The Biopsychosocial Model: Understanding the Science of Pain

For hundreds of years, it has been assumed that pain is a direct result of injury. In theory, a greater amount of damage to the tissues of the body should result in a higher degree of pain. This makes intuitive sense, yet has been proven to be overly simplistic.

 

Consider, for example, a study by Liu et al (1). Subjects who were experiencing major pain in one of their knees or shoulders had an MRI taken on both the painful joint as well as the joint on the other side of the body. Amazingly, doctors were unable to tell based off of the images which side was the one in pain. In both the painful side and non-painful side, a similar degree of tissue damage was present.

 

This is not an isolated finding. Many additional studies have found that:

 

  • MRIs of the low back are unable to predict which patients are suffering from pain. Many people with no back pain have major disc herniations or other structural damage (2-9)
  • MRIs of the knee are unable to predict which patients are suffering from knee pain (10-14)
  • MRIs of the shoulder are unable to predict which patients are suffering from shoulder pain (15-18)

 

Clearly, these studies indicate that the connection between injury and pain is more complicated than many may believe.

What is pain?

Pain is a defense mechanism produced by the brain in response to a perceived threat. Many factors are inputted into our brain that influence the perception of pain. Tissue damage is one of these factors, but there are many psychological factors that play a major role as well (19).

 

Amazingly, these psychological factors can sometimes play a larger role than the structural factors in determining pain and treatment outcomes. For example:

 

  • For low back pain, patient’s perceptions of their injury may be a better predictor of treatment outcomes than the severity of the injury (20-24)
  • For ankle injuries, psychosocial factors can predict pain symptoms better than severity of the injury (25-27)
  • For shoulder injury, psychosocial factors predict pain better than severity of injury (28-30)

 

In all of these studies, the psychological factors tended to outweigh the structural factors in determining who would suffer from pain.

 

Nervous System Changes to Chronic Pain

Further evidence of the differentiation between structural damage and pain is evident in the neural changes that occur in patients who suffer from chronic pain.

Patients who are in pain for an extended period of time can often suffer from long-term changes to the way their brain processes pain (31-48).

 

According to Dr. Adriaan Louw in his book Therapeutic Neuroscience Education, “Pain mechanisms due to processing issues, commonly referred to as ‘central sensitization,’ occur due to neuroplastic changes in the dorsal horn of the spinal cord, inappropriate synapsing, neuronal death, sprouting, receptor field expansion, activation of the neuromatrix, changes in neurotransmitters and ion channels in the CNS and brain, and loss of gray matter. In central sensitization, pain is due more to abnormal processing of the nociception by the spinal cord, brainstem and cerebral hemispheres” (49, page 103).

 

These types of patients will require specialized treatment protocols to address the unfavorable effects that have occurred on the nervous system, and may not respond to typical physical therapy approaches that focus exclusively on biomechanical dysfunction.

 

Factors that Affect Pain Perception

Many psychological factors have been shown to affect perceptions of pain. For example:

 

  • Expectations – When subjects expect physical therapy to work, they are more likely to experience greater reductions in pain (50-52). In one interesting study, when subjects in an MRI machine were given a placebo and told that it would relieve their pain, decreased brain activity was seen in the areas of the brain associated with pain perceptions (53)
  • Social support – When subjects receive social support, perceptions of pain are dramatically decreased (54-62). In one study, subjects in an fMRI machine were subjected to electric shocks. When these subjects were allowed to hold their husbands hands, decreased brain activity was seen in the areas of the brain associated with pain (56)
  • Physician empathy – When doctors are communicative with their patients and demonstrate empathy, patients feel less pain compared to less empathetic doctors, even when the treatments are identical (63-67)
  • Therapeutic Neuroscience Education – When physical therapists talk with their patients about the science of pain and explain how sometimes pain can be present even in the absence of any serious pathology, this decreases threat perceptions and can lead to better treatment outcomes (68-80)

 

Taking Pain Science Too Far?

Because pain is created by the brain and can be absent even in the presence of injury or movement dysfunction, I have seen some clinicians claim that injury or movement dysfunction no longer matter. Some have claimed that instead of fixing the way their patients move, they focus on educating them on how there is no “proper way to move” and gradually exposing them to painful movements to help them feel safer and reduce threat perception. I even had one chiropractor tell me that he doesn’t care if all he is doing is creating a placebo effect because pain is all in the brain and as long as his clients feel better when they leave, that is all that matters.

