Pain neuroscience education and physical exercise for patients with chronic spinal pain in primary healthcare: a randomised trial protocol

Miguel A Galán-Martín, Federico Montero-Cuadrado, Enrique Lluch-Girbes, M Carmen Coca-López, Agustín Mayo-Iscar, Antonio Cuesta-Vargas, Miguel A Galán-Martín, Federico Montero-Cuadrado, Enrique Lluch-Girbes, M Carmen Coca-López, Agustín Mayo-Iscar, Antonio Cuesta-Vargas

Abstract

Background: Chronic musculoskeletal pain affects more than 20% of the population, and the prevalence is increasing, causing suffering, loss of quality of life, disability, and an enormous expenditure on healthcare resources. The most common location for chronic pain is the spine. Many of the treatments used are mainly passive (pharmacological and invasive) and poor outcomes. The treatments currently applied in the public health system do not comply with the recommendations of the main clinical practice guidelines, which suggest the use of educational measures and physical exercise as the first-line treatment. A protocol based on active coping strategies is described, which will be evaluated through a clinical trial and which could facilitate the transfer of the recommendations of the clinical practice guidelines to a primary care setting.

Methods: Randomised and multicentre clinical trials, which will be carried out in 10 Primary Care centres. The trial will compare the effect of a Pain Neuroscience Education program (six sessions, 10 h) and group physical exercise (18 sessions program carried out in six weeks, 18 h), with usual care physiotherapy treatment. Group physical exercise incorporates dual tasks, gaming, and reinforcement of contents of the educational program. The aim is to assess the effect of the intervention on quality of life, as well as on pain, disability, catastrophism, kinesiophobia, central sensitisation, and drug use. The outcome variables will be measured at the beginning of the intervention, after the intervention (week 11), at six months, and a year.

Discussion: Therapeutic interventions based on active coping strategies are essential for the treatment of chronic pain and the sustainability of the Public Health System. Demonstrating whether group interventions have an effect size is essential for optimising resources in such a prevalent problem.

Trial registration: NCT03654235 "Retrospectively registered" 31 August 2018.

Keywords: Chronic pain; Chronic spinal pain; Pain neuroscience education; Physical exercise; Primary care; Treatment protocol.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Temporal distribution of program sessions (experimental group)
Fig. 2
Fig. 2
Structure of sessions (experimental group)
Fig. 3
Fig. 3
Flowchart of the study

References

    1. Langley PC. The prevalence, correlates and treatment of pain in the European Union. Curr Med Res Opin [Internet]. 2011 Feb 11 [cited 2016 Mar 25];27(2):463–480. Available from:
    1. Breivik H, Eisenberg E, O’Brien T. The individual and societal burden of chronic pain in Europe: the case for strategic prioritisation and action to improve knowledge and availability of appropriate care. BMC Public Health [Internet]. 2013;13(1):1229. Available from:
    1. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England) [Internet]. 2018 Nov 10 [cited 2019 Apr 12];392(10159):1789–1858. Available from:
    1. Langley Paul, Müller-Schwefe Gerhard, Nicolaou Andrew, Liedgens Hiltrud, Pergolizzi Joseph, Varrassi Giustino. The societal impact of pain in the European Union: health-related quality of life and healthcare resource utilization. Journal of Medical Economics. 2010;13(3):571–581. doi: 10.3111/13696998.2010.516709.
    1. Gaskin Darrell J., Richard Patrick. The Economic Costs of Pain in the United States. The Journal of Pain. 2012;13(8):715–724. doi: 10.1016/j.jpain.2012.03.009.
    1. Jordan KP, Kadam UT, Hayward R, Porcheret M, Young C, Croft P. Annual consultation prevalence of regional musculoskeletal problems in primary care: an observational study. BMC Musculoskelet Disord [Internet]. 2010 Dec 2 [cited 2019 Apr 8];11(1):144. Available from:
    1. Hurwitz EL, Randhawa K, Yu H, Côté P, Haldeman S. The Global Spine Care Initiative: a summary of the global burden of low back and neck pain studies. Eur Spine J [Internet]. 2018; Available from: .
    1. Nijs J, Meeus M, Oosterwijck J Van, Roussel N, Kooning M De, Ickmans K, et al. Treatment of central sensitization in patients with ‘ unexplained ’ chronic pain : what options do we have? Expert Opin Pharmacother [Internet]. 2011 May 22 [cited 2019 May 28];12(7):1–12. Available from:
    1. Jonas WB, Crawford C, Colloca L, Kriston L, Linde K, Moseley B, et al. Are invasive procedures effective for chronic pain? A systematic review. Pain Med [Internet]. 2018 Sep 10 [cited 2018 Dec 14]; Available from:
    1. Woolf Clifford J. Central sensitization: Implications for the diagnosis and treatment of pain. Pain. 2011;152(Supplement):S2–S15. doi: 10.1016/j.pain.2010.09.030.
    1. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10(9):895–926. doi: 10.1016/j.jpain.2009.06.012.
    1. Woolf CJ, Bennett GJ, Doherty M, Dubner R, Kidd B, Koltzenburg M, et al. Towards a mechanism-based classification of pain? Pain. 1998;77(3):227–229. doi: 10.1016/S0304-3959(98)00099-2.
    1. Nijs J, Van Houdenhove B, Oostendorp RAB. Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice. Man Ther [Internet]. 2010 Apr [cited 2016 Mar 24];15(2):135–141. Available from:
    1. Apkarian A V. Chronic back pain is associated with decreased prefrontal and thalamic gray matter Ddensity. J Neurosci [Internet]. 2004 Nov 17 [cited 2016 Mar 24];24(46):10410–10415. Available from:
    1. Wood PB. Variations in brain gray matter associated with chronic pain. Curr Rheumatol Rep [Internet]. 2010 Dec 21 [cited 2016 Mar 24];12(6):462–469. Available from:
    1. May A. Chronic pain may change the structure of the brain. Pain. 2008;137(1):7–15. doi: 10.1016/j.pain.2008.02.034.
    1. Smallwood Rachel F., Laird Angela R., Ramage Amy E., Parkinson Amy L., Lewis Jeffrey, Clauw Daniel J., Williams David A., Schmidt-Wilcke Tobias, Farrell Michael J., Eickhoff Simon B., Robin Donald A. Structural Brain Anomalies and Chronic Pain: A Quantitative Meta-Analysis of Gray Matter Volume. The Journal of Pain. 2013;14(7):663–675. doi: 10.1016/j.jpain.2013.03.001.
    1. Rodriguez-Raecke R, Niemeier A, Ihle K, Ruether W, May A. Brain gray matter decrease in chronic pain ss the consequence and not the cause of pain. J Neurosci [Internet]. 2009 Nov 4 [cited 2016 Mar 24];29(44):13746–13750. Available from:
    1. Daenen Liesbeth, Nijs Jo, Roussel Nathalie, Wouters Kristien, Van Loo Michel, Cras Patrick. Dysfunctional pain inhibition in patients with chronic whiplash-associated disorders: an experimental study. Clinical Rheumatology. 2012;32(1):23–31. doi: 10.1007/s10067-012-2085-2.
    1. Hodges Paul W., Tucker Kylie. Moving differently in pain: A new theory to explain the adaptation to pain. Pain. 2011;152(Supplement):S90–S98. doi: 10.1016/j.pain.2010.10.020.
    1. Tsao H., Galea M. P., Hodges P. W. Reorganization of the motor cortex is associated with postural control deficits in recurrent low back pain. Brain. 2008;131(8):2161–2171. doi: 10.1093/brain/awn154.
    1. Salter MW. The neurobiology of central sensitization. J Musculoskelet Pain. 2002;10(1–2):23–33. doi: 10.1300/J094v10n01_03.
    1. Fletcher Claire, Bradnam Lynley, Barr Christopher. The relationship between knowledge of pain neurophysiology and fear avoidance in people with chronic pain: A point in time, observational study. Physiotherapy Theory and Practice. 2016;32(4):271–276. doi: 10.3109/09593985.2015.1138010.
    1. Leeuw Maaike, Goossens Mariëlle E. J. B., Linton Steven J., Crombez Geert, Boersma Katja, Vlaeyen Johan W. S. The Fear-Avoidance Model of Musculoskeletal Pain: Current State of Scientific Evidence. Journal of Behavioral Medicine. 2006;30(1):77–94. doi: 10.1007/s10865-006-9085-0.
    1. Cieza Alarcos, Stucki Gerold, Weigl Martin, Kullmann Lajos, Stoll Thomas, Kamen Leonard, Kostanjsek Nenad, Walsh Nicolas. ICF Core Sets for chronic widespread pain. Journal of Rehabilitation Medicine. 2004;36(0):63–68. doi: 10.1080/16501960410016046.
    1. Nijs J., Meeus M., Cagnie B., Roussel N. A., 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. Physical Therapy. 2014;94(5):730–738. doi: 10.2522/ptj.20130258.
    1. Foster NE, Anema JR, Cherkin D, Chou R, Cohen SP, Gross DP, et al. Prevention and treatment of low back pain: evidence, challenges, and promising directions. Lancet [Internet]. 2018 Jun [cited 2018 Mar 26];391(10137):2368–83. Available from: .
    1. Wong J.J., Côté P., Sutton D.A., Randhawa K., Yu H., Varatharajan S., Goldgrub R., Nordin M., Gross D.P., Shearer H.M., Carroll L.J., Stern P.J., Ameis A., Southerst D., Mior S., Stupar M., Varatharajan T., Taylor-Vaisey A. Clinical practice guidelines for the noninvasive management of low back pain: A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. European Journal of Pain. 2016;21(2):201–216. doi: 10.1002/ejp.931.
    1. Stochkendahl MJ, Kjaer P, Hartvigsen J, Kongsted A, Aaboe J, Andersen MØMM, et al. National Clinical Guidelines for non-surgical treatment of patients with recent onset low back pain or lumbar radiculopathy. Eur Spine J [Internet] 2018;27(1):60–75. doi: 10.1007/s00586-017-5099-2.
    1. Qaseem Amir, Wilt Timothy J., McLean Robert M., Forciea Mary Ann. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Annals of Internal Medicine. 2017;166(7):514. doi: 10.7326/M16-2367.
    1. Babatunde Opeyemi O., Jordan Joanne L., Van der Windt Danielle A., Hill Jonathan C., Foster Nadine E., Protheroe Joanne. Effective treatment options for musculoskeletal pain in primary care: A systematic overview of current evidence. PLOS ONE. 2017;12(6):e0178621. doi: 10.1371/journal.pone.0178621.
    1. Louw Adriaan, Diener Ina, Butler David S., Puentedura Emilio J. The Effect of Neuroscience Education on Pain, Disability, Anxiety, and Stress in Chronic Musculoskeletal Pain. Archives of Physical Medicine and Rehabilitation. 2011;92(12):2041–2056. doi: 10.1016/j.apmr.2011.07.198.
    1. Geneen LJ, Martin DJ, Adams N, Clarke C, Dunbar M, Jones D, et al. Effects of education to facilitate knowledge about chronic pain for adults: a systematic review with meta-analysis. Syst Rev [Internet]. 2015;4(1):132. Available from:
    1. Daenen Liesbeth, Varkey Emma, Kellmann Michael, Nijs Jo. Exercise, Not to Exercise, or How to Exercise in Patients With Chronic Pain? Applying Science to Practice. The Clinical Journal of Pain. 2015;31(2):108–114. doi: 10.1097/AJP.0000000000000099.
    1. Geneen L, Smith B, Clarke C, Martin D, Colvin LA, Moore RA. Physical activity and exercise for chronic pain in adults: an overview of Cochrane reviews. Cochrane Database Syst Rev [Internet]. 2017;(2017 Issue 1):4. Available from:
    1. Snodgrass Suzanne J., Heneghan Nicola R., Tsao Henry, Stanwell Peter T., Rivett Darren A., Van Vliet Paulette M. Recognising neuroplasticity in musculoskeletal rehabilitation: A basis for greater collaboration between musculoskeletal and neurological physiotherapists. Manual Therapy. 2014;19(6):614–617. doi: 10.1016/j.math.2014.01.006.
    1. Juul Tina, Søgaard Karen, Davis Aileen M., Roos Ewa M. Psychometric properties of the Neck OutcOme Score, Neck Disability Index, and Short Form–36 were evaluated in patients with neck pain. Journal of Clinical Epidemiology. 2016;79:31–40. doi: 10.1016/j.jclinepi.2016.03.015.
    1. Rogge Ann-Kathrin, Röder Brigitte, Zech Astrid, Hötting Kirsten. Exercise-induced neuroplasticity: Balance training increases cortical thickness in visual and vestibular cortical regions. NeuroImage. 2018;179:471–479. doi: 10.1016/j.neuroimage.2018.06.065.
    1. Amir S, Batouli H, Saba V, Amir S. At least eighty percent of brain grey matter is modifiable by physical activity: a review study medical imaging view project electromagnetic waves view project at least eighty percent of brain grey matter is modifiable by physical activity: a review study. Behav Brain Res. 2017;332:204–217. doi: 10.1016/j.bbr.2017.06.002.
    1. Ray Chester A., Carter Jason R. Central modulation of exercise-induced muscle pain in humans. The Journal of Physiology. 2007;585(1):287–294. doi: 10.1113/jphysiol.2007.140509.
    1. Louw A, Zimney K, Puentedura EJ, Diener I. The efficacy of pain neuroscience education on musculoskeletal pain: a systematic review of the literature. Physiother theory Pract [Internet]. 2016;3985(September):1–24. Available from: .
    1. Malfliet A, Kregel J, Coppieters I, Pauw R De, Meeus M, Roussel N, et al. Effect of pain neuroscience education combined with cognition-targeted Motor Control Training on Chronic Spinal Pain: A Randomized Clinical Trial. JAMA Neurol [Internet]. 2018; Available from:
    1. Marques ES, Meziat Filho NA de M, Ferreira P dos S, Andrade FG de, Ramsay EM, Amaral Corrêa L, et al. Group pain neuroscience education combined with supervised exercises reduces pain and improves function of Brazilian women with central sensitisation and a low level of education: a single-subject study. Eur J Physiother [Internet]. 2019;21(4):224–32. Available from: .
    1. Edwards Robert R., Dworkin Robert H., Sullivan Mark D., Turk Dennis C., Wasan Ajay D. The Role of Psychosocial Processes in the Development and Maintenance of Chronic Pain. The Journal of Pain. 2016;17(9):T70–T92. doi: 10.1016/j.jpain.2016.01.001.
    1. Burke SM, Carron A V, Eys MA, Ntoumanis N, Estabrooks PA. Group versus individual approach? A meta-analysis of the effectiveness of interventions to promote physical activity. Sport Exerc Psychol Rev [Internet]. 2006 [cited 2018 Dec 17];2:1–13. Available from:
    1. Yorks DM, Frothingham CA, Schuenke MD. Effects of group fitness classes on stress and quality of life of medical students. J Am Osteopath Assoc [Internet]. 2017 Nov 1 [cited 2018 Dec 17];117(11):e17. Available from:
    1. Jakobsen Markus D, Sundstrup Emil, Brandt Mikkel, Jay Kenneth, Aagaard Per, Andersen Lars L. Effect of workplace- versus home-based physical exercise on musculoskeletal pain among healthcare workers: a cluster randomized controlled trial. Scandinavian Journal of Work, Environment & Health. 2015;41(2):153–163. doi: 10.5271/sjweh.3479.
    1. Chan An-Wen, Tetzlaff Jennifer M., Altman Douglas G., Laupacis Andreas, Gøtzsche Peter C., Krleža-Jerić Karmela, Hróbjartsson Asbjørn, Mann Howard, Dickersin Kay, Berlin Jesse A., Doré Caroline J., Parulekar Wendy R., Summerskill William S.M., Groves Trish, Schulz Kenneth F., Sox Harold C., Rockhold Frank W., Rennie Drummond, Moher David. SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials. Annals of Internal Medicine. 2013;158(3):200. doi: 10.7326/0003-4819-158-3-201302050-00583.
    1. Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, et al. CONSORT 2010 Explanation and Elaboration: Updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol [Internet]. 2010 Aug 1 [cited 2019 mar 29];63(8):e1–37. Available from: .
    1. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res [Internet]. 1975 Nov 1 [cited 2019 Mar 29];12(3):189–198. Available from:
    1. Llamas Velasco Sara, Llorente Ayuso Lucía, Contador Israel, Bermejo Pareja Félix. Versiones en español del Minimental State Examination (MMSE). Cuestiones para su uso en la práctica clínica. Revista de Neurología. 2015;61(08):363. doi: 10.33588/rn.6108.2015107.
