Pain Sensitization in Patients With Symptomatic Atrial Fibrillation Compared With Asymptomatic Patients
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Region Örebro County

 
 
 
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Pain sensitization in patients with symptomatic atrial fibrillation 
compared with asymptomatic patients 
Anna Björkenheim, MD, PhD1, Adam Jackson, BSc1 Ole Fröbert, MD, PhD1, Dennis Boye 
Larsen BSc PhD2, Lars Arendt Nielsen, MSci, PhD, DMSci2 
 
1. Department of Cardiology, Faculty of Medicine and Health, Örebro University, Sweden. 
2. SMI, Faculty of Medicine, Aalborg University, Aalborg, Denmark. 
 
 
 
Correspondence: 
Anna Björkenheim, MD, PhD 
 
Ole Fröbert, MD, PhD 
Department of Cardiology  
 
Department of Cardiology 
Örebro University Hospital 
 
Örebro University Hospital 
701 85 Örebro, Sweden 
 
 
701 85 Örebro, Sweden 
Telephone +46 19 602 54 59 
 
Telephone +46 602 54 13 
Fax +46 19 602 24 07 
 
 
Fax +46 19 602 54 38 
Email: anna.bjorkenheim@regionorebrolan.se 
Email: ole.frobert@regionorebrolan.se 
 
 

 
 
 
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Abstract 
Background 
Atrial fibrillation (AF) is the most common sustained arrhythmia and the number of patients 
with AF is expected to increase substantially in the coming decades. One third of patients 
with AF report no AF-associated symptoms, but up to one fourth report severe symptoms 
such as chest pain. It is well recognized, but unclear why patients’ experience of AF-related 
symptoms, including chest pain, varies so much. Patients with chronic pain show a high 
degree of central sensitization, i.e. facilitated pain responses to repeated painful stimulation 
and impaired conditioned pain modulation, compared with controls. It is possible that 
patients with symptomatic AF may have developed pronounced pain sensitization even in 
the absence of chest pain as a symptom. No previous study has investigated pain 
sensitization in patients with AF. 
Objective and methods 
The primary objective is to assess differences in pain sensitization in patients with 
symptomatic AF compared with patients with asymptomatic AF. Secondary objectives are to 
study the association of age, sex, AF duration, comorbidities and health-related quality of life 
to pain sensitization. A total of 30 patients with permanent AF (15 symptomatic and 15 
asymptomatic) will be recruited. Patients will complete an AF-specific symptom score and a 
generic health-related quality of life questionnaire, and physicians will assess AF-related 
symptoms. Quantitative sensory testing recordings will be collected by pressure algometry. 
Assessment of temporal summation of pressure pain and conditioning pain modulation will 
be used to investigate the involvement of pain sensitization. 
Clinical relevance 

 
 
 
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This preliminary pilot study will be used to estimate sample size for a larger study in which 
both patients and control subjects will be recruited, to further investigate whether patients 
with symptomatic AF have increased pain sensitization compared with patients with 
asymptomatic AF and controls. The studies may have an impact on individualized 
management of patients with AF in the future.  
Trial registration 
The study protocol is registered with ClinicalTrials.gov (NCT…) 
 
Keywords 
Atrial fibrillation, Symptoms, Quality of life, Pain, Conditioning pain modulation, Temporal 
summation 
 
 

 
 
 
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Abbreviations 
AF 
 
Atrial fibrillation 
AF6 
 
Atrial fibrillation 6 questionnaire 
CPM 
 
Conditioned pain modulation 
ECG 
 
Electrocardiogram 
SF-36 
 
Short form 36 health survey 
VAS 
 
Visual analogue scale 
 

 
 
 
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Introduction 
Background 
Atrial fibrillation (AF) is the most common sustained arrhythmia affecting approximately 3% 
of adults aged 20 years or older in Western countries, and is expected to increase further in 
the coming decades(1). The presence of AF is independently associated with an increased 
risk of all-cause mortality and morbidity, largely due to stroke and heart failure, dementia, 
symptoms, and impaired quality of life(2-7). The management of AF aims to prevent AF-
related complications using oral anticoagulation therapy in patients with a high risk of stroke 
and to reduce symptoms and improve health-related quality of life using a rate (slowing of 
the ventricular rate) or rhythm control (restoration and maintenance of normal sinus 
rhythm) strategy(8). 
About one third of patients with AF report no AF-associated symptoms, but up to one fourth 
of patients report severe symptoms such as palpitations, dyspnea, chest discomfort or pain, 
dizziness and syncope(9-11). In previous studies 9 to 15% of patients with permanent AF 
reported chest pain as an AF-related symptom(12, 13). In addition, one third of patients with 
symptomatic AF suffer from psychological distress (anxiety and/or depression), which may 
also worsen symptoms of AF(11, 14).  
It is well recognized, but remains unclear why some patients with AF are asymptomatic 
whereas others are severely symptomatic. Several studies have evaluated the relationship 
between patient characteristics and the presence of AF symptoms, and have found that 
asymptomatic AF is more frequent in men than in women, and in older age(15, 16). 
Inconsistent results have been reported for associations between asymptomatic AF and 
comorbidities(17). Patients with all types of AF can be asymptomatic, but asymptomatic AF 

 
 
 
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is more common in patients with permanent AF(18). The situation is further complicated by 
the fact that asymptomatic AF episodes are common even in highly symptomatic patients 
and that AF interventions such as pulmonary vein isolation increase asymptomatic 
episodes(19). In conclusion, little is known of the pathophysiological mechanisms underlying 
AF symptomatology but both somatic and psychological factors are likely involved. 
The authors have previously shown that central nervous system responses to visceral and 
somatosensory nociceptive input are altered in patients who have angina despite normal 
coronary angiograms compared to healthy volunteers(20). Patients with chronic pain 
conditions such as osteoarthrosis, chronic pancreatitis and irritable bowel syndrome, show a 
high degree of central sensitization, i.e. facilitated pain responses to repeated painful 
stimulation and impaired conditioned pain modulation (CPM) compared with controls(21-
24). Furthermore, these patients often show a discrepancy between pain intensity and 
objective measures of disease severity and healthcare personnel often underestimate 
patients’ pain intensity(25, 26). It is also well-known that stress influences pain sensitivity 
and has been correlated to hyperalgesia in patients with ischemic heart disease(27, 28). It is 
possible that patients with symptomatic AF have developed pronounced pain sensitization 
even in the absence of chest pain as a symptom, and in particular facilitated pain responses 
to repeated painful stimulation, i.e. temporal summation of pressure pain. No previous 
study has investigated pain sensitization in patients with AF, neither in patients with or 
without chest pain as a symptom. 
 
 
Purpose 

 
 
 
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The primary objective is to assess differences in pain sensitization in patients with 
symptomatic AF compared with patients with asymptomatic AF. 
 
Hypothesis 
We hypothesize that central sensitization is involved in sensing of and discomfort from AF in 
symptomatic patients, involving neural pathways also involved in perceiving pain. Because of 
shared pathways, we further hypothesize that patients with AF symptoms have lower pain 
thresholds than asymptomatic patients with AF. 
 
Clinical relevance 
It is well recognized, but unclear why patients’ perception of AF varies so much. This 
preliminary pilot trial will be used to estimate sample size for a larger trial, in which both 
patients and control subjects will be recruited, to further investigate whether patients with 
symptomatic AF have increased pain sensitization compared with patients with 
asymptomatic AF and controls. The studies may have an impact on individualized 
management of patients with AF in the future. 
 
 

 
 
 
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Material and methods 
Study design 
Single-center cohort study. 
 