 

Just because tissue injury and structural damage does not correlate well with pain does not mean that they are completely irrelevant.  Imagine a runner with poor ankle dorsiflexion, poor glute strength, poor hip mobility, and other dysfunctions that increase his risk for damage to the knee joint. He goes to his chiropractor to treat his knee pain, and the chiropractor decides to focus all of his efforts towards treating the client’s pain rather than his ankle and hip dysfunction. After a few sessions of therapeutic neuroscience education, joint manipulations, and massage, the client is feeling less pain and decides to continue running regularly.

 

After many years, because the hip and ankle problems were never addressed, the knee continues to degrade to the point where severe osteoarthritis becomes present. At this point, no amount of psychosocial interventions are enough to reduce the pain he is feeling due to his injury, and now he has no choice but to have his knee replaced.

 

If his therapist had addressed his hip and ankle issues when he had first started feeling pain, it’s possible that the tissue damage would not have accelerated to this point. Unfortunately, an overemphasis on pain-reducing techniques can sometimes be harmful if it comes at the expense of treating movement dysfunction.

Conclusions

Pain and injury are two separate physiological phenomena. Pain can be present in the absence of injury and injury is often present in the absence of pain. Skilled clinicians must understand how to distinguish between the two and how to balance a treatment protocol to address both the pain and injury that their clients may be experiencing.

References

  1. Liu, T. C., Leung, N., Edwards, L., Ring, D., Bernacki, E., & Tonn, M. D. (2017). Patients Older Than 40 Years With Unilateral Occupational Claims for New Shoulder and Knee Symptoms Have Bilateral MRI Changes. Clinical Orthopaedics and Related Research®, 1-6.
  2. Borenstein, D. G., O’mara, J. W., Boden, S. D., Lauerman, W. C., Jacobson, A., Platenberg, C., … & Wiesel, S. W. (2001). The value of magnetic resonance imaging of the lumbar spine to predict low-back pain in asymptomatic subjects: a seven-year follow-up study. JBJS83(9), 1306-1311
  3. Brinjikji W, Luetmer PH, Comstock B, et al. Systematic literature review of imaging features of spinal degeneration in asymptomatic populations. AJNR Am J Neuroradiol. 2015;36(4):811-6
  4. Hitselberger, W. E., & Witten, R. M. (1968). Abnormal myelograms in asymptomatic patients. Journal of Neurosurgery28(3), 204-206.
  5. Jensen, M. C., Brant-Zawadzki, M. N., Obuchowski, N., Modic, M. T., Malkasian, D., & Ross, J. S. (1994). Magnetic resonance imaging of the lumbar spine in people without back pain. New England Journal of Medicine331(2), 69-73.
  6. van Tulder, M. W., Assendelft, W. J., Koes, B. W., & Bouter, L. M. (1997). Spinal radiographic findings and nonspecific low back pain: a systematic review of observational studies. Spine22(4), 427-434.
  7. Varkas, G., de Hooge, M., Renson, T., De Mits, S., Carron, P., Jacques, P., … & Van den Bosch, F. (2017). Effect of mechanical stress on magnetic resonance imaging of the sacroiliac joints: assessment of military recruits by magnetic resonance imaging study. Rheumatology.
  8. WeiShaupt, D., Zanetti, M., Hodler, J., & Boos, N. (1998). MR imaging of the lumbar spine: prevalence of intervertebral disk extrusion and sequestration, nerve root compression, end plate abnormalities, and osteoarthritis of the facet joints in asymptomatic volunteers. Radiology209(3), 661-666.
  9. Witwit, W. A., Kovac, P., Sward, A., Agnvall, C., Todd, C., Thoreson, O., … & Baranto, A. (2017). Disc degeneration on MRI is more prevalent in young elite skiers compared to controls. Knee Surgery, Sports Traumatology, Arthroscopy, 1-8.
  10. Bedson, J., & Croft, P. R. (2008). The discordance between clinical and radiographic knee osteoarthritis: A systematic search and summary of the literature. BMC Musculoskeletal Disorders9, 116. http://doi.org/10.1186/1471-2474-9-116\
  11. Edd, S. N., Favre, J., Blazek, K., Omoumi, P., Asay, J. L., & Andriacchi, T. P. (2017). Altered gait mechanics and elevated serum pro-inflammatory cytokines in asymptomatic patients with MRI evidence of knee cartilage loss. Osteoarthritis and cartilage25(6), 899-906.
  12. Englund, M., Guermazi, A., Gale, D., Hunter, D. J., Aliabadi, P., Clancy, M., & Felson, D. T. (2008). Incidental meniscal findings on knee MRI in middle-aged and elderly persons. New England Journal of Medicine359(11), 1108-1115.
  13. Matiotti, S. B., Soder, R. B., Becker, R. G., Santos, F. S., & Baldisserotto, M. (2017). MRI of the knees in asymptomatic adolescent soccer players: A case–control study. Journal of Magnetic Resonance Imaging45(1), 59-65.
  14. Paxinos, O., Karavasili, A., Delimpasis, G., & Stathi, A. (2016). Prevalence of knee osteoarthritis in 100 athletically active veteran soccer players compared with a matched group of 100 military personnel. The American journal of sports medicine44(6), 1447-1454.
  15. Girish, G., Lobo, L. G., Jacobson, J. A., Morag, Y., Miller, B., & Jamadar, D. A. (2011). Ultrasound of the shoulder: asymptomatic findings in men. American Journal of Roentgenology197(4), W713-W719.
  16. Tempelhof S, Rupp S, Seil R. Age-related prevalence of rotator cuff tears in asymptomatic shoulders. J Shoulder Elbow Surg. 1999;8(4):296-9.
  17. Milgrom, Charles & MB, Schaffler & Gilbert, S & van Holsbeeck, Marnix. (1995). Rotator-cuff changes in asymptomatic adults. The effect of age, hand dominance and gender. The Journal of bone and joint surgery. British volume. 77. 296-8.
  18. Schwartzberg, R., Reuss, B. L., Burkhart, B. G., Butterfield, M., Wu, J. Y., & McLean, K. W. (2016). High prevalence of superior labral tears diagnosed by MRI in middle-aged patients with asymptomatic shoulders. Orthopaedic journal of sports medicine4(1), 2325967115623212.
  19. Lederman, E. (2011). The fall of the postural-structural-biomechanical model in manual and physical therapies: exemplified by lower back pain. Journal of bodywork and movement therapies15(2), 131-138.
  20. Fritz, J. M., George, S. Z., & Delitto, A. (2001). The role of fear-avoidance beliefs in acute low back pain: relationships with current and future disability and work status. Pain94(1), 7-15.
