field, as to not restrict 
respondents to specific medications and to enable responses with typos. 
Questions 20 and 21 are on the patient’s current height and weight, recently found to be valid in a Danish E-
survey setting.18  
Finally, in question 22 we ask for permission to contact respondents again later. 
Sample characteristics: Eligible patients are all adult (18 years or older) patients operated with primary 
total or medial unicompartmental KA for osteoarthritis between August 1 and November 30, 2023. Legally 
incompetent citizens, i.e., persons with a legal guardian, will not be asked to participate. 
For total KA, we will identify patients from the Danish National Patient Register through the Danish Health 
Data Authority (SKS-code DM17 [knee osteoarthritis] + KNGB20, KNGB30 or KNGB40 [primary total 
knee arthroplasty]). 
For medial unicompartmental KA, we will identify patients from the Danish National Patient Register 
through the Danish Health Data Authority (SKS-code DM17 [knee osteoarthritis] + KNGB01 or KNGB11 
[primary medial unicompartmental knee arthroplasty]). 
The sample size calculation is based on the primary outcome in total KA patients. With an estimated 16% 
incidence of the primary outcome3 and a 70% response rate,19 3172 patients are needed to yield a 95% 
confidence interval of 3 percentage points (14.6-17.6). In our opinion, this level of certainty is appropriate 
because differences less than this, may be hard to interpret by clinicians and patients. Sampling patients that 
were operated during 4 months outside holiday season should yield approximately this number of identified 
patients.4  
Baseline data of respondents and non-respondents are gathered from the Danish Knee Arthroplasty Register. 
To evaluate the generalisability of the study, we will report the respondents’ baseline data and compare them 
to the non-respondents in Table 1. 

 
Survey administration: In an encrypted fashion, the survey will be sent via ‘Digital Post’ which is linked to 
the unique Civil Registration (CPR) number using the Research Electronic Data Capture (REDCap) software 
(www.project-redcap.org). A reminder will be sent to non-respondents 14 days after the first letter. 
Remaining non-respondents are sent a text-message if their telephone number is registered in the electronic 
patient file. 
For questions with an open text field option, two authors (JL, SS) will independently categorise the 
responses to minimise errors. 
Study preparation: We will not advertise the survey and respondents are not rewarded for participation. 
Ethical considerations: The local institutional review board approved the study, and the Danish Health Data 
Authority will provide contact information for potential respondents. Telephone numbers for non-
respondents are found by searching the CPR number in the electronic patient files, but without accessing the 
patients’ health data. According to Danish legislation, approval from the national ethics committee is neither 
required nor possible to obtain for survey studies (see attached ‘exempt from notification’ letter from the 
Danish national ethics committee, S5). 
Because we will link survey responses with perioperative data from the Danish Knee Arthroplasty Register, 
responses are not anonymous. However, only the authors will have access to confidential information and 
data will be anonymised as soon as possible. Until then, the data are stored pseudonymised at a logged and 
encrypted drive. 
Statistical analyses: The main outcome is the number of patients with moderate or severe persistent 
postsurgical pain in the operated knee, defined as patients with a numerical rating scale (NRS) score higher 
than 3.20 We dichotomised the NRS score for our primary outcome because we believe this is more 
intuitively understood by patients and clinicians. The main outcome will be reported as percentage of all 
patients with 95% confidence interval, calculated with assumed binomial distribution: 
p ± 1.96 √𝑝 (1 −𝑝)
𝑛
 
Categorical variables, including the individual questions of WOMAC pain domain and DN4 interview, will 
be reported directly as number of patients (percentage of all patients). The raw NRS score, height and weight 
are continuous variables and will be reported as median (interquartile range [IQR]) number of respondents. 
The five questions in the WOMAC pain domain can be scored 0-4, where 0 is ‘none’ and 4 is ‘extreme’. 
This results in an overall score of 0-20, which will be reported as median (IQR). 

