 Pain education vs. routine physical therapy in chronic neck pain Eur J Transl Myol 32 (3): 10674, 2022 doi: 10.4081/ejtm.2022.10674 - 1 - A protocol for a randomized trial on pain neuroscience education vs. routine physical therapy in people with chronic neck pain Farzaneh Soleimani (1,2), Hosein Kouhzad Mohamadi (1,2), Maryam Saadat (1,2), Fateme Derisfard (3), Gholamhossein Nassadj (1,2) (1) Musculoskeletal Rehabilitation Research Center Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; (2) Department of Physiotherapy, School of Rehabilitation Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; (3) Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (CC BY-NC 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. Abstract The aim of this study is to investigate the effects of combining routine physical therapy with pain neuroscience education (PNE) on psychosocial factors, physical performance, and the experienced pain in patients with chronic neck pain (CNP). This study is a double-blind randomized clinical trial in which patients will be randomly allocated to two groups, routine physical therapy with and without PNE. Patients will be assessed at the baseline, post intervention, and three months later. The results of this research will be used to establish effectiveness of treatment strategies for CNP. Due to the rigorous scientific methods used in this research, the suggested interventions would be clinically applicable in the health care systems. Key Words: Chronic neck pain; pain neuroscience education; psychosocial factors; physical therapy. Eur J Transl Myol 32 (3): 10674, 2022 doi: 10.4081/ejtm.2022.10674 Neck pain is a major public health worldwide which interferes with daily life and can lead to depression and anxiety.1 The majority of the neck pain disorders are often non- specific in nature, meaning that there is either no tissue damage or the tissue damage is not severe enough to explain the associated symptoms.2 Central sensitization (CS)3 is a physiological process in chronic pain patients that results in an increase in the responsiveness of pain neurons in the central nervous system to the entry of natural or sub-threshold afferents.4 However, if CS persists, it becomes maladaptive and can facilitate the maintenance of symptoms such as pain in the absence of tissue damage or illness. If this occurs, CS can be viewed as a pathophysiological process, which negatively impacts treatment outcome. In this view, it seems rational to consider treating CS.5,6 Chronic neck pain (CNP) is one of the conditions in which CS was seen in a subgroup of patients. A study by Roldan-Jimenez et al. (2020)7 confirmed CS in 33% of patients with CNP. In recent evidence, a therapeutic approach, named pain neuroscience education (PNE) has been recommended in care for individuals with chronic musculoskeletal conditions.8-10 PNE consists of educational sessions describing the neurobiology and neurophysiology of chronic pain and pain processing. Some researchers have reported the possibility of improving the effects of treatment with PNE in patients with chronic musculoskeletal pain. For example, one study has shown that 2 sessions of PNE improve pain in fibromyalgia patients.8 Meeus et al. also showed that Pain physiology education has been able to change the perception of pain, such as pain catastrophe in chronic musculoskeletal pain.9,10 As far as we know, there is little evidence examining the role of combining PNE with routine physical therapy for CNP versus simple routine physical therapy. Therefore, the purpose of this study is to compare the effectiveness of combining PNE with routine physical therapy for CNP with routine physical therapy alone. We hypothesized that PNE could lead to improvement in psychosocial measures, functionality and pain in patients with CNP. Pain education vs. routine physical therapy in chronic neck pain Eur J Transl Myol 32 (3): 10674, 2022 doi: 10.4081/ejtm.2022.10674 - 2 - Materials and Methods Study Design This proposed study is a double-blind, parallel-group, randomized control. This study protocol report follows the recommendations of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline.11 In addition, specific interventions were described based on the Template for Intervention Description and Replication (TIDieR) checklist,12 and the Consensus on Exercise Reporting Template (CERT) checklist.13 