Subject inclusion criteria 
Study participants will be recruited from a database of all patients aged 20 years or older 
with a diagnosis of AF from 1 January 2015 to 31 December 2018 in Örebro County (more 
than 10 000 patients) extracted from the National Patient Register, that covers all in-patient 
and outpatient physician visits from both private and public caregivers, and the Medrave 4 
patient statistics software that is used in all public general practices in the county. The 
diagnosis of AF was based on at least one electrocardiogram (ECG) characterized by an 
absolutely irregular RR interval, no distinct P waves and an atrial cycle length of less than 200 
ms. By accepted convention, an episode with these ECG characteristics lasting for at least 30 
seconds was diagnostic of AF(8). Permanent AF is defined as persistent AF that is accepted 
by both the patient and the physician and for which no further attempts to restore or 
maintain normal sinus rhythm will be undertaken(8). 
Further inclusion criteria: 
- 
Male or female subjects ≥ 20 years and ≤ 75 year, primarily 60 to 70 years old.  
- 
Permanent AF 
- 
Previously completed AF-specific symptoms questionnaire Atrial fibrillation 6 
questionnaire (AF6) 
- 
Written informed consent 
Subject exclusion criteria 

 
 
 
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- 
Paroxysmal or persistent AF (AF that terminates spontaneously or with intervention, 
respectively(8)) 
- 
Previous pulmonary vein isolation 
- 
Psychiatric or cognitive condition 
- 
Pregnancy 
- 
Previous/current drug or alcohol abuse 
- 
Previous neurological or concomitant musculoskeletal disorders 
- 
Continuous analgesic medication 
Examinations 
All potential patients will receive written information about the study and will thereafter be 
contacted by telephone and offered an outpatient visit to a physician at the Department of 
cardiology, Örebro University Hospital, Örebro, Sweden. After obtaining written informed 
consent, patients will be asked to complete the AF6 and the Short form 36 health survey (SF-
36) questionnaires before a 12-lead ECG is obtained. Patients will also be asked to rate the 
symptom chest pain on the Visual analogue scale (VAS) (0 to 10) and to draw the pain area 
on a body chart. Comorbidities, medications and duration of AF will be documented and a 
routine clinical examination will be performed, and the modified European Heart Rhythm 
Association symptoms scale assessed. Quantitative sensory testing recordings will be 
collected by pressure algometry. The patients will be asked not to take any analgesic 
medication 24 hours before the examination. No follow-up visits are scheduled. Subjects will 
be divided into two groups based on their previous AF6 symptom scores; asymptomatic 
patients with an AF6 sum score of 0, and symptomatic patients with an AF6 sum score of 
≥30. 

 
 
 
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Symptom assessment 
The patient-reported AF6 questionnaire includes six items (breathing difficulties at rest and 
upon exertion, limitations in day-to-day life, feeling of discomfort, tiredness and 
worry/anxiety due to AF) and a score of 0 (no symptoms) to 10 (severe symptoms) is 
reported for each item, and all scores are added into a single sum score. Sum scores range 
from 0 to 60, with higher values reflecting more severe AF-related symptoms. The AF6 
includes a recall period of the last 7 days(29, 30). 
The physician-assessed modified European Heart Rhythm Association symptoms scale is 
used for symptom severity assessment in patients with AF, relating specifically to the time 
when patients feel symptoms of AF. Patients in class I are considered to have no symptoms, 
in class IIa mild, class IIb moderate, class III severe and in class IV disabling symptoms of 
AF(8, 31). 
 
Health-related quality of life 
The patient-reported SF-36 has a recall period of four weeks and consists of 36 items 
assessing eight domains ranging from 0 to 100, with higher values indicating better health-
related quality of life. The eight domains generate two summary measures: the physical 
component summary and the mental component summary scores, which will be used to 
assess health-related quality of life(32). 
 
Clinical examination 

 
 
 
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A cardiovascular examination including blood pressure measurement will be performed. The 
blood pressure will be measured after 15 minutes of rest by an automatic 
sphygmomanometer. 
 
Quantitative sensory testing 
Pressure pain threshold 
The pressure pain thresholds (PPTs) is defined as the minimal amount of pressure where a 
sense of pressure first changes to pain. Participants will be instructed to press the ‘stop’ 
button of the algometer as soon as the pressure results in the first sensation of pain. 
Pressure will be increased at a rate of approximately 30 kPa/s. The 1-cm2 probe of the 
handheld pressure algometer (Somedic AB, Sweden) will be placed perpendicularly to the 
skin. PPTs will be assessed over the sternum at the level of intercostal spaces 3–5 and over 
the tibia bone(27). The PPTs will be measured three times on each site, and the mean of the 
three measurements will be used for statistical analysis. Low PPTs indicate sensitization. 
 