  21. Leeuw, M., Goossens, M. E., Linton, S. J., Crombez, G., Boersma, K., & Vlaeyen, J. W. (2007). The fear-avoidance model of musculoskeletal pain: current state of scientific evidence. Journal of behavioral medicine30(1), 77-94.
  22. SUNI, D. (2017). BIO-PSYCHOSOCIAL FACTORS ARE ASSOCIATED WITH PAIN INTENSITY, PHYSICAL FUNCTIONING AND ABILITY TO WORK IN FEMALE HEALTHCARE PERSONNEL WITH RECURRENT LOW BACK PAIN. J Rehabil Med49, 667-676
  23. Waddell, G., Newton, M., Henderson, I., Somerville, D., & Main, C. J. (1993). A Fear-Avoidance Beliefs Questionnaire (FABQ) and the role of fear-avoidance beliefs in chronic low back pain and disability. Pain52(2), 157-168.
  24. Woby, S. R., Watson, P. J., Roach, N. K., & Urmston, M. (2004). Are changes in fear‐avoidance beliefs, catastrophizing, and appraisals of control, predictive of changes in chronic low back pain and disability?. European Journal of Pain8(3), 201-210.
  25. Briet, J. P., Houwert, R. M., Hageman, M. G., Hietbrink, F., Ring, D. C., & Verleisdonk, E. J. J. (2016). Factors associated with pain intensity and physical limitations after lateral ankle sprains. Injury47(11), 2565-2569.
  26. Cotchett, M., Lennecke, A., Medica, V. G., Whittaker, G. A., & Bonanno, D. R. (2017). The association between pain catastrophising and kinesiophobia with pain and function in people with plantar heel pain. The Foot.
  27. Cotchett, M., Munteanu, S. E., & Landorf, K. B. (2016). Depression, anxiety, and stress in people with and without plantar heel pain. Foot & ankle international, 37(8), 816-821.
  28. Chester, R., Jerosch-Herold, C., Lewis, J., & Shepstone, L. (2016). Psychological factors are associated with the outcome of physiotherapy for people with shoulder pain: a multicentre longitudinal cohort study. Br J Sports Med, bjsports-2016.
  29. Kazmers, N. H., Hung, M., Rane, A. A., Bounsanga, J., Weng, C., & Tyser, A. R. (2017). Association of Physical Function, Anxiety, and Pain Interference in Nonshoulder Upper Extremity Patients Using the PROMIS Platform. Journal of Hand Surgery42(10), 781-787.
  30. Wylie, J. D., Suter, T., Potter, M. Q., Granger, E. K., & Tashjian, R. Z. (2016). Mental health has a stronger association with patient-reported shoulder pain and function than tear size in patients with full-thickness rotator cuff tears. JBJS98(4), 251-256.
  31. Chehadi, O., Rusu, A. C., Konietzny, K., Schulz, E., Köster, O., Schmidt‐Wilcke, T., & Hasenbring, M. I. (2017). Brain structural alterations associated with dysfunctional cognitive control of pain in patients with low back pain. European Journal of Pain.
  32. Chehadi, O., Suchan, B., Konietzny, K., Köster, O., Schmidt-Wilcke, T., & Hasenbring, M. I. (2017). Gray matter alteration associated with pain catastrophizing in patients 6 months after lumbar disk surgery: a voxel-based morphometry study. Pain Reports2(5), e617.
  33. Curatolo, M., Petersen-Felix, S., Arendt-Nielsen, L., Giani, C., Zbinden, A. M., & Radanov, B. P. (2001). Central hypersensitivity in chronic pain after whiplash injury. The Clinical journal of pain17(4), 306-315.
  34. Flor, H., Braun, C., Elbert, T., & Birbaumer, N. (1997). Extensive reorganization of primary somatosensory cortex in chronic back pain patients. Neuroscience letters224(1), 5-8.
  35. François, A., Low, S. A., Sypek, E. I., Christensen, A. J., Sotoudeh, C., Beier, K. T., … & Delp, S. L. (2017). A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins. Neuron93(4), 822-839.
  36. Fukuoka, T., Tokunaga, A., Kondo, E., Miki, K., Tachibana, T., & Noguchi, K. (1998). Change in mRNAs for neuropeptides and the GABA A receptor in dorsal root ganglion neurons in a rat experimental neuropathic pain model. Pain78(1), 13-26.
  37. Kadowaki, M., Tadenuma, T., Kumahashi, N., & Uchio, Y. (2017). Brain Activity Changes in Somatosensory and Emotion-Related Areas With Medial Patellofemoral Ligament Deficiency. Clinical Orthopaedics and Related Research®475(11), 2675-2682.
  38. La Touche, R., Paris‐Alemany, A., Hidalgo‐Pérez, A., López‐de‐Uralde‐Villanueva, I., Angulo‐Diaz‐Parreño, S., & Muñoz‐García, D. (2017). Evidence for central sensitization in patients with temporomandibular disorders: a systematic review and meta‐analysis of observational studies. Pain Practice.
  39. Maihöfner, C., Handwerker, H. O., Neundörfer, B., & Birklein, F. (2003). Patterns of cortical reorganization in complex regional pain syndrome. Neurology61(12), 1707-1715.