The trial has been approved by the ethics committee of Ahvaz Jundishapur University of medical sciences (Ethical number: IR.AJUMS.REC.1400.098). The trial identifier code is IRCT20210607051508N1 and it was registered on June 21, 2021. Participants and Setting Patients will be recruited from the physical therapy clinics located in Ahvaz, Iran. The participants will be included according to the following inclusion criteria: age from 18 to 65,14 diagnosis of nonspecific neck pain [pain in cervical region that provokes by sustained neck postures or particular neck movements with no specific pathological finding],15 history of pain greater than twelve weeks, ability to comprehend, speak, and write in Persian, not being under any other treatments up to 6 months prior to the study, visual analog scale (VAS) at least 30 out of 100, the Central Sensitization Inventory (CSI) score of above 40. The exclusion criteria are a history of malignancies, fractures, metabolic, rheumatism, cardiovascular, or neurologic disorders, neck pain due to radiculopathy, myelopathy, accompanied by headache, patients with generalized pain disorders such as fibromyalgia and chronic fatigue syndrome.16,17 Sample Size The sample size was calculated using the G power software, version 3.1.10. Applying a significance level of 0.05, effect size of 0.8, and a power of 80%, the calculation revealed that 22 patients would be required in each group. Since a 10% patients loss due to follow- up is presumed, a total of 25 patients will be included in each group. Randomization and allocation concealment Individuals who met the inclusion criteria will randomly be allocated to one of two treatment arms: (1) routine physical therapy plus PNE or (2) Routine physical therapy, using computer-generated random numbers in stratified permuted block (block size of 4 and 6). The allocation will be concealed in an opaque, sealed envelope. A research assistant opens them and assigns patients to either of the treatment arms. The randomization will be conducted after signing the informed consent and baseline assessments. Demographic measures include gender, age, height, weight, and comorbidities. Interventions The recruitment is announced for patients with nonspecific CNP from public physical therapy clinics, and the screening will be based on the predefined inclusion and exclusion criteria. The participants will be evaluated before, after the intervention, and three months later. Treatment will be performed by one expert physical therapist. Both intervention groups will receive 12 sessions, 3 times a week. Routine physical therapy group: All subjects received the routine exercise program consist of 20 minutes TENS (Novin, model 733x), hot packs, stretching of pectoralis minor, pectoralis major, latissimus dorsi, upper trapezius and scalene muscles, deep neck flexor muscle training by a stabilizer instrument, strengthening exercises (using Thera-Band and Dumbbells for deep neck extensors and scapular stabilizer muscles). Routine plus PNE physical therapy group: PNE will be conducted in four consecutive sessions, held in four separate meetings. The first session will be dedicated to elaborating the physiology of pain, the concepts of neurons, synapses, and neural facilitation and inhibitions. Also, the nature of acute versus chronic pain and the concept of neural plasticity will be presented. At the end of the first session, patients will be provided with a booklet elaborating on this information. The second session will be dedicated to teaching the neurophysiology of pain and cortical mechanisms in pain modulation. The educator in this session will attempt to walk the patients through the neuroscience of pain and change their preconceived notions in this regard. Reading assignments are considered to be fulfilled between the first and second sessions alongside practical tasks designed based on appropriate target goals. The third and fourth meeting is dedicated to cognition targeted exercise therapy. At the third session, patients will be instructed to cognition targeted motor control training. In this session, it will be clarified for the patients that the essential objective of this training is cognitive reeducation and the instructed exercises are not directly in favor of reducing their pain. This goal will be attained using an appropriate interview with the patient. Ten exercises will be assigned in each session with 10 seconds breaks between the sessions, and the exercises will initiate from those provoking less avoidance and will proceed to those with stronger avoidance. Eventually, the last session is dedicated to cognition-targeted dynamic and functional exercises, consisting of time contingent neuromuscular training rather than symptom-oriented training. Gradual exposure will be applied in all training to avoid potential hazards. Motor imaging techniques will be instructed and required before each task, and functional interaction between the trainer and trainee is mandatory for full filling this step. The objective in this last step is Pain education vs. routine physical therapy in chronic neck pain Eur J Transl Myol 32 (3): 10674, 2022 doi: 10.4081/ejtm.2022.10674 - 3 - to gradually transit from static skills to dynamic and eventually functional skills.17 Assessments and Blinding The outcome assessments will be performed by a physical therapist who is blinded toward treatment allocation. Additionally, patients will be blinded toward treatment groups. Outcomes Outcome measurements will be assessed in a random order at baseline, post interventions, and three months after the intervention (Figure 1 and Figure 2). Visual Analogue Scale (VAS) Neck pain intensity will be measured using a 100 mm visual analogue scale where 0 represented ‘no pain’ and 100 the ‘worst pain imaginable’. Participants draw a mark at a point on the line that best reflects the pain they are experiencing at the time of measurement. Higher scores indicate higher pain levels.18 The sensitivity and specificity of this questionnaire and the acceptability of its psychometric properties have been previously approved.19,20 Pressure Pain Threshold (PPT) An algometer (LUTRON Force Gauge 5020, Taiwan) will be used to measure pressure pain thresholds at both the right and left upper trapezius (mid distance between the posterior angle of the acromion and C7), the web space and distal of quadriceps muscles (4 cm above patellar, in supine position).21,22 The PPT on the upper trapezius will be measured with the patient comfortably Fig 1. Flow diagram Pain education vs. routine physical therapy in chronic neck pain Eur J Transl Myol 32 (3): 10674, 2022 doi: 10.4081/ejtm.2022.10674 - 4 - seated in an armless chair. Three measurements will be taken at each point.23 A 30 second resting period will be allowed between measurements.24 Measurement procedures are in line with previous studies. Pressure pain threshold measurements have good intra- (ICC=0.86) and inter rater (ICC=0.76) reliability.25,26 Central Sensitization Inventory (CSI) The CSI questionnaire will be used for the assessment of the central sensitization in patients with CNP,27 which assesses the 25 chronic pain-related symptoms using a Likert scale. Where scoring one indicates that this symptom never occurs, and score five indicates that the targeted symptom always occurs. This questionnaire is routinely used to identify the related symptoms to central sensitivity and quantify them and provides acceptable reliability and dimensionality.27-31 The Neurophysiology of Pain Questionnaire This questionnaire is used to assess patients’ conceptualization of the biological mechanisms that underpin pain.10,32,33 It has 19 questions and one point is allocated for each correctly answered question, up to a maximum of 19 points..The neurophysiology of pain Fig 2. SPIRIT figure showing the schedule of enrollment, interventions, and assessments STUDY PERIOD Enrolment Allocation Post-allocation Close-out TIMEPOINT** -t1 0 t0 t post intervention t3 Months ENROLMENT: Eligibility screen X Informed consent X Allocation X INTERVENTIONS: [Pain Neuroscience Education + Routine Physiotherapy for Chronic Neck Pain] [Routine Physiotherapy for Chronic Neck Pain] ASSESSMENTS: [Visual Analogue Scale] X X X [Pressure Pain Threshold] X X X [Central Sensitization Inventory] X X X [Neck Disability Index] X X X [Pain Catastrophizing Scale] X X X [Tampa Scale of Kinesiophobia] X X X [Pain Vigilance and Awareness Questionnaire] X X X [Brief Illness Perception Questionnaire] X X X [Short Form Health Survey] X X X Pain education vs. routine physical therapy in chronic neck pain Eur J Transl Myol 32 (3): 10674, 2022 doi: 10.4081/ejtm.2022.10674 - 5 - questionnaire has demonstrated good internal consistency (Cronbach α=0.91) Physical Performance-related Measures The neck disability index (NDI) questionnaire will be used for assessing the disability due to neck pain. It has excellent reliability and good convergent validity and responsiveness.34,35 Psychosocial Measures Pain catastrophizing scale (PCS) The 13-item Pain Catastrophizing Scale will be used to measure participants’ tendency to magnify the threat value of a pain stimulus. The total score for this scale ranges from 0 to 52, with higher scores indicative of greater catastrophic thinking. The Persian version of the Pain Catastrophizing Scale is a reliable and valid instrument in measuring pain catastrophizing.36,37 Tampa Scale of kinesiophobia (TSK) The Iranian version of the TSK will be used to evaluate kinesiophobia. This scale consists of 17 indices, each as a Likert 4 points measure ranging from totally disagrees to totally agree, which has been previously confirmed regarding validity and reliability.38 Pain Vigilance and Awareness Questionnaire (PVAQ) The Persian version of the PVAQ will be used to assess patients' attention to pain. It is a 16-item criterion of pain attention that assesses awareness, alertness, vigilance, and pain observation. Scores range from 0 to 80, and high scores are related to over-care for pain.39 The validity and reliability of Persian PVAQ has been evaluated by Nasrollahi et al. (2014).40 Brief Illness Perception Questionnaire (BIPQ) The Brief IPQ is a nine-item scale designed to rapidly assess cognitive and emotional representations of the disease. The range of scores of the first 8 questions is from 1 to 10. A higher score indicates a more threatening view of the disease, i.e., the person has a wrong perception of the disease. Question 9 The answer is open and examines the three main causes of the disease in order. Evidence shows the Brief IPQ to be a valid and reliable measure of illness perceptions in a variety of illness groups.41,42 The Persian version of the BIPQ will be used to evaluate the five cognitive illness representations on a five-point Likert scale.43 Short Form Health Survey (SF36) SF36 is a general health assessment tool that includes eight subscales: physical function, physical limitation, physical pain, general health, vitality, social functioning, mental health problems and mental health, which together constitute two measures: physical health summary and mental health summary. In addition, a question that examines changes in a person's health over a period of one year. These eight subscales are scored from 0 to 100, with higher scores indicating better health. The validated Iranian version of the SF-36 will be used to measure the health-related quality of life among the general population.44,45 Global perceived effect (GPE) GPE rated on a 7-point scale (1 = completely recovered, 7 = worse than ever) to assess recovery. These ratings will be dichotomized into “improved” (“completely recovered” and “much improved”) versus “not improved” (“slightly improved,” “not changed,” “slightly worsened,” “much worsened,” “worse than ever”). Statistics The statistical analysis of the primary outcome measures will be performed according to an intention- to-treat analysis to handle non-adherence subjects. We will proceed with a repeated measures mixed model with patients as random effect and time (baseline, 1-2 days after treatment, and three months later) and treatment arm (PNE plus routine physical therapy or routine physical therapy alone) as fixed effects, and with adjustments for baseline imbalance. No imputation will take place. Secondary outcomes and other endpoints will be analyzed similarly to the primary outcome. The frequency of adverse events will be compared between groups at the 3-month follow-up using a Poisson regression model with robust error variance. Categorical outcomes will be analyzed using a Χ2 test, Fisher exact test, or a Mann-Whitney U test as appropriate. A per-protocol analysis will be performed for the primary outcome, excluding patients who had poor adherence to the intervention, defined as participating in less than 75% of the exercise sessions and not attending both PNE sessions. A 95% confidence interval (CI) will be interpreted as a lack of a clinically meaningful difference between groups. P values and 95% CIs will be presented. All authors will have access to the final anonymized trial dataset. Trial Steering Committee The title page presents the members of the trial steering committee. All members participated in the conception of the study design and procured funding. The principal investigator (Kouhzad H) is coordinating the ongoing trial. The trial steering committee reviews the progress of the trial and agrees to the necessary changes in the protocol if any. Knowledge translation What is "already known" in this topic: Limited studies have examined the effect of pain neuroscience education on the treatment of people with chronic neck pain. Pain education vs. routine physical therapy in chronic neck pain Eur J Transl Myol 32 (3): 10674, 2022 doi: 10.4081/ejtm.2022.10674 - 6 - What this article adds In this study, the effect of pain neuroscience education will be investigated only on people with chronic neck pain with central sensitization involvement. Data Collection and Management All obtained results will be collected using a test score protocol or fulfilling questionnaires and, after that, entered into Excel (version 2016, Microsoft Corporation, Redmond, WA, USA). From Excel, data will be transferred into SPSS version 25.0 (SPSS Inc., Chicago, IL, USA) for statistical analyses. All collected test score protocols and questionnaires will be kept in a locked place as backup. Access to study data is restricted only for investigators and anyone cannot be accessed without permission. Publication Results will be published regardless of the outcome. Authorship will be determined based on the guidelines from the International Committee of Medical Journal Editors. The authors do not have any publication restrictions. Discussion This trial aims to investigate the effects of PNE combined with routine physical therapy compared to routine physical therapy alone in regard to psychological factors, physical performance, and the level of pain in patients with CNP. To the best of our knowledge, this is the first clinical trial conducted to evaluate the potential impact of PNE in this group of patients. This study will desire to determine whether the combination of PNE could regulate outcomes of patients with CNP. This trial will be conducted using randomized allocation, double-blinded method, and clinically applicable interventions. The study interventions are conducted in clinical settings, thereby enhancing the possibility of future implementation of the treatments in the health care systems. These would be strengths of this trial. On the limitation's aspects, it is noteworthy that the outcomes will be measured post intervention and 3 months after the interventions. Since the CNP is a chronic condition, longer follow-up periods would be beneficial to detect the impacts of interventions that could appear subsequently and also allows to compare the outcomes in various periods. Because patients in this study have chronic pain, the use of analgesics is unavoidable. In order to eliminate the effect of this possible confounder, it is better to pay attention to such cases in future studies. List of acronyms BIPQ - Brief Illness Perception Questionnaire CERT - Consensus on Exercise Reporting Template CNP - chronic neck pain GPE - Global perceived effect NDI - neck disability index PCS - Pain catastrophizing scale PNE - pain neuroscience education PVAQ - Pain Vigilance and Awareness Questionnaire SF36 - Short Form Health Survey SPIRIT - Standard Protocol Items: Recommendations for Interventional Trials TIDieR - Template for Intervention Description and Replication TSK - Tampa Scale of kinesiophobia Contributions of Authors FS, HKM, MS, FD and GN participated in conception and design of the study, acquisition, analysis and interpretation of data, wrote the manuscript, performed literature review, article drafting and revision, reviewed and edited the manuscript critically, all authors have readed and approved the final editedversion. Acknowledgments This study is part of PhD thesis of Farzaneh Soleimani. This study will be supported by Ahvaz Jundishapur University of Medical Sciences (Grant number: PHT- 0010). Funding This work was supported by the Ahvaz Jundishapur University of Medical Sciences. Conflict of Interest The authors declare no conflict of interests. Ethical Publication Statement We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Corresponding Author Hosein Kouhzad Mohamadi, Musculoskeletal Rehabilitation Research Center Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran ORCID iD: 0000-0003-1567-9151 E-mail: kouhzad@yahoo.com E-mails and ORCID iD of co-authors Farzaneh Soleiman: Soleimani_pt.1391@yahoo.com ORCID iD: 0000-0002-1399-3983 Maryam Saadat: maryamsaadat2008@yahoo.com ORCID iD: 0000-0002-8337-0976 Fateme Derisfard: f_derisfard@yahoo.com ORCID iD: 0000-0002-4272-5136 Gholamhossein Nassadj: nassadj@yahoo.com ORCID iD: 0000-0002-7968-1093 References 1. Picavet HS, Schouten JS. Musculoskeletal pain in the Netherlands: prevalences, consequences and risk groups, the DMC (3)-study. Pain. 2003 mailto:kouhzad@yahoo.com mailto:Soleimani_pt.1391@yahoo.com mailto:maryamsaadat2008@yahoo.com mailto:f_derisfard@yahoo.com mailto:nassadj@yahoo.com Pain education vs. routine physical therapy in chronic neck pain Eur J Transl Myol 32 (3): 10674, 2022 doi: 10.4081/ejtm.2022.10674 - 7 - Mar;102(1-2):167-78. doi: 10.1016/s0304- 3959(02)00372-x. 2. Bier JD, Scholten-Peeters WGM, Staal JB, Pool J, van Tulder MW, Beekman E, Knoop J, Meerhoff G, Verhagen AP. Clinical Practice Guideline for Physical Therapy Assessment and Treatment in Patients With Nonspecific Neck Pain. Phys Ther. 2018 1;98(3):162-171. doi: 10.1093/ptj/pzx118. 3. van Wilgen CP, Keizer D. The sensitization model to explain how chronic pain exists without tissue damage. Pain Manag Nurs. 2012 Mar;13(1):60-5. doi: 10.1016/j.pmn.2010.03.001. Epub 2010 Jul 22. 4. Nijs J, Van Houdenhove B, Oostendorp RA. Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice. Man Ther. 2010 Apr;15(2):135-41. doi: 10.1016/j.math.2009.12.001. Epub 2009 Dec 24. 5. Nijs J, Paul van Wilgen C, Van Oosterwijck J, van Ittersum M, Meeus M. How to explain central sensitization to patients with 'unexplained' chronic musculoskeletal pain: practice guidelines. Man Ther. 2011 Oct;16(5):413-8. doi: 10.1016/j.math.2011.04.005. Epub 2011 May 31. 6. Nijs J, Meeus M, Cagnie B, Roussel NA, Dolphens M, Van Oosterwijck J, Danneels L. A modern neuroscience approach to chronic spinal pain: combining pain neuroscience education with cognition-targeted motor control training. Phys Ther. 2014 May;94(5):730-8. doi: 10.2522/ptj.20130258. Epub 2014 Jan 30. 7. Roldán-Jiménez C, Pérez-Cruzado D, Neblett R, Gatchel R, Cuesta-Vargas A. Central Sensitization in Chronic Musculoskeletal Pain Disorders in Different Populations: A Cross-Sectional Study. Pain Med. 2020 Nov 1;21(11):2958-2963. doi: 10.1093/pm/pnaa069. Erratum in: Pain Med. 2021 Mar 18;22(3):770. 8. Van Oosterwijck J, Nijs J, Meeus M, Truijen S, Craps J, Van den Keybus N, Paul L. Pain neurophysiology education improves cognitions, pain thresholds, and movement performance in people with chronic whiplash: a pilot study. J Rehabil Res Dev. 2011;48(1):43-58. doi: 10.1682/jrrd.2009.12.0206. 9. Meeus M, Nijs J, Van Alsenoy V, Van Oosterwijck J, Truijen S, Pain neurophysiology education improves pain beliefs in patients with chronic fatigue syndrome: A clinical experiment. In Oral presentation at the 6th Congress “Pain in Europe” of the European Federation of International Association for the Study of Pain (IASP) Chapters (EFIC), 8-12 September 2009, Lisbon, Portugal (Oral presentation at the 6th Congress “Pain in Europe” of the European Federation of International Association for the Study of Pain (IASP) Chapters (EFIC), 8-12 September 2009, Lisbon, Portugal). 10. 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 Aug;91(8):1153-9. doi: 10.1016/j.apmr.2010.04. 020 11. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, Hróbjartsson A, Mann H, Dickersin K, Berlin JA, Doré CJ, Parulekar WR, Summerskill WS, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013 Feb 5;158(3):200-7. doi: 10.7326/0003-4819-158-3- 201302050-00583. 12. Hoffmann TC, Glasziou PP, Boutron I, Milne R, Perera R, Moher D, Altman DG, Barbour V, Macdonald H, Johnston M, Lamb SE, Dixon- Woods M, McCulloch P, Wyatt JC, Chan AW, Michie S. Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide. BMJ. 2014 Mar 7;348: g1687. doi: 10.1136/bmj.g1687. 13. Slade SC, Dionne CE, Underwood M, Buchbinder R. Consensus on Exercise Reporting Template (CERT): Explanation and Elaboration Statement. Br J Sports Med. 2016 Dec;50(23):1428-1437. doi: 10.1136/bjsports-2016-096651. Epub 2016 Oct 5. 14. Beltran-Alacreu H, López-de-Uralde-Villanueva I, Fernández-Carnero J, La Touche R. Manual Therapy, Therapeutic Patient Education, and Therapeutic Exercise, an Effective Multimodal Treatment of Nonspecific Chronic Neck Pain: A Randomized Controlled Trial. Am J Phys Med Rehabil. 