Temporal summation of pressure pain 
A Pin prick (tip area, 0.2mm2) with a weighted load (Aalborg University, Denmark) will be 
used to induce temporal summation of pressure pain (TSP) as previously conducted in other 
pain studies(33-35). A force of 50 g will be applied once over the sternum at the level of 
intercostal spaces 3–5 and over the tibia bone and the patient will be asked to rate the pain 
intensity on the VAS (0 to 10). Then 10 consecutive stimuli will be applied (1 s interval 
between consecutive stimuli) to the same site and the subject will be asked to rate the pain 
intensity of the last stimulation on the VAS. TSP will be calculated as the difference in the 

 
 
 
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pain intensity between the first and the last stimulation. High TSP scores indicate facilitated 
temporal summation. 
 
Conditioning pain modulation 
The right hand up to the wrist will be immersed into stirred cold water (2–4 ◦C, measured in 
the water) for 2 min (the so called cold pressor test). Before the immersion the PPTs will be 
assessed from the sternum and the tibial bone, at the end of the two min immersion the 
PPTs will be assessed again and this will be repeated again 10 min after the hand is 
withdrawn from the water. The conditioning pain modulation index will be assessed as the 
increase in PPTs during the immersion as compared to the pre-immersion PPTs. The lower 
the difference is the more sensitization. 
 
Primary endpoint 
The primary objective is to assess differences in pain sensitization in patients with 
symptomatic AF compared with patients with asymptomatic AF. 
 
Secondary endpoint 
Secondary objectives are to study the association of age, sex, AF duration and comorbidities 
and physical and mental component summary scores to pain sensitization. 
 
Ethics approval 
The study protocol is approved by the Swedish Ethical Review Authority (2020-01619). 
Statistics and data management 

 
 
 
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Data collected during the study will be coded. 
Statistical analysis 
Data will be presented as mean and standard deviation. A one-way ANOVA will be used for 
demographic parameters and to compare the groups. Pearson correlations will be used for 
linear estimates and Spearman´s correlations for non-linear parameters. All analyses will be 
adjusted for age. Analyses will be performed using IBM SPSS Statistics 22 (Armonk, NY, USA) 
or STATA release 14 (College Station, TX, USA). 
Sample size calculations 
As no previous trial of pain sensitization in patients with AF has been performed, a pilot trial 
is necessary to calculate sample size for a larger study. 
Database and Case report form 
A case report form will be filled out and coded for each patient. The investigators are 
responsible for ensuring the accuracy, completeness, legibility and timeliness of the data 
recorded in the case report forms. 
Documentation and data collection 
Criteria for inclusion, informed consent, the decision to include the subject and the subject 
number will be documented in the subject’s hospital record.  
Insurance 
The subjects in the study are covered by the Swedish patient insurances. 
Economy 
The trial is an academic study conceived and conducted by healthcare personnel. The study 
is independent of commercial interests. Study logistics, handling of data and statistical 

 
 
 
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assessment will be financed by the Department of Cardiology, Örebro University Hospital, 
Sweden. The investigators will apply for grants from public funds. 
 
Ethical considerations 
The study will be conducted in accordance with the Declaration of Helsinki. The cold pressor 
test activates the sympathetic nervous system and increases blood pressure and heart rate, 
and there is a slight risk of angina during the test. There are otherwise no known risks or 
complications associated with the quantitative sensory testing but it may cause some 
temporary mild to moderate discomfort.  
The patient is free to stop the testing at any time, and in case of angina the testing will be 
stopped and the patient will be closely monitored and administered sublingual nitroglycerin. 
Risks, side effects, advantages and disadvantages in participation 
Subjects will be treated according to standard clinical practice. There is a slight risk of the 
test causing angina chest pain. However, we do not expect that subjects will have any 
disadvantages from participating in the study. The risk of complications during quantitative 
sensory testing is considered low. 
Guidelines for obtaining informed consent 
Subjects will enter the study after signing the informed consent form. Candidate participants 
will receive written information of the study, and oral information by a physician 
participating in the study. The subjects will be given time to think through participation in 
the study and to ask questions. Informed consent will be obtained by a Good Clinical Practice 
qualified physician participating in the study. 
Withdrawal 

 
 
 
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A subject can withdraw from the study at any time. Data collected up to the end of follow-up 
will be used in the final analysis of the study. 
 
