ACCORDING TO PREVIOUS research, 55% to 94% of

ORIGINAL ARTICLE Pain Physiology Education Improves Pain Beliefs in Patients With Chronic Fatigue Syndrome Compared With Pacing and Self-Management Education: A Double-Blind Randomized Controlled Trial Mira Meeus, PhD, Jo Nijs, PhD, Jessica Van Oosterwijck, PT, Veerle Van Alsenoy, PT, Steven Truijen, PhD 1153 ABSTRACT. Meeus M, Nijs J, Van Oosterwijck J, Van Alsenoy V, Truijen S. Pain physiology education improves pain beliefs in patients with chronic fatigue syndrome compared with pacing and self-management education: a double-blind randomized controlled trial. Arch Phys Med Rehabil 2010;91:1153-9. Objective: To examine whether pain physiology education was capable of changing pain cognitions and pain thresholds in patients with chronic fatigue syndrome (CFS) and chronic widespread pain. Design: Double-blind randomized controlled trial. Setting: Specialized chronic fatigue clinic in university hospital. Participants: A random sample of patients (N 48) with CFS patients (8 men, 40 women) experiencing chronic pain, randomly allocated to the control group (n 24) or experimental group (n 24). Two women in the experimental group did not complete the study because of practical issues (lack of time and restricted mobility). Interventions: One individual pain physiology education session (experimental) or 1 pacing and self-management education session (control). Main Outcome Measures: Algometry, the Neurophysiology of Pain Test, and questionnaires evaluating pain cognitions the Pain Coping Inventory, the Pain Catastrophizing Scale, and the Tampa Scale for Kinesiophobia version CFS were completed immediately before and immediately after the intervention. From the Division of Musculoskeletal Physiotherapy, Department of Health Sciences, Artesis University College, Antwerp (Meeus, Nijs, Van Oosterwijck, Van Alsenoy, Truijen); Department of Human Physiology, Faculty of Physical Education and Physiotherapy, Vrije Universiteit (Meeus, Nijs, Van Oosterwijck), Department of Rehabilitation and Physiotherapy, University Hospital (Nijs, Van Oosterwijck), Brussels, Belgium. Presented to the World Confederation of Physical Therapy, June 2 6, 2007, Vancouver, Canada; the International Council on Physiotherapy in Psychiatry and Mental Health, February 27 29, 2008, Bergen University, Norway; the European Society of Physical and Rehabilitation Medicine, June 3 6, 2008, Bruges, Belgium; the International Federation of Orthopaedic Manipulative Therapists, June 9 13, 2008, Rotterdam, The Netherlands; and the European Federation of International Association for the Study of Pain Chapters, September 8 12, 2009, Lisbon, Portugal. Supported by the Higher Institute of Physiotherapy, Department of Health Sciences, Artesis University College Antwerp, Belgium (grant no. G 807), the Faculty of Physical Education and Physiotherapy Vrije Universiteit Brussel, Brussels, Belgium (OZR project OZ.R. 1234/MFYS Wer2), and a postdoctoral research fellowship of the Research Foundation Flanders Fonds Wetenschappelijk Onderzoek (FWO). No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Reprint requests to Jo Nijs, PhD, Artesis Hogeschool Antwerpen, Dept of Health Sciences, Division of Musculoskeletal Physiotherapy, Van Aertselaerstraat 31, 2170 Merksem, Belgium, e-mail: jo.nijs@artesis.be or jo.nijs@vub.ac.be. 0003-9993/10/9108-00054$36.00/0 doi:10.1016/j.apmr.2010.04.020 Results: After the intervention, the experimental group demonstrated a significantly better understanding of the neurophysiology of pain (P.001) and a reduction of the Pain Catastrophizing Scale subscale ruminating (P.009) compared with controls. For these variables, moderate to large Cohen d effect sizes were revealed (.79 2.53). Conclusions: A 30-minute educational session on pain physiology imparts a better understanding of pain and brings about less rumination in the short term. Pain physiology education can be an important therapeutic modality in the approach of patients with CFS and chronic pain, given the clinical relevance of inappropriate pain cognitions. Key Words: Fatigue syndrome; chronic; Patient education as topic; Pain threshold; Questionnaires; Rehabilitation. 2010 by the American Congress of Rehabilitation Medicine ACCORDING TO PREVIOUS research, 55% to 94% of patients with CFS experience chronic musculoskeletal pain. 1-3 Many of these patients have pain without knowing the source. Patients who have no understanding of the mechanisms associated with pain typically consider pain more threatening than those who do, resulting in lower pain tolerance, more catastrophic thoughts, and less adaptive coping strategies. 4 Indeed, patients with CFS and pain frequently report catastrophic thoughts, 5 kinesiophobia, 6,7 and maladaptive coping strategies. 