2015 Oct;94(10 Suppl 1):887-97. doi: 10.1097/PHM.0000000000000293. 15. Tsakitzidis G, Remmen R, Dankaerts W, Van Royen P. Non-specific neck pain and evidence- based practice. European Scientific Journal. ESJ, 2013; 9(3). doi: 10.19044/esj.2013.v9n3p%p. 16. Malfliet A, Kregel J, Coppieters I, De Pauw R, Meeus M, Roussel N, Cagnie B, Danneels L, Nijs J. Effect of Pain Neuroscience Education Combined With Cognition-Targeted Motor Control Training on Chronic Spinal Pain: A Randomized Clinical Trial. JAMA Neurol. 2018 Jul 1;75(7):808-817. doi: 10.1001/jamaneurol. 2018.0492. Erratum in: JAMA Neurol. 2019 Mar 1;76(3):373. 17. Matias BA, Vieira I, Pereira A, Duarte M, Silva AG. Pain neuroscience education plus exercise compared with exercise in university students with chronic idiopathic neck pain. Int J Therapy And Rehabilitation. 2019;26(7):1-14. https://www. Pain education vs. routine physical therapy in chronic neck pain Eur J Transl Myol 32 (3): 10674, 2022 doi: 10.4081/ejtm.2022.10674 - 8 - magonlinelibrary.com/doi/abs/10.12968/ijtr.2018.0 084 18. Chapman CR, Casey KL, Dubner R, Foley KM, Gracely RH, Reading AE. Pain measurement: an overview. Pain. 1985 May;22(1):1-31. doi: 10.1016/0304-3959(85)90145-9. 19. Dworkin RH, Turk DC, Revicki DA, Harding G, Coyne KS, Peirce-Sandner S, Bhagwat D, Everton D, Burke LB, Cowan P, Farrar JT, Hertz S, Max MB, Rappaport BA, Melzack R. Development and initial validation of an expanded and revised version of the Short-form McGill Pain Questionnaire (SF-MPQ-2). Pain. 2009 Jul;144(1- 2):35-42. doi: 10.1016/j.pain.2009.02.007. Epub 2009 Apr 7. 20. Lovejoy TI, Turk DC, Morasco BJ. Evaluation of the psychometric properties of the revised short- form McGill Pain Questionnaire. J Pain. 2012 Dec;13(12):1250-7. doi: 10.1016/j.jpain.2012.09. 011. 21. Bartholomew C, Edwards L, Lack S. Pressure pain thresholds in adults with patellofemoral pain and patellofemoral joint osteoarthritis: a case-control study. Scand J Pain. 2019 Jun 12;19(4):713-723. doi: 10.1515/sjpain-2019-0026. 22. Whiteside A, Hansen S, Chaudhuri A. Exercise lowers pain threshold in chronic fatigue syndrome. Pain. 2004 Jun;109(3):497-499. doi: 10.1016/ j. pain.2004.02.029. 23. Ferreira J, Matias B, Silva AG. Pressure pain thresholds in university students with undertreated neck pain: comparison with asymptomatic individuals, reliability and measurement error. European J Physiotherapy. 2020;22(5):284-9. https://doi.org/10.1080/21679169.2019.1614666. 24. Dolphens M, Nijs J, Cagnie B, Meeus M, Roussel N, Kregel J, Malfliet A, Vanderstraeten G, Danneels L. Efficacy of a modern neuroscience approach versus usual care evidence-based physiotherapy on pain, disability and brain characteristics in chronic spinal pain patients: protocol of a randomized clinical trial. BMC Musculoskelet Disord. 2014 May 8;15:149. doi: 10.1186/1471-2474-15-149. 25. Kinser AM, Sands WA, Stone MH. Reliability and validity of a pressure algometer. J Strength Cond Res. 2009 Jan;23(1):312-4. doi: 10.1519/jsc.0b013e31818f051c. 26. Bisset LM, Evans K, Tuttle N. Reliability of 2 protocols for assessing pressure pain threshold in healthy young adults. J Manipulative Physiol Ther. 2015 May;38(4):282-7. doi: 10.1016/j.jmpt.2015. 03.001. Epub 2015 Apr 27. 27. Noorollahzadeh K, Kahrizi S, Fesharaki MG, Heidarian M, Neblett R, Behzadipour S. Cross- cultural adaptation and psychometric validation of the Persian version of the central sensitization inventory. Musculoskelet Sci Pract. 2021 Feb; 51:102314. doi: 10.1016/j.msksp.2020. 102314. Epub 2020 Dec 10. 28. Cuesta-Vargas AI, Neblett R, Chiarotto A, Kregel J, Nijs J, van Wilgen CP, Pitance L, Knezevic A, Gatchel RJ, Mayer TG, Viti C, Roldan-Jiménez C, Testa M, Caumo W, Jeremic-Knezevic M, Luciano JV. Dimensionality and Reliability of the Central Sensitization Inventory in a Pooled Multicountry Sample. J Pain. 2018 Mar;19(3):317-329. doi: 10.1016/j.jpain.2017.11.006. Epub 2017 Dec 2. 29. Neblett R, Hartzell MM, Williams M, Bevers KR, Mayer TG, Gatchel RJ. Use of the Central Sensitization Inventory (CSI) as a treatment outcome measure for patients with chronic spinal pain disorder in a functional restoration program. Spine J. 2017 Dec;17(12):1819-1829. doi: 10.1016/j.spinee.2017.06.008. Epub 2017 Jun 12. 