Research Review By Dr. Brynne Stainsby©


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Date Posted:

December 2016

Study Title:

The role of spinal manipulation in modifying central sensitization


Zafereo JA & Deschenes BK

Author's Affiliations:

Department of Physical Therapy, University of Texas Southwestern, Dallas, TX, USA.

Publication Information:

Journal of Applied Biobehavioral Research 2015; 20: 84-99.

Background Information:

The concept of pain perception has garnered significant clinical and research attention in recent decades, the mechanisms of which are now understood to involve very complex interactions among supraspinal centres, the spinal cord and peripheral nociceptors (1-3) – essentially all major components of the nervous system!

It has been hypothesized that plastic changes in the spinal cord and brain may lead to pain perpetuation. Plastic changes and the concept of brain plasticity may be novel to some, but it refers to the ability of the brain to undergo changes, whether good or bad, at any age. This is foundational to the concept of central sensitization (CS) (4). In poorly understood conditions such as fibromyalgia, chronic regional pain syndrome or chronic musculoskeletal pain conditions, it is possible (or likely!) that CS is contributing to the clinical presentation (4).

The development of CS has been associated with adaptation of the central nervous system (CNS). At the level of the dorsal horn neurons, temporal summation creates a progressive increase in the perceived intensity of a stimulus, which can result in a decreased sensory threshold for pain perception, hypersensitivity and allodynia (5, 6). At the supraspinal level, pain perception may be magnified at the thalamus or other centres, and lead to abnormal afferent input to the somatosensory cortex (1, 2). This may result in altered sensorimotor integration, impaired movement, altered motor control, and perhaps pain (7). It is also possible that psychological conditions could magnify pain perception by affecting the midbrain, specifically the periaqueductal gray area (PAG) (3).

The management of these very complex pain experiences typically aims to address central and peripheral nociception, often involving a combination of medication, pain education, cognitive behavioural therapy and exercise interventions (3). The role of spinal manipulative therapy (SMT) in these cases has not been well studied to date, but given the growing body of knowledge regarding the neurophysiological effects of SMT, it is possible that by affecting the CNS, SMT could be a useful intervention in combatting CS (1). The authors of this narrative review discussed the literature pertaining to the potential of SMT to positively influence CS.

Pertinent Results:

Over 100 abstracts were assessed, with 42 articles and one textbook included for review.

General Summary Points:
  • The mechanistic studies included in this review suggested that SMT and CS may affect similar regions of the CNS.
  • Neurophysiological changes with SMT and CS have been observed in the dorsal horn of the spinal cord, the periaqueductal gray (PAG – the primary control centre for descending pain inhibition) and the cerebral cortex, thus supporting the hypothesis that SMT may alter centrally-mediated pain (1, 7-10).
  • These studies have demonstrated regional mechanical hypoalgesia, and changes in sympathetic nervous system (SNS) function, spinal cord hyperexcitability, sensorimotor integration and motor control following manipulation (1, 7-10).
  • While CS has been found to disrupt descending pain pathway inhibition and SNS function, SMT appears to positively impact the midbrain (and thus these same pathways), perhaps helping to explain the regional mechanical hypoalgesia seen with SMT (11).
  • Following SMT, local (segmental) reductions in pain pressure thresholds support the role of spinal cord responses in altering pain perception (9, 10, 12). It is important to note that these changes have occurred caudal to the manipulated region (8).
  • Although results have not been consistent, it has also been proposed that SMT may elicit a sympathoexcitatory response from the PAG, which may further inhibit pain perception and alter physiological function (10, 13-18).
  • It has also been suggested that the ability of SMT to improve somatosensory processing and proprioceptive integration may indirectly decrease pain through improved postural control, further supporting the role of the cortex contributing to the sensory and motor effects of manipulation (7).

Clinical Application & Conclusions:

This study suggested numerous conditions that can include some component of central sensitization, and thus may respond favorably to SMT, specifically:
  • Fibromyalgia
  • Chronic regional pain syndrome
  • Chronic whiplash-associated disorders
  • Lateral epicondylitis
  • Temporomandibular disorders
Unfortunately, the literature related to the use of manipulation for these conditions is either limited to case studies, or controlled trials that resulted in generally inconclusive evidence due to methodological flaws (4, 19-26).

Having said that, it is very important to consider that the patient’s pain threshold may affect their individual response to manual treatment (including SMT). As many of you have seen in practice, not all patients with CS will respond favourably to high-velocity, low amplitude manipulation. It is therefore important for clinicians to consider the physical and psychological status of the patient, and the type, location, duration and intensity of treatment in an attempt to maximize positive outcomes. The authors suggest that clinicians should attempt to test the patient’s tolerance to non-thrust techniques before introducing a thrust, particularly if treating the painful area. This seems like reasonable advice, especially for patients who may have chronic pain or be particularly pain sensitive (or, in other words, centrally sensitized).