    1. Prochaska JO, DiClemente CC. Transtheoretical therapy: Toward a more integrative model of change. Psychother Theory, Res Pract [Internet]. 1982 [cited 2018 Dec 9];19(3):276–288. Available from:
    1. Prochaska JO. Decision making in the transtheoretical model of behavior change. Med Decis Mak [Internet]. 2008 [cited 2018 Dec 9];28:845–849. Available from:
    1. Nijs J, Kosek E, Oosterwijck J Van, Meeus M, Van Oosterwijck J, Meeus M. Dysfunctional endogenous analgesia during exercise in patients with chronic pain: to exercise or not to exercise? Pain Physician [Internet]. 2012 [cited 2018 Dec 8];15(3 Suppl):205–14. Available from: .
    1. Smith BE, Hendrick P, Bateman M, Holden S, Littlewood C, Smith TO, et al. Musculoskeletal pain and exercise— challenging existing paradigms and introducing new. Br J Sport Med Mon 2018;(0).
    1. Smith Benjamin E, Hendrick Paul, Smith Toby O, Bateman Marcus, Moffatt Fiona, Rathleff Michael S, Selfe James, Logan Pip. Should exercises be painful in the management of chronic musculoskeletal pain? A systematic review and meta-analysis. British Journal of Sports Medicine. 2017;51(23):1679–1687. doi: 10.1136/bjsports-2016-097383.
    1. Thompson Paul D., Arena Ross, Riebe Deborah, Pescatello Linda S. ACSM’s New Preparticipation Health Screening Recommendations from ACSM’s Guidelines for Exercise Testing and Prescription, Ninth Edition. Current Sports Medicine Reports. 2013;12(4):215–217. doi: 10.1249/JSR.0b013e31829a68cf.
    1. Dirección General de Asistencia Sanitaria. Protocolos de Fisioterapia en Atención Primaria [Internet]. Valladolid; 2005. Available from:
    1. SERMEF (Sociedad Española de Medicina Física y Rehabilitación). WEB EJERCICIOS SERMEF – SERMEF [Internet]. [cited 2019 Apr 6]. Available from:
    1. Melzack R. The short-form McGill pain questionnaire. Pain. 1987;30(2):191–197. doi: 10.1016/0304-3959(87)91074-8.
    1. Vilagut G, Valderas JM, Ferrer M, Garin O, López-García E, Alonso J. Interpretación de los cuestionarios de salud SF-36 y SF-12 en España: componentes físico y mental. Med Clin (Barc) [Internet]. 2008 [cited 2018 Jul 6];130(19):726–735. Available from:
    1. Alonso J, Regidor E, Barrio G, Prieto L, Rodríguez C, De la Fuente L. Valores poblacionales de referencia de la versión española del Cuestionario de Salud SF-36. Med Clin (Barc) 1998;111(11):410–416.
    1. Chapman CR, Casey KL, Dubner R, Foley KM, Gracely RH, Reading AE. Pain measurement: an overview. Pain. 1985;22(1):1–31. doi: 10.1016/0304-3959(85)90145-9.
    1. Neziril Alban Y., Scaramozzinol Pasquale, Andersenl Ole K., Dickensonl Anthony H., Arendt-Nielsenl Lars, Curatolol Michele. Reference values of mechanical and thermal pain tests in a pain-free population. European Journal of Pain. 2011;15(4):376–383. doi: 10.1016/j.ejpain.2010.08.011.
    1. Fischer AA. Algometry in diagnosis of musculoskeletal pain and evaluation of treatment outcome: An update. J Musculoskelet Pain [Internet]. 1998 Jan 16 [cited 2017 Feb 3];6(1):5–32. Available from:
    1. Balaguier R, Madeleine P, Vuillerme N. Is one trial sufficient to obtain excellent pressure pain threshold reliability in the low back of asymptomatic individuals? A test-retest study. PLoS One [Internet] 2016;11(8):1–16.
    1. Escobar JCZ, Del Pozo MG, Propin MG. Modificaciones del umbral de dolor en un punto gatillo miofascial tras técnica de energía muscular. Rev la Soc Esp del Dolor. 2010;17(7):313–319. doi: 10.1016/j.resed.2010.09.003.