8,9 Catastrophizing is able to predict up to 41% of the variance in pain intensity in patients with CFS. 10 Particularly, helplessness and rumination of the Pain Catastrophizing Scale are strongly related to pain. 10 This may be the result of poor understanding of chronic pain. In addition, these pain cognitions are often important therapy barriers. Especially in the physical therapy practice, where active cooperation of the patient is required, these maladaptive thoughts and cognitions may diminish therapy adherence and efficacy. As described by Smeets et al, 11 psychologic variables are widely known to be important outcome predictors (characteristics that predict outcome independently of therapy), but they may also act as therapy effect modifiers (characteristics that predict treatment effects). 12 Given the fact that information is determining for the appraisal of pain 4 and for therapy efficacy and adherence, explaining the concept of pain to patients may offer a solution. CFS CLBP PCI PCS List of Abbreviations chronic fatigue syndrome chronic low back pain Pain Coping Inventory Pain Catastrophizing Scale

1154 PAIN PHYSIOLOGY EDUCATION IN CHRONIC FATIGUE SYNDROME, Meeus Pain physiology education causes cognitive changes in CLBP patients, namely decreased catastrophizing, which is directly related to better physical performance. 13,14 The effect on pain thresholds has not yet been assessed. However, in the longer term, the shift in pain cognitions may accompany the increase in pain thresholds, given the close link between cognitions and pain. 15 Furthermore, in patients with CFS, the literature does not provide any evidence at all on pain physiology education. Considering the relevance of chronic pain and the frequently observed unhelpful pain cognitions in patients with CFS, pain physiology education might be indicated and deserves further investigation, especially because patients with CFS typically present with concentration and memory problems, possibly precluding understanding of the pain neurophysiology. Therefore, the present study aimed at evaluating the immediate effects of a single pain physiology education session in patients with CFS with chronic pain compared with a pacing and self-management education session on (1) their understanding of pain neurophysiology, (2) the degree of catastrophizing, (3) the degree of kinesiophobia, (4) coping styles, and (5) pain thresholds. We hypothesized that pain physiology education would alter pain cognitions by reconceptualizing the concept of pain. This may be an important new step in the therapeutic process because patients are often in the dark regarding their chronic pain, leading to inappropriate cognitions and behavior and consequently more pain, and interfering with their therapy. METHODS Design An information leaflet was handed to patients intending to participate. When patients agreed to participate, they were asked to sign the informed consent form. The study protocol was approved by the ethical committee of the University Hospital Brussels. Patients were randomly allocated to the experimental or the control group. Both the experimental (pain physiology) and the control (pacing and self-management) education involved one 30-minute 1-on-1 interactive information session. Immediately before and immediately after the intervention, patients completed a battery of questionnaires and underwent algometry or pain threshold testing. Participants Patients were randomly selected from the medical files available at our university-based chronic fatigue clinic in Brussels, Belgium. All patients fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS. 16 To fulfill the Centers for Disease Control and Prevention criteria for CFS, a clinically evaluated, unexplained, persistent, or relapsing chronic fatigue that is of new or definite onset should result in a substantial reduction in previous levels of occupational, educational, social, or personal activities. Furthermore, at least 4 of the following symptoms must have persisted or recurred during 6 or more consecutive months and must not have predated the fatigue: impairment in short-term memory or concentration, tender cervical or axillary lymph nodes, muscle pain, multijoint pain, headache, unrefreshing sleep, and postexertional malaise greater than 24 hours. Any active medical condition, which may explain the presence of chronic fatigue, prohibits the diagnosis of CFS. 16 Therefore, all participants underwent an extensive medical evaluation by the same physician specializing in internal medicine prior to study participation. Besides fulfilling the criteria of CFS, patients had chronic widespread pain, namely pain located axially, on the left and the right side of the body and above and below the waist, lasting for more than 3 months. 17 Only Dutch-speaking patients age 18 to 65 years qualified for the present study. All pain-related treatment and antidepressants with analgesic effects were withdrawn 48 hours before testing, and participants were asked not to undertake physical exertion in the 24 hours prior to the investigation. The use of antidepressants and analgesics was recorded in those who were not compliant with the withdrawal request. An a priori power analysis (power above 0.8; P.01), based on the study results of the Neurophysiology of Pain Test in the study of Moseley, 18 indicated we should aim at including approximately 20 patients a group. Randomization and Allocation Concealment This study was a double-blind randomized controlled experiment in which patients with CFS were randomly allocated to the experimental group and to a control group by lottery. Patients drew numbered lots that were marked either 1 (control group) or 2 (experimental group) from a bag. Neither the patient nor the second researcher performing the assessments was informed about the allocation. This means that patients were aware of participating in an experiment in which 2 information sessions were compared and that the drawn lot determined the allocation, but the design and the interventions were not explained in terms of control or experimental groups. Only the first researcher providing the education sessions was aware of the allocation but was not involved in the assessment process, and there was no communication between the 2 researchers (teacher and assessor). Intervention Pain physiology education covered the physiology of the nervous system in general and of the pain system in particular. The theoretic information was illustrated with pictures and examples. Information for this session was taken from the book Explain Pain 19 and is discussed in detail elsewhere. 13,14,18,20 The objective of the education was to teach patients the function, mechanisms, and modulation of (chronic) pain, and so forth. 19 These topics were discussed with every participant and were the basis for a further individualized interactive education session, adopted on particular life situations of the patient. Pacing and self-management education was provided to all participants in the control group. Pacing is a strategy in which patients are encouraged to achieve an appropriate balance between activity and rest in order to avoid exacerbation and to set realistic goals for increasing activity. 21,22 Following this energy management strategy, patients should avoid activities at an intensity that exacerbates symptoms, or they should intersperse activities with periods of rest. 21,22 Outcome Measures The primary study outcome was the Neurophysiology of Pain Test (patient version). This questionnaire assesses the knowledge of pain neurophysiology with 19 theoretic statements concerning nociception and the modulation of nociception, for example: Worse injuries always result in worse pain. Patients were asked to read the statements and to answer with true, false, or undecided. The correct answers were summed, with a maximum score of 19/19. When all answers were wrong, patients scored 0/19. In the patient version of the test, the medical jargon was simplified for easier interpretation. The construction of the test is explained by Moseley. 18 In a previous study, we translated the English test into Dutch and

PAIN PHYSIOLOGY EDUCATION IN CHRONIC FATIGUE SYNDROME, Meeus 1155 found the questionnaire to be valid and test-retest reliable in patients with CFS with chronic widespread pain. 23 The secondary study outcomes were the questionnaires assessing pain cognition and the algometry. The PCI contains 33 items assessing 6 specific pain-coping strategies that represent 2 higher-order pain coping dimensions: maladaptive (worrying, retreating, resting) and adaptive (transformation, distraction, reducing demands) coping. 24 Patients were asked to rate on a 4-point Likert scale ranging from 1 (hardly ever) to 4 (very often) the frequency with which these strategies were used. Results of the different subscales were obtained by taking the mean score of the items belonging to that subscale. A higher score indicated a more frequent application of that specific coping strategy. The PCI has been found to be sufficiently sensitive and valid. 25 The Dutch PCS is a self-reported questionnaire aiming at assessing pain catastrophizing. It consists of 13 items describing different thoughts and feelings that patients may experience when they are experiencing pain. Items are scored on a 5-point scale, and total scores are counted by summing all individual item scores. Higher scores correspond to more severe catastrophic thoughts about pain. Given the evidence for good psychometric quality of the Dutch PCS, 26,27 it was considered to be an appropriate instrument for the present investigation. The Tampa Scale for Kinesiophobia version CFS aims at monitoring kinesiophobia in patients with CFS. 6 It is a modification of the original Tampa Scale for Kinesiophobia to make the questionnaire more appropriate for patients with CFS by replacing the word pain by symptoms. Each of the items on the questionnaire is provided with a 4-point Likert scale, with scoring alternatives ranging from strongly agree to strongly disagree. A total score is calculated (1 4 for each item) after inversion of the individual scores of items 4, 8, 12, and 16. A total score greater than 37 indicates high fear of movement. 7,28 Evidence for the internal consistency and the convergent and congruent validity of scores obtained by the Dutch Tampa Scale for Kinesiophobia version CFS has previously been reported by Nijs et al. 6 Pressure pain thresholds were measured with an analog Fisher algometer a with a rubber tip of 1cm 2 in the skin web between thumb and index finger, 29 5cm lateral to the spinous process of L3, 30 and at the proximal third of the calf, in order to test pain thresholds on nonspecific locations both on the extremities and the trunk. All these sites were assessed in random order. The force is gradually increased at a rate of 1kg/s until the subject indicates that the pain level has been reached. The threshold is determined as the mean of the 2 last values out of 3 consecutive (10s in between) measurements, because this procedure has found to be reliable in healthy controls. 31 Pressure algometry has been found to be efficient and reliable in the exploration of physiopathological mechanisms involved in pain 32,33 and is useful for the evaluation of treatment outcome, as reviewed by Fischer. 34 Analysis All data were analyzed using the Statistical Package for Social Sciences 12.0 for Windows. b We tested normality of the variables with the Kolmogorov-Smirnov test and calculated appropriate descriptive statistics. Two-factor repeated-measures analyses of variance (group time) were used to identify a treatment effect on the dependent variables. Pain thresholds and the results of the PCS, PCI, Tampa Scale for Kinesiophobia version CFS, and Neurophysiology of Pain Test were the dependent variables. Given the large number of outcome measures, the significance level was set at.01. In order to account for missing data, we used the last observation carried forward method for intention-to-treat analysis. We calculated effect sizes as Cohen d, with d defined as the difference between the 2 means divided by the pooled SD for those means. A d value of.20 is described as small,.50 as medium (moderate), and.80 as large. 35 RESULTS This study consisted of 48 patients with CFS, 8 men (16.7%) and 40 women (83.3%), who were randomly allocated to either an experimental group or a control group. In the experimental group, 2 women did not complete the study. One was pressed for time, and the other woman was not able to lie on her stomach (for pain threshold assessment of the calf and back) because of restricted mobility. The flow of participants through the study is presented in figure 1. Group characteristics are shown in table 1. As presented in table 2 and figure 2, we found significant differences in the primary outcome measure, the pain neurophysiology knowledge (P.001), in the experimental group compared with the control group. According to figure 2A, it is clear that the control group maintained similar scores, while the understanding of the experimental group increased significantly. Regarding the secondary outcome measures, the tendency to ruminate (PCS; P.009) decreased significantly in the pain physiology education group compared with the control group. Figure 2B clearly shows constant values for the control group, whereas the experimental group presents a decrease. Trends toward significance decreases were revealed for the tendency to use the adaptive coping strategy distraction (P.021) and worrying (P.011), as presented in figure 2C and D. While pain threshold values decreased in both groups over time, these differences were not significantly different between groups at the end of the intervention (see table 2). All prevalues and postvalues are presented in table 2, along with the respective Cohen d effect sizes for each group. An intention-to-treat-analysis (last observation carried forward) was executed, but this did not affect the findings (data not shown). DISCUSSION After a 30-minute educational session on pain physiology, patients presented an increased understanding of pain and reported the intention to ruminate less compared with a control group. Primary Outcome Measure Patients with CFS are able to understand the neurophysiology of pain. It was already shown that CLBP patients understood the matter. 18 However, because numerous patients with CFS struggle with concentration and memory problems, 16 comprehension was not guaranteed. Clearly, patients with CFS are indeed able to increase their understanding of the neurophysiology of pain. The experimental group showed an increase in knowledge immediately afterward, resulting in a large d value of 2.53. This means that the average person of the pain physiology education group would score better than 99% of the control group after the intervention. Secondary Outcome Measures Second, the experimental group reported their intention to ruminate significantly less on the PCS. The intention to use more adaptive coping strategies in the future, such as looking for distraction, as opposed to less maladaptive coping styles, such as worrying, nearly reached significance. A type II error