 
Each of the seven questions in the DN4 interview can be scored 0/1 (no/yes), which results in an overall 
score of 0-7. A score ≥3 constitutes ‘possible’ neuropathic pain.16,17 Both the median (IQR) DN4 interview 
score and number of patients (percentage of all patients) with possible neuropathic pain will be reported. 
We do expect some missing data because incomplete questionnaires may be submitted. Generally, responses 
will not be imputed. However, we will impute values to calculate summary scores of the WOMAC pain 
domain and DN4 interview as the median of the reported values within the instrument. 
We do not plan to adjust for non-representativeness, but as previously mentioned, baseline characteristics 
(age, sex, and ASA score) and surgical details (type of anaesthesia, operation length, use of local infiltration 
analgesia (LIA), use of cement, and surgical complications) of respondents and non-respondents are 
presented in Table 1. 
Data is handled in the most recent version of R (www.r-project.org).21 
 
Knowledge dissemination 
The survey will be fully reported in an international peer-reviewed journal. In addition, the responses from 
this survey will be pooled with responses from a similar survey on hip pain. The combined data will be used 
in two additional studies: 1) to validate the use of prescription registries on analgesic for identifying patients 
with persistent postsurgical pain,22 and 2) to investigate associations between weight and weight-change and 
the different outcomes. Both will be published in peer-reviewed journals.  
We seek to make the papers freely available (e.g., as preprint at www.medrxiv.org or through open-access 
publication) and to store the full dataset at the Danish national archive (www.rigsarkivet.dk). Moreover, the 
results will be presented at meetings and conferences, predominantly for orthopaedic surgeons, anaesthetists, 
pain specialists, and other health-care personnel working with this patient group. 
The systematic review from 2012 that we seek to build on is widely used, even though the data may be 
outdated.2 This study is necessary to avoid false assumptions regarding the contemporary risk of persistent 
pain after KA. We are certain that the results from this study will be used by clinicians to guide patients in 
their decision to undergo KA or not. 
 
 

 
References 
1. Gademan, M. G. J., Hofstede, S. N., Vliet Vlieland, T. P. M., Nelissen, R. G. H. H. & Marang-van de 
Mheen, P. J. Indication criteria for total hip or knee arthroplasty in osteoarthritis: a state-of-the-science 
overview. BMC Musculoskelet. Disord. 17, 463 (2016). 
2. Beswick, A. D., Wylde, V., Gooberman-Hill, R., Blom, A. & Dieppe, P. What proportion of patients 
report long-term pain after total hip or knee replacement for osteoarthritis? A systematic review of 
prospective studies in unselected patients. BMJ Open 2, e000435 (2012). 
3. W-Dahl, A. et al. Swedish Joint Arthroplasty Register Annual report 2022. (2022). 
4. DKR. Danish Knee Arthroplasty Register, National Annual Report. (2021). 
5. Organisation for Economic Co-operation and Development. OECD Health Statistics. (2023). 
6. Wylde, V. et al. Systematic review of management of chronic pain after surgery. Br J Surg 104, 1293–
1306 (2017). 
7. Glare, P., Aubrey, K. R. & Myles, P. S. Transition from acute to chronic pain after surgery. Lancet 393, 
1537–1546 (2019). 
8. Finnerup, N. B., Nikolajsen, L. & Rice, A. S. C. Transition from acute to chronic pain: a misleading 
concept? Pain 163, e985–e988 (2022). 
9. Sharma, A. et al. A Consensus-Based Checklist for Reporting of Survey Studies (CROSS). J Gen Intern 
Med 36, 3179–3187 (2021). 
10. Nikolajsen, L., Brandsborg, B., Lucht, U., Jensen, T. S. & Kehlet, H. Chronic pain following total hip 
arthroplasty: a nationwide questionnaire study. Acta Anaesthesiol Scand 50, 495–500 (2006). 
11. Chesworth, B. M., Mahomed, N. N., Bourne, R. B., Davis, A. M. & Ojrr Study Group. Willingness to go 
through surgery again validated the WOMAC clinically important difference from THR/TKR surgery. J 
Clin Epidemiol 61, 907–18 (2008). 
12. Chiarotto, A. et al. Pain Measurement in Rheumatic and Musculoskeletal Diseases: Where To Go from 
Here? Report from a Special Interest Group at OMERACT 2018. J Rheumatol 46, 1355–1359 (2019). 
13. Dworkin, R. H. et al. Core outcome measures for chronic pain clinical trials: IMMPACT 
recommendations. Pain 113, 9–19 (2005). 
14. Bellamy, N., Buchanan, W. W., Goldsmith, C. H., Campbell, J. & Stitt, L. W. Validation study of 
WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to 
antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15, 1833–40 
(1988). 
15. Wylde, V., MacKichan, F., Bruce, J. & Gooberman-Hill, R. Assessment of chronic post-surgical pain 
after knee replacement: development of a core outcome set. Eur J Pain 19, 611–20 (2015). 
16. Bouhassira, D. et al. Comparison of pain syndromes associated with nervous or somatic lesions and 
development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 114, 29–36 (2005). 
17. Finnerup, N. B. et al. Neuropathic pain: an updated grading system for research and clinical practice. 
Pain 157, 1599–1606 (2016). 
18. Neermark, S. et al. Validation and calibration of self-reported height and weight in the Danish Health 
Examination Survey. Eur J Public Health 29, 291–296 (2019). 
19. Christensen, A. I. et al. The Danish National Health Survey: Study design, response rate and respondent 
characteristics in 2010, 2013 and 2017. Scand J Public Health 50, 180–188 (2022). 
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simple, universal outcome. Anaesthesia 68, 400–412 (2013). 
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Appendix 1 – Contact letter (Danish) 
It is not possible to upload foreign language text to ClinicalTrials.gov. 
Appendix 2 – Survey in Danish 
It is not possible to upload foreign language text to ClinicalTrials.gov. 
Appendix 3 – Survey in English 
If you experience any issues responding to the survey, please contact Jens Holm Laigaard by telephone: 42 
61 73 77 or email jens.holm.laigaard@regionh.dk 
 