    1. Park G, Kim CW, Park SB, Kim MJ, Jang SH. Reliability and usefulness of the pressure pain threshold measurement in patients with myofascial pain. Ann Rehabil Med [Internet] 2011;35(3):412–417. doi: 10.5535/arm.2011.35.3.412.
    1. García Campayo J, Rodero B, Alda M, Sobradiel N, Montero J, Moreno S. Validación de la versión española de la escala de la catastrofización ante el dolor (Pain Catastrophizing Scale) en la fibromialgia. Med Clin. 2008;131(13):487–492. doi: 10.1157/13127277.
    1. Sullivan MJL, Bishop SR, Pivik J. The Pain Catastrophizing Scale: Development and validation. Psychol Assess [Internet]. 1995 [cited 2019 Apr 6];7(4):524–532. Available from:
    1. Gómez-Pérez L, López-Martínez AE, Ruiz-Párraga GT. Psychometric properties of the spanish version of the Tampa scale for Kinesiophobia (TSK) J Pain. 2011;12(4):425–435. doi: 10.1016/j.jpain.2010.08.004.
    1. Cuesta-Vargas AI, Roldan-Jimenez C, Neblett R, Gatchel RJ. Cross-cultural adaptation and validity of the Spanish central sensitization inventory. Springerplus [Internet]. 2016 Dec 21 [cited 2016 Oct 22];5(1):1837. Available from:
    1. Scerbo T, Colasurdo J, Dunn S, Unger J, Nijs J, Cook C. Measurement properties of the central sensitization inventory: A systematic review. Pain Pract [Internet]. 2018 Apr 1 [cited 2019 Apr 6];18(4):544–554. Available from:
    1. Kovacs FM, Llobera J, del Real MTG, Abraira V, Gestoso M, Fernández C. Validation of the Spanish version of the Roland–Morris questionnaire. Spine (Phila Pa 1976) 2002;27(5):538–542. doi: 10.1097/00007632-200203010-00016.
    1. Roberts RE, Atrkisson CC, Mendias RM. Assessing the client satisfaction questionnaire in English and Spanish. Hisp J Behav Sci [Internet]. 1984 Dec 25 [cited 2019 Apr 6];6(4):385–396. Available from:
    1. Galán-Martín M, Montero-Cuadrado F. Educación en neurociencia del dolor. Una nueva visión. dossier para pacientes. First edit. Junta de Castilla y León, editor. Junta de Castilla y León: Valladolid; 2018.
    1. Howick Jeremy, Moscrop Andrew, Mebius Alexander, Fanshawe Thomas R, Lewith George, Bishop Felicity L, Mistiaen Patriek, Roberts Nia W, Dieninytė Eglė, Hu Xiao-Yang, Aveyard Paul, Onakpoya Igho J. Effects of empathic and positive communication in healthcare consultations: a systematic review and meta-analysis. Journal of the Royal Society of Medicine. 2018;111(7):240–252. doi: 10.1177/0141076818769477.
    1. Goicoechea A, Echávarri R. Migraña : una pesadilla cerebral [Internet]. Desclée de Brouwer; 2009 [cited 2017 Jul 8]. 342 p. Available from:
    1. Butler D, Moseley L. Explain pain. 2nd ed. Adelaide: NOI group Publications; 2013. p. 133.
    1. Louw A , Puentedura E. Therapeutic neuroscience education : teaching patients about pain : a guide for clinicians. Louisville: International Spine and Pain Institute; 2013. p. 292.
    1. Nijs J, Lluch Girbés E, Lundberg M, Malfliet A, Sterling M. Exercise therapy for chronic musculoskeletal pain: Innovation by altering pain memories. Man Ther [Internet]. 2015 Feb 1 [cited 2017 Nov 27];20(1):216–220. Available from: .
    1. Booth J, Moseley GL, Schiltenwolf M, Cashin A, Davies M, Hübscher M. Exercise for chronic musculoskeletal pain: A biopsychosocial approach. Musculoskeletal Care [Internet]. 2017 Dec 1 [cited 2017 Dec 16];15(4):413–421. Available from:
    1. Cohen S, Janicki-Deverts D, Turner RB, Doyle WJ. Does hugging provide stress-buffering social support? A study of susceptibility to upper respiratory infection and illness. Psychol Sci [Internet]. 2015 Feb [cited 2018 Dec 17];26(2):135–147. Available from: .

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