  40. Moseley, G. L. (2004). Why do people with complex regional pain syndrome take longer to recognize their affected hand?. Neurology62(12), 2182-2186.
  41. Parker, R. S., Lewis, G. N., Rice, D. A., & McNair, P. J. (2016). Is motor cortical excitability altered in people with chronic pain? A systematic review and meta-analysis. Brain stimulation9
  42. Pas, R., Ickmans, K., Van Oosterwijck, S., Van der Cruyssen, K., Foubert, A., Leysen, L., … & Meeus, M. (2018). Hyperexcitability of the Central Nervous System in Children with Chronic Pain: A Systematic Review. Pain Medicine.
  43. Soon, B., Vicenzino, B., Schmid, A. B., & Coppieters, M. W. (2017). Facilitatory and inhibitory pain mechanisms are altered in patients with carpal tunnel syndrome. PloS one12(8), e0183252.
  44. Te, M., Baptista, A. F., Chipchase, L. S., & Schabrun, S. M. (2017). Primary Motor Cortex Organization Is Altered in Persistent Patellofemoral Pain. Pain Medicine, pnx036.
  45. Van Riper, S. M., Alexander, A. L., Koltyn, K. F., Stegner, A. J., Ellingson, L. D., Destiche, D. J., … & Cook, D. B. (2017). Cerebral white matter structure is disrupted in Gulf War Veterans with chronic musculoskeletal pain. Pain158(12), 2364-2375.
  46. Vuilleumier, P. H., Arguissain, F. G., Manresa, J. A. B., Neziri, A. Y., Nirkko, A. C., Andersen, O. K., … & Curatolo, M. (2017). Psychophysical and electrophysiological evidence for enhanced pain facilitation and unaltered pain inhibition in acute low back pain patients. The journal of pain18(11), 1313-1323.
  47. Woolf, C. J. (2007). Central sensitizationuncovering the relation between pain and plasticity. Anesthesiology: The Journal of the American Society of Anesthesiologists106(4), 864-867.
  48. Woolf, C. J., & Doubell, T. P. (1994). The pathophysiology of chronic pain—increased sensitivity to low threshold Aβ-fibre inputs. Current opinion in neurobiology4(4), 525-534.
  49. Bialosky, J. E., Bishop, M. D., & Cleland, J. A. (2016). Individual expectation: an overlooked, but pertinent, factor in the treatment of individuals experiencing musculoskeletal pain. Physical therapy90(9), 1345-1355.
  50. Cormier, S., Lavigne, G. L., Choinière, M., & Rainville, P. (2016). Expectations predict chronic pain treatment outcomes. Pain157(2), 329-338.
  51. Gollub, R. L., Kirsch, I., Maleki, N., Wasan, A. D., Edwards, R. R., Tu, Y., … & Kong, J. (2018). A Functional Neuroimaging Study of Expectancy Effects on Pain Response in Patients with Knee Osteoarthritis. The Journal of Pain.
  52. Puentedura, E. J., Cleland, J. A., Landers, M. R., Mintken, P., Louw, A., & Fernández-de-las-Peñas, C. (2012). Development of a clinical prediction rule to identify patients with neck pain likely to benefit from thrust joint manipulation to the cervical spine. journal of orthopaedic & sports physical therapy42(7), 577-592.
  53. Wager, T. D., Rilling, J. K., Smith, E. E., Sokolik, A., Casey, K. L., Davidson, R. J., … & Cohen, J. D. (2004). Placebo-induced changes in FMRI in the anticipation and experience of pain. Science303(5661), 1162-1167.
  54. Brown, J. L., Sheffield, D., Leary, M. R., & Robinson, M. E. (2003). Social support and experimental pain. Psychosomatic medicine65(2), 276-283.
  55. Che, X., Cash, R., Fitzgerald, P., & Fitzgibbon, B. M. (2017). The Social Regulation of Pain: Autonomic and Neurophysiological Changes Associated with Perceived Threat. The Journal of Pain.
  56. Coan, J. A., Schaefer, H. S., & Davidson, R. J. (2006). Lending a hand: Social regulation of the neural response to threat. Psychological science17(12), 1032-1039.
  57. Eisenberger, N. I., Master, S. L., Inagaki, T. K., Taylor, S. E., Shirinyan, D., Lieberman, M. D., & Naliboff, B. D. (2011). Attachment figures activate a safety signal-related neural region and reduce pain experience. Proceedings of the National Academy of Sciences108(28), 11721-11726.
  58. Johnson, K. V. A., & Dunbar, R. I. (2016). Pain tolerance predicts human social network size. Scientific reports6.
  59. Master, S. L., Eisenberger, N. I., Taylor, S. E., Naliboff, B. D., Shirinyan, D., & Lieberman, M. D. (2009). A picture’s worth: Partner photographs reduce experimentally induced pain. Psychological Science20(11), 1316-1318.
  60. Sambo, C. F., Howard, M., Kopelman, M., Williams, S., & Fotopoulou, A. (2010). Knowing you care: effects of perceived empathy and attachment style on pain perception. PAIN®151(3), 687-693.
  61. Shaygan, M., Böger, A., & Kröner-Herwig, B. (2017). Valence and arousal value of visual stimuli and their role in the mitigation of chronic pain: What is the power of pictures?. The Journal of Pain18(2), 124-131.