30. Scerbo T, Colasurdo J, Dunn S, Unger J, Nijs J, Cook C. Measurement Properties of the Central Sensitization Inventory: A Systematic Review. Pain Pract. 2018 Apr;18(4):544-554. doi: 10.1111/papr.12636. Epub 2017 Nov 20. 31. Moseley GL, Nicholas MK, Hodges PW. A randomized controlled trial of intensive neurophysiology education in chronic low back pain. Clin J Pain. 2004 Sep-Oct;20(5):324-30. doi: 10.1097/00002508-200409000-00007. 32. Moseley L. Unraveling the barriers to reconceptualization of the problem in chronic pain: the actual and perceived ability of patients and health professionals to understand the neurophysiology. J Pain. 2003 May;4(4):184-9. doi: 10.1016/s1526-5900(03)00488-7. 33. Catley MJ, O'Connell NE, Moseley GL. How good is the neurophysiology of pain questionnaire? A Rasch analysis of psychometric properties. J Pain. 2013 Aug;14(8):818-27. doi: 10.1016 /j.jpain.2013.02.008. Epub 2013 May 4. 34. Mousavi SJ, Parnianpour M, Montazeri A, Mehdian H, Karimi A, Abedi M, Ashtiani AA, Mobini B, Hadian MR. Translation and validation study of the Iranian versions of the Neck Disability Index and the Neck Pain and Disability Scale. Spine (Phila Pa 1976). 2007 Dec 15;32(26): E825- 31. doi: 10.1097/BRS.0b013e31815ce6dd. 35. Salehi R, Negahban H, Saghayezhian N, Saadat M. The Responsiveness of the Persian Version of Neck Disability Index and Functional Rating Index Following Physiotherapy Intervention in People with Chronic Neck Pain. Iran J Med Sci. 2019 Sep;44(5):390-396. doi: 10.30476/ijms.2019. 44963. 36. Raeissadat SA, Sadeghi S, Montazeri A. Validation of the pain catastrophizing scale (PCS) in Iran. J Basic Appl Sci Res. 2013;3(9):376-80. www.textroad.com 37. Rahmati N, Asghari Moghadam M A, SHAIRI M, Paknejad M, Rahmati Z, Ghassami M, Marofi N, Pain education vs. routine physical therapy in chronic neck pain Eur J Transl Myol 32 (3): 10674, 2022 doi: 10.4081/ejtm.2022.10674 - 9 - Naeb Aghaei H. A Study of the Psychometric Properties of the Pain Catastrophizing Scale Amongst Iranian Patients with Chronic Persistent Pain. sjimu. 2017; 25 (1) :63-79. URL: http://sjimu.medilam.ac.ir/article-1-2114-en.html 38. Askary-Ashtiani A, Ebrahimi-Takamejani I, Torkaman G, Amiri M, Mousavi SJ. Reliability and validity of the Persian versions of the fear avoidance beliefs questionnaire and Tampa Scale of Kinesiophobia in patients with neck pain. Spine (Phila Pa 1976). 2014 Aug 15;39(18): E1095-102. doi: 10.1097/BRS.0000000000000438. 39. Roelofs J, Peters ML, McCracken L, Vlaeyen JWS. The pain vigilance and awareness questionnaire (PVAQ): further psychometric evaluation in fibromyalgia and other chronic pain syndromes. Pain. 2003 Feb;101(3):299-306. doi: 10.1016/S0304-3959(02)00338-X. 40. Nasrollahi B, Dehghani M, Ghasedi M. A study on the role of selective attention, vigilance and ambivalence over emotional expressiveness for predicting pain severity in patients with chronic musculoskeletal pains. Hormozgan Med J. 2014;18(5):346-56. https://www.sid.ir/en/Journal/ ViewPaper.aspx?ID=531618. 41. Broadbent E, Petrie KJ, Main J, Weinman J. The brief illness perception questionnaire. J Psychosom Res. 2006 Jun;60(6):631-7. doi: 10.1016/j.jpsy chores.2005.10.020. 42. Broadbent E, Wilkes C, Koschwanez H, Weinman J, Norton S, Petrie KJ. A systematic review and meta-analysis of the Brief Illness Perception Questionnaire. Psychol Health. 2015;30(11):1361- 85. doi: 10.1080/08870446.2015.1070851. Epub 2015 Aug 26. 43. Seydi M, Akhbari B, Ghasem Abad SK, Jaberzadeh S, Saeedi A, Ashrafi A, Shakoorianfard MA. Psychometric properties of the Persian version of the brief illness questionnaire in Iranian with non-specific chronic neck pain. J Bodyw Mov Ther. 2021 Oct;28:323-331. doi: 10.1016/j.jbmt.2021.06.002. Epub 2021 Jun 12. 44. Montazeri A, Goshtasebi A, Vahdaninia M, Gandek B. The Short Form Health Survey (SF- 36): translation and validation study of the Iranian version. Qual Life Res. 2005 Apr;14(3):875-82. doi: 10.1007/s11136-004-1014-5. 45. Eshaghi S-R, Ramezani MA, Shahsanaee A, Pooya A. Validity and reliability of the Short Form-36 Items questionnaire as a measure of quality of life in elderly Iranian population. Am J Appl Sci. 2006;3(3):1763-6. https://www.sid.ir/en/journal/ ViewPaper.aspx?ID=22574. Disclaimer All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Submission: June 13, 2022 Revision received: June 22, 2022 Accepted for publication: June 33, 2022