Publication 
Results, positive as well as negative or inconclusive, will be published in an international 
medical journal, primarily in a cardiology journal. 
 
End of trial and archiving 
The study will end when the last subject has signed informed consent, completed the 
questionnaires and has undergone clinical examination and quantitative sensory testing. The 
steering committee reserves the right to terminate the study prematurely e.g. if the study 
participant recruitment is too slow, if study participant retention in the study is insufficient 
or if undue risk related to the quantitative sensory testing arises. Data collected during the 
study will be archived for at least 10 years after the study has been completed. 
 
 
 

 
 
 
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References 
1. 
Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology of atrial fibrillation: 
European perspective. (1179-1349 (Print)). 
2. 
Bjorck S, Palaszewski B Fau - Friberg L, Friberg L Fau - Bergfeldt L, Bergfeldt L. Atrial 
fibrillation, stroke risk, and warfarin therapy revisited: a population-based study. (1524-4628 
(Electronic)). 
3. 
Haim M, Hoshen M, Reges O, Rabi Y, Balicer R, Leibowitz M. Prospective national study 
of the prevalence, incidence, management and outcome of a large contemporary cohort of patients 
with incident non-valvular atrial fibrillation. (2047-9980 (Electronic)). 
4. 
Benjamin EJ, Wolf Pa Fau - D'Agostino RB, D'Agostino Rb Fau - Silbershatz H, 
Silbershatz H Fau - Kannel WB, Kannel Wb Fau - Levy D, Levy D. Impact of atrial fibrillation on the risk 
of death: the Framingham Heart Study. (0009-7322 (Print)). 
5. 
Stewart S, Hart Cl Fau - Hole DJ, Hole Dj Fau - McMurray JJV, McMurray JJ. A 
population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of 
the Renfrew/Paisley study. (0002-9343 (Print)). 
6. 
Thrall G, Lane D Fau - Carroll D, Carroll D Fau - Lip GYH, Lip GY. Quality of life in 
patients with atrial fibrillation: a systematic review. (1555-7162 (Electronic)). 
7. 
Jacobs V, Cutler MJ, Day JD, Bunch TJ. Atrial fibrillation and dementia. (1873-2615 
(Electronic)). 
8. 
Kirchhof P Fau - Benussi S, Benussi S Fau - Kotecha D, Kotecha D Fau - Ahlsson A, 
Ahlsson A Fau - Atar D, Atar D Fau - Casadei B, Casadei B Fau - Castella M, et al. 2016 ESC Guidelines 
for the management of atrial fibrillation developed in collaboration with EACTS. (1522-9645 
(Electronic)). 
9. 
Savelieva I, Camm AJ. Clinical relevance of silent atrial fibrillation: prevalence, 
prognosis, quality of life, and management. (1383-875X (Print)). 
10. 
Patel N, Chung EH, Mounsey JP, Schwartz JD, Pursell I, Gehi AK. Effectiveness of atrial 
fibrillation monitor characteristics to predict severity of symptoms of atrial fibrillation. (1879-1913 
(Electronic)). 
11. 
Thrall G, Lip Gy Fau - Carroll D, Carroll D Fau - Lane D, Lane D. Depression, anxiety, and 
quality of life in patients with atrial fibrillation. (0012-3692 (Print)). 
12. 
Lip GY, Laroche C, Ioachim PM, Rasmussen LH, Vitali-Serdoz L, Petrescu L, et al. 
Prognosis and treatment of atrial fibrillation patients by European cardiologists: one year follow-up 
of the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-
AF Pilot registry). (1522-9645 (Electronic)). 
13. 
Nabauer M, Gerth A Fau - Limbourg T, Limbourg T Fau - Schneider S, Schneider S Fau - 
Oeff M, Oeff M Fau - Kirchhof P, Kirchhof P Fau - Goette A, et al. The Registry of the German 
Competence NETwork on Atrial Fibrillation: patient characteristics and initial management. (1532-
2092 (Electronic)). 
14. 
Lane DA, Langman Cm Fau - Lip GYH, Lip Gy Fau - Nouwen A, Nouwen A. Illness 
perceptions, affective response, and health-related quality of life in patients with atrial fibrillation. 
(0022-3999 (Print)). 
15. 
Walfridsson UA-Ohoo, Steen Hansen P, Charitakis EA-Ohoo, Almroth H, Jonsson A, 
Karlsson LOA-Ohoo, et al. Gender and age differences in symptoms and health-related quality of life 
in patients with atrial fibrillation referred for catheter ablation. (1540-8159 (Electronic)). 
16. 
Reynolds MR, Lavelle T Fau - Essebag V, Essebag V Fau - Cohen DJ, Cohen Dj Fau - 
Zimetbaum P, Zimetbaum P. Influence of age, sex, and atrial fibrillation recurrence on quality of life 
outcomes in a population of patients with new-onset atrial fibrillation: the Fibrillation Registry 
Assessing Costs, Therapies, Adverse events and Lifestyle (FRACTAL) study. (1097-6744 (Electronic)). 

 
 
 
Date: 
2020-11-24 
Version: 1.2 
 
 
 
17 
17. 
Ballatore A, Matta M, Saglietto A, Desalvo P, Bocchino PP, Gaita F, et al. Subclinical and 
Asymptomatic Atrial Fibrillation: Current Evidence and Unsolved Questions in Clinical Practice. LID - 
E497 [pii] LID - 10.3390/medicina55080497 [doi]. (1648-9144 (Electronic)). 
18. 
Rienstra M, Lubitz Sa Fau - Mahida S, Mahida S Fau - Magnani JW, Magnani Jw Fau - 
Fontes JD, Fontes Jd Fau - Sinner MF, Sinner Mf Fau - Van Gelder IC, et al. Symptoms and functional 
status of patients with atrial fibrillation: state of the art and future research opportunities. (1524-
4539 (Electronic)). 
19. 
Hindricks G, Piorkowski C Fau - Tanner H, Tanner H Fau - Kobza R, Kobza R Fau - Gerds-
Li J-H, Gerds-Li Jh Fau - Carbucicchio C, Carbucicchio C Fau - Kottkamp H, et al. Perception of atrial 
fibrillation before and after radiofrequency catheter ablation: relevance of asymptomatic arrhythmia 
recurrence. (1524-4539 (Electronic)). 
20. 
Frobert O, Arendt-Nielsen L Fau - Bak P, Bak P Fau - Funch-Jensen P, Funch-Jensen P 
Fau - Peder Bagger J, Peder Bagger J. Pain perception and brain evoked potentials in patients with 
angina despite normal coronary angiograms. (1355-6037 (Print)). 
21. 
Arendt-Nielsen L, Nie H Fau - Laursen MB, Laursen Mb Fau - Laursen BS, Laursen Bs 
Fau - Madeleine P, Madeleine P Fau - Simonsen OH, Simonsen Oh Fau - Graven-Nielsen T, et al. 
Sensitization in patients with painful knee osteoarthritis. (1872-6623 (Electronic)). 
22. 
Staud R, Cannon Rc Fau - Mauderli AP, Mauderli Ap Fau - Robinson ME, Robinson Me 
Fau - Price DD, Price Dd Fau - Vierck CJ, Jr., Vierck CJ, Jr. Temporal summation of pain from 
mechanical stimulation of muscle tissue in normal controls and subjects with fibromyalgia syndrome. 
(0304-3959 (Print)). 
23. 
Sandrini G, Rossi P Fau - Milanov I, Milanov I Fau - Serrao M, Serrao M Fau - Cecchini 
AP, Cecchini Ap Fau - Nappi G, Nappi G. Abnormal modulatory influence of diffuse noxious inhibitory 
controls in migraine and chronic tension-type headache patients. (0333-1024 (Print)). 
24. 
Olesen SS, Brock C Fau - Krarup AL, Krarup Al Fau - Funch-Jensen P, Funch-Jensen P Fau 
- Arendt-Nielsen L, Arendt-Nielsen L Fau - Wilder-Smith OH, Wilder-Smith Oh Fau - Drewes AM, et al. 
Descending inhibitory pain modulation is impaired in patients with chronic pancreatitis. (1542-7714 
(Electronic)). 
25. 
Arendt-Nielsen L, Morlion B, Perrot S, Dahan A, Dickenson A, Kress HG, et al. 
Assessment and manifestation of central sensitisation across different chronic pain conditions. 