  62. Younger, J., Aron, A., Parke, S., Chatterjee, N., & Mackey, S. (2010). Viewing pictures of a romantic partner reduces experimental pain: Involvement of neural reward systems. PloS one5(10), e13309.
  63. Egbert, L. D., Battit, G. E., Welch, C. E., & Bartlett, M. K. (1964). Reduction of postoperative pain by encouragement and instruction of patients: a study of doctor-patient rapport. New England Journal of Medicine270(16), 825-827.
  64. Fuentes, J., Armijo-Olivo, S., Funabashi, M., Miciak, M., Dick, B., Warren, S., … & Gross, D. P. (2014). Enhanced therapeutic alliance modulates pain intensity and muscle pain sensitivity in patients with chronic low back pain: an experimental controlled study. Physical therapy94(4), 477-489.
  65. Lakke, S. E., & Meerman, S. (2016). Does working alliance have an influence on pain and physical functioning in patients with chronic musculoskeletal pain; a systematic review. Journal of Compassionate Health Care3(1), 1.
  66. Losin, E. A. R., Anderson, S. R., & Wager, T. D. (2017). Feelings of Clinician-Patient Similarity and Trust Influence Pain: Evidence From Simulated Clinical Interactions. The Journal of Pain.
  67. Ruben, M. A., Meterko, M., & Bokhour, B. G. (2017). Do patient perceptions of provider communication relate to experiences of physical pain?. Patient education and counseling.
  68. Beltran-Alacreu, H., López-de-Uralde-Villanueva, I., Fernández-Carnero, J., & La Touche, R. (2015). Manual therapy, therapeutic patient education, and therapeutic exercise, an effective multimodal treatment of nonspecific chronic neck pain: a randomized controlled trial. American Journal of Physical Medicine & Rehabilitation94(10S), 887-897.
  69. Brage, K., Ris, I., Falla, D., Søgaard, K., & Juul-Kristensen, B. (2015). Pain education combined with neck-and aerobic training is more effective at relieving chronic neck pain than pain education alone–A preliminary randomized controlled trial. Manual therapy20(5), 686-693
  70. Frederiksen, P., Indahl, A., Andersen, L. L., Burton, K., Hertzum-Larsen, R., & Bendix, T. (2017). Can group-based reassuring information alter low back pain behavior? A cluster-randomized controlled trial. PloS one12(3), e0172003.
  71. Louw, A., Diener, I., Butler, D. S., & Puentedura, E. J. (2011). The effect of neuroscience education on pain, disability, anxiety, and stress in chronic musculoskeletal pain. Archives of physical medicine and rehabilitation92(12), 2041-2056.
  72. Louw, A., Zimney, K., Johnson, E. A., Kraemer, C., Fesler, J., & Burcham, T. (2017). De-educate to re-educate: aging and low back pain. Aging Clinical and Experimental Research, 1-9.
  73. Malfliet, A., Kregel, J., Meeus, M., Roussel, N., Danneels, L., Cagnie, B., … & Nijs, J. (2017). Blended-Learning Pain Neuroscience Education for People With Chronic Spinal Pain: Randomized Controlled Multicenter Trial. Physical Therapy.
  74. Moseley, G. L. (2003). Joining forces–combining cognition-targeted motor control training with group or individual pain physiology education: a successful treatment for chronic low back pain. Journal of Manual & Manipulative Therapy11(2), 88-94.
  75. Moseley, G. L. (2004). Evidence for a direct relationship between cognitive and physical change during an education intervention in people with chronic low back pain. European Journal of Pain8(1), 39-45.
  76. Moseley, G. L., Nicholas, M. K., & Hodges, P. W. (2004). A randomized controlled trial of intensive neurophysiology education in chronic low back pain. The Clinical journal of pain20(5), 324-330.
  77. Oliveira, A., Gevirtz, R., & Hubbard, D. (2006). A psycho-educational video used in the emergency department provides effective treatment for whiplash injuries. Spine31(15), 1652-1657.
  78. Puentedura, E. J., & Flynn, T. (2016). Combining manual therapy with pain neuroscience education in the treatment of chronic low back pain: A narrative review of the literature. Physiotherapy theory and practice32(5), 408-414.
  79. Ryan, C. G., Gray, H. G., Newton, M., & Granat, M. H. (2010). Pain biology education and exercise classes compared to pain biology education alone for individuals with chronic low back pain: a pilot randomised controlled trial. Manual therapy15(4), 382-387.
  80. Van Oosterwijck, J., Nijs, J., Meeus, M., Truijen, S., Craps, J., Van den Keybus, N., & Paul, L. (2011). Pain neurophysiology education improves cognitions, pain thresholds, and movement performance in people with chronic whiplash: a pilot study. Journal of rehabilitation research and development48(1), 43-58