1156 PAIN PHYSIOLOGY EDUCATION IN CHRONIC FATIGUE SYNDROME, Meeus Fig 1. Overview of the study design. may have occurred because of lack of statistical power in the present study (varying between.40 and.50 for pain cognitions). This can be determined by a larger study. The present results are comparable to the previous randomized clinical trials in CLBP patients, 14 in which patients received a 3-hour pain physiology education session 13 and a workbook for 2 weeks. 14 These findings are important because these short sessions are easier to implement in the clinical approach toward patients with CFS. Changes in cognitions are important to achieve because they are known to be closely linked to disability and pain (see review 36) ). Pain cognitions are indeed able to influence pain perception via modulation of the descending pathways, sensitizing the spinal dorsal horn (see review 15 ). In addition, catastrophizing appeared related to exercise capacity in patients with CFS. 10 In consequence, decreased catastrophizing may result in increased exercise capacity and activity levels, which may be responsible for improved physical performance, 37 leading to increased pain thresholds and pain tolerance in the longer term. Although pressure pain thresholds increased in the pain physiology education groups, it is not a matter of a specific therapy effect, because they also increased in the control group. An alteration in catastrophic thinking may cause an alteration in somatic vigilance, 13 possibly leading to a change in pain thresholds/tolerance, 38 but the assessment in the present study was probably too soon after the intervention to obtain these therapy-related effects. Given the close link between cata-

PAIN PHYSIOLOGY EDUCATION IN CHRONIC FATIGUE SYNDROME, Meeus 1157 Variable Table 1: Demographic Information Experimental Group (n 24) Control Group (n 24) Sex (M, F), n 2, 22 6, 18 Age (mean years SD) 38.3 10.6 42.3 10.2 Analgesics (n) 2 8 AD (n) 9 7 NOTE. Antidepressants and analgesics refer to how many participants used the substances on the test day. Age was compared with an independent t test, other variables with a Fisher exact test. Abbreviations: AD, antidepressants; F, female; M, male. strophizing and pain in CFS, 10 it is not unlikely that decreased catastrophizing would alter pain thresholds or tolerance in the longer term. Until now, an effect on pain was found only after a 4-week physical therapy program including pain physiology education, manual therapy, and specific exercises in CLBP patients. 20 It may be clear that pain physiology education is a useful therapeutic modality because pain cognitions are related to pain intensity and can result in important therapy barriers. By starting with pain physiology education before applying more active modalities, dysfunctional beliefs could be alleviated. Physical therapists often are at a loss with what to do with patients with CFS because of the low exercise tolerance and postexertional malaise typically seen in patients with CFS, 16,39,40 resulting in low therapy adherence and efficacy. By reconceptualizing pain, somatic vigilance may decrease and pain thresholds/ tolerance, and in consequence, physical performance could increase. This way, patients may be more responsive to further physical therapy strategies. 14 Study Limitations An important consideration is whether the information given during the pain physiology educational sessions and any changes made are retained by the patient for future reference. Patients had not yet had time to digest the material. On the other hand, forgetting curves usually show a steep decline in retention shortly after initial learning and a more gradual drop over long periods. In addition, the present study design allowed us to evaluate only their future intentions concerning pain cognitions and behavior and not their actual beliefs or behavior a certain time after the intervention. This is in fact the most important limitation of the present study: the lack of a follow-up period in which both information retention and changes in cognitions or behavior could be evaluated. Stronger evidence for the use of pain physiology education sessions in patients with CFS with chronic pain could be provided by studying the long-term effects of more intensive education. Education sessions of 3 hours will probably be unfeasible in patients with CFS because of the typical fog in the head, but more short sessions could be organized, eventually in combination with a workbook for thorough comprehension, repetition, and evaluation of the progression. These repetitions and evaluations may be necessary given the fluctuating concentration and memory problems in CFS. Besides the assessment immediately after therapy, a follow-up