Satisfaction 
1) How satisfied are you with the outcome of your knee replacement surgery? 
Very satisfied, Satisfied, Neither satisfied nor dissatisfied, Dissatisfied, Very dissatisfied 
 
2) Knowing what your knee replacement surgery did for you, if you could go back in time, would you still 
have undergone this surgery? 
Yes, No, Uncertain 
 
Pain in the operated knee 
3) [Mandatory] Do you still have pain in the operated knee? 
Yes, constantly; Yes, daily; Yes, a few times a week; Yes, more rarely; No 
 
4) [Mandatory if 1 ≠ ”No”] Please rate your pain in the operated knee by indicating the number that best 
describes your pain on average during the last week. 
0 means ‘No pain’ and ‘10’ means ‘Pain as bad as you can imagine’. 
0 1 2 3 4 5 6 7 8 9 10 
 
What amount of knee pain have you experienced the last week during the following activities?  
5) Walking on a flat surface 
None 
Mild 
Moderate 
Severe 
Extreme 
6) Going up or down stairs 
None 
Mild 
Moderate 
Severe 
Extreme 
7) At night while in bed 
None 
Mild 
Moderate 
Severe 
Extreme 
8) Sitting or lying 
None 
Mild 
Moderate 
Severe 
Extreme 
9) Standing upright 
None 
Mild 
Moderate 
Severe 
Extreme 
 
Activities of daily living 
10) In total, how much does the pain in the operated knee bother you in your everyday life? 
Not at all, A little, Some, Much, Very Much 
 
Does the pain have one or more of the following characteristics? 
11) Burning 
Yes 
No 
12) Painful cold 
Yes 
No 
13) Electric shocks 
Yes 
No 

 
 
Is the pain associated with one or more of the following symptoms in the same area? 
14) Tingling 
Yes 
No 
15) Pins and needles 
Yes 
No 
16) Numbness 
Yes 
No 
17) Itching 
Yes 
No 
 
Other pain  
18) Do you have chronic pain, other than from your operated knee? 
Yes; No 
[If yes] Please describe your pain condition: _____ 
 
Analgesic use 
19) Do you take analgesic medication(s) daily or almost daily? 
Yes; due to pain in the operated knee; Yes, due to other pain; No  
[If yes] Which medication(s)?: _____  
 
Please insert your height and weight 
20) [Mandatory] Weight: _____ (kg) 
21) [Mandatory] Height: _____ (cm) 
 
Contact 
22) Can we contact you again, e.g. regarding your responses? 
Yes; No 
[if yes] Please insert your contact information (telephone number, email address): _____ 
 
Thank you so much for your participation. Your responses have been saved and you can exit the site.  
You are welcome to contact Jens Holm Laigaard by telephone 42 61 73 77 or email 
jens.holm.laigaard@regionh.dk if you have questions or comments regarding the survey. 
 
Appendix 3 – Budget in Danish 
It is not possible to upload foreign language text to ClinicalTrials.gov. 

 
Appendix 5 – Exempt from notification