(1532-2149 (Electronic)). 
26. 
Puntillo K, Neighbor M Fau - O'Neil N, O'Neil N Fau - Nixon R, Nixon R. Accuracy of 
emergency nurses in assessment of patients' pain. (1524-9042 (Print)). 
27. 
Bergmann N, Ballegaard S Fau - Holmager P, Holmager P Fau - Kristiansen J, Kristiansen 
J Fau - Gyntelberg F, Gyntelberg F Fau - Andersen LJ, Andersen Lj Fau - Hjalmarson A, et al. Pressure 
pain sensitivity: a new method of stress measurement in patients with ischemic heart disease. (1502-
7686 (Electronic)). 
28. 
Richebe P Fau - Rivat C, Rivat C Fau - Cahana A, Cahana A. Stress-induced hyperalgesia: 
any clinical relevance for the anesthesiologist? (1528-1175 (Electronic)). 
29. 
Harden M, Nystrom B Fau - Kulich K, Kulich K Fau - Carlsson J, Carlsson J Fau - Bengtson 
A, Bengtson A Fau - Edvardsson N, Edvardsson N. Validity and reliability of a new, short symptom 
rating scale in patients with persistent atrial fibrillation. (1477-7525 (Electronic)). 
30. 
Harden M, Nystrom B Fau - Bengtson A, Bengtson A Fau - Medin J, Medin J Fau - Frison 
L, Frison L Fau - Edvardsson N, Edvardsson N. Responsiveness of AF6, a new, short, validated, atrial 
fibrillation-specific questionnaire--symptomatic benefit of direct current cardioversion. (1572-8595 
(Electronic)). 
31. 
Wynn GJ, Todd DM, Webber M, Bonnett L, McShane J, Kirchhof P, et al. The European 
Heart Rhythm Association symptom classification for atrial fibrillation: validation and improvement 
through a simple modification. (1532-2092 (Electronic)). 

 
 
 
Date: 
2020-11-24 
Version: 1.2 
 
 
 
18 
32. 
McHorney CA, Ware Je Jr Fau - Lu JF, Lu Jf Fau - Sherbourne CD, Sherbourne CD. The 
MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and 
reliability across diverse patient groups. (0025-7079 (Print)). 
33. 
Petersen KK, Arendt-Nielsen L Fau - Simonsen O, Simonsen O Fau - Wilder-Smith O, 
Wilder-Smith O Fau - Laursen MB, Laursen MB. Presurgical assessment of temporal summation of 
pain predicts the development of chronic postoperative pain 12 months after total knee 
replacement. (1872-6623 (Electronic)). 
34. 
Neogi T, Guermazi A, Roemer F, Nevitt MC, Scholz J, Arendt-Nielsen L, et al. 
Association of Joint Inflammation With Pain Sensitization in Knee Osteoarthritis: The Multicenter 
Osteoarthritis Study. (2326-5205 (Electronic)). 
35. 
Neogi T, Frey-Law L, Scholz J, Niu J, Arendt-Nielsen L, Woolf C, et al. Sensitivity and 
sensitisation in relation to pain severity in knee osteoarthritis: trait or state? (1468-2060 (Electronic)).