period could reveal interesting results. A longer intervention period and the follow-up period would allow patients to apply or to act on what Variable Table 2: Prevalues and Postvalues With Cohen d Effect Sizes Group Before Mean SD After Mean SD Absolute Difference Cohen d Neurophysiology Pain Test CON 5.21 3.43 5.46 3.79 0.25 2.53* EXP 6.50 2.95 13.75 1.70 7.25 PCI transforming CON 2.23 0.80 2.09 0.62 0.14 0.07 EXP 2.48 0.71 2.30 0.64 0.18 PCI distraction CON 2.51 0.60 2.41 0.52 0.10 0.69 EXP 2.22 0.54 2.32 0.62 0.10 PCI reducing demands CON 2.71 0.76 2.60 0.85 0.11 0.30 EXP 2.60 0.59 2.29 0.70 0.31 PCI retreating CON 2.53 0.57 2.53 0.57 0.00 0.17 EXP 2.27 0.80 2.21 0.73 0.06 PCI worrying CON 2.09 0.67 2.02 0.67 0.07 0.76 EXP 2.11 0.41 1.85 0.40 0.26 PCI resting CON 2.60 0.64 2.56 0.69 0.04 0.50 EXP 2.41 0.59 2.15 0.59 0.26 PCS helplessness CON 9.96 6.77 9.29 6.93 0.67 0.29 EXP 8.54 5.39 6.63 4.70 1.91 PCS magnification CON 4.00 3.51 3.75 4.19 0.25 0.18 EXP 2.38 1.93 1.67 1.55 0.71 PCS ruminating CON 7.83 4.59 7.67 4.91 0.16 0.79* EXP 7.29 3.86 5.71 3.46 1.58 TSK-CFS CON 39.71 7.15 37.42 8.15 2.29 0.56 EXP 39.17 9.52 33.21 6.58 5.96 Mean PPT (kg/cm 2 ) CON 3.85 1.79 4.11 1.92 0.26 0.06 EXP 3.75 1.22 3.94 1.39 0.19 Abbreviations: CON, control group; EXP, experimental group; PPT, pressure pain threshold; TSK-CFS, Tampa Scale for Kinesiophobia version CFS. *I ndicates effect sizes of variables for which a significant difference was observed or indicates effect sizes of variables for which a trend toward a significant difference was observed. Transformed percentiles indicate percentage of control group who would score/be below the average person in experimental group.

1158 PAIN PHYSIOLOGY EDUCATION IN CHRONIC FATIGUE SYNDROME, Meeus Fig 2. Effects of interventions on pain neurophysiology knowledge, catastrophizing and coping. X-axis, present before and after intervention; Y-axis, scores on the different questionnaires. P values are the significance levels for the differences in change between the 2 groups (interaction). they learned. Then a real change in behavior could be observed. In addition, pain physiology education is not a stand-alone therapy and could be combined with other modalities. Consequently, the next step is to assess multimodal treatments including pain physiology education and their long-term clinical effects. A last issue is the fact that we found significant changes, translated in Cohen effect sizes, but up to now the clinical relevance of, for instance, a drop of 1.58 on the PCS subscale ruminating remains undefined. Finally, prudence is called for in extrapolating the results given the fact that the effects of education are dependent on the format, the content, the patient, and also the practitioner providing the education. The attitude of the health care provider is crucial in educating patients. 41 Furthermore, different kinds or formats of pain physiology education could be tested. For example, 1-on-1 sessions are time-consuming, but compared with group session in CLBP patients, a little more effective. 18 CONCLUSIONS We can conclude that patients with CFS are indeed able to increase their understanding of the neurophysiology of pain, because they scored much better on the Neurophysiology Pain Test after the pain physiology education. The pain physiology education has even immediate effects on ruminating (part of catastrophizing) about the pain. No therapy effect could be revealed for the pain thresholds. Pain physiology education can be seen as an efficient component of the biopsychosocial approach to chronic pain in CFS, but further work is required to confirm and extend these promising results. Acknowledgments: We are grateful to K. De Meirleir, MD, for diagnosing the study participants, to A. Farasyn, PhD, for kindly providing his expertise on pressure pain threshold assessment, and to Karen Wallman, PhD, for editing the article. References 1. Jason LA, Richman JA, Rademaker AW, et al. A communitybased study of chronic fatigue syndrome. Arch Intern Med 1999; 159:2129-37. 2. Nishikai M, Tomomatsu S, Hankins RW, et al. Autoantibodies to a 68/48 kda protein in chronic fatigue syndrome and primary FM: a possible marker for hypersomnia and cognitive disorders. Rheumatology 2001;40:806-10. 3. Nijs J, De Meirleir K, Truijen S. Hypermobility in patients with chronic fatigue syndrome: preliminary observations. J Musculoskelet Pain 2004;12:9-17. 4. Jackson T, Pope L, Nagasaka T, Fritch A, Iezzi T, Chen H. The impact of threatening information about pain on coping and pain tolerance. Br J Health Psychol 2005;10:441-51. 5. Petrie K, Moss-Morris R, Weinman J. The impact of catastrophic beliefs on functioning in chronic fatigue syndrome. J Psychosom Res 1995;39:31-7. 6. Nijs J, De Meirleir K, Duquet W. Kinesiophobia in chronic fatigue syndrome: assessment and associations with disability. Arch Phys Med Rehabil 2004;85:1586-92.

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