Study Methods:

This was a narrative literature review that lacked a clearly reported methodology. A literature search was performed in PubMed and CINAHL between July and September 2013 using MeSH or CINAHL headings respectively. The authors specifically searched for articles related to manipulation, pain, chronic pain and terms related to central sensitization. No information was provided about article screening or appraisal or data extraction.

Study Strengths / Weaknesses:

  • This review summarized theoretical constructs related to the neurophysiological effects of spinal manipulation in a well-organized, well described manner.
  • The authors reviewed the neuroanatomy and neurophysiology of the structures and systems related to pain perception and SMT.
  • A number of hypotheses were presented to describe how the nervous system may respond to SMT.
  • A number of clinical conditions relating to or potentially caused by CS were included.
  • The greatest weakness of this study is the lack of methodology reported. Without this, we cannot be confident that the results and conclusions were not subject to some degree of bias.
  • The authors did not report if or how the included articles were appraised. While evidence is occasionally referred to as “weak” or “strong”, without assessment of quality, we cannot interpret these statements in a rigorous, research-based context.
  • While this article provided a summary of the literature included, there is no assessment of the methodology or research quality. We have no knowledge of randomization and allocation concealment, reporting of co-intervention and reasons for dropout, selective reporting of results, and reporting on adherence.
  • There was no comment on the participants or clinical settings of the included studies, thus limiting the external validity of the review.

Additional References:

  1. Bialosky JE, Bishop MD, Price DD, et al. The mechanisms of manual therapy in the treatment of musculoskeletal pain: A comprehensive model. Manual Therapy 2009; 14: 531–538.
  2. Bingham B, Ajit SK, Blake DR, et al. The molecular basis of pain and its clinical implications in rheumatology. Nat Clin Pract Rheumatol 2009; 5: 28–37.
  3. Nijs J, Van Houdenhove B. From acute musculoskeletal pain to chronic widespread pain and fibromyalgia: Application of pain neurophysiology in manual therapy practice. Manual Therapy 2009; 14: 3–12.
  4. Woolf CJ. Central sensitization: Implications for the diagnosis and treatment of pain. Pain 2011; 152 (3 Suppl): S2–15.
  5. Herrero JF, Laird JM, Lopez-Garcia JA. Wind-up of spinal cord neurones and pain sensation: Much ado about something? Prog Neurobio 2000; 61: 169–203.
  6. George SZ, Bishop MD, Bialosky JE et al. Immediate effects of spinal manipulation on thermal pain sensitivity: An experimental study. BMC Musculoskelet Disord 2006; 7: 68.
  7. Haavik H, Murphy B. The role of spinal manipulation in addressing disordered sensorimotor integration and altered motor control. J Electromyogr Kines 2012; 22: 768–776.
  8. Bishop MD, Beneciuk, JM, George SZ. Immediate reduction in temporal sensory summation after thoracic spinal manipulation. Spine 2011; 11: 440–446.
  9. Coronado RA, Gay CW, Bialosky JE et al. Changes in pain sensitivity following spinal manipulation: A systematic review and meta-analysis. J Electromyogr Kines 2012; 22: 752–767.
  10. Schmid A, Brunner F, Wright A et al. Paradigm shift in manual therapy? Evidence for a central nervous system component in the response to passive cervical joint mobilisation. Manual Ther 2008; 13: 387–396.
  11. Olson KA. Manipulation: Theory, practice, and education. Manual Physical Therapy of the Spine 2009; St. Lois, MO: Saunders. pp 76-78.
  12. Srbely JZ, Vernon H, Lee D et al. Immediate effects of spinal manipulative therapy on regional antinociceptive effects in myofascial tissues in healthy young adults. J Manipulative Physiol Ther 2013; 36: 333–341.
  13. Moulson A, Watson T. A preliminary investigation into the relationship between cervical snags and sympathetic nervous system activity in the upper limbs of an asymptomatic population. Manual Ther 2006; 11: 214–224.
  14. Perry J, Green A. An investigation into the effects of a unilaterally applied lumbar mobilisation technique on peripheral sympathetic nervous system activity in the lower limbs. Manual Ther 2008; 13: 492–499.
  15. Perry J, Green A, Singh S et al. A preliminary investigation into the magnitude of effect of lumbar extension exercises and a segmental rotatory manipulation on sympathetic nervous system activity. Manual Ther 2011; 16: 190–195.
  16. Sterling M, Pedler A, Chan C et al. Cervical lateral glide increases nociceptive flexion reflex threshold but not pressure or thermal pain thresholds in chronic whiplash disorders: A pilot randomized controlled trial. Manual Ther 2010; 15: 149-153.
  17. Puhl AA, Injeyan HS. Short-term effects of manipulation to the upper thoracic spine of asymptomatic subjects on plasma concentrations of epinephrine and norepinephrine-a randomized and controlled observational study. J Manipulative Physiol Ther 2012; 35: 209–215.
  18. Sillevis R, Cleland J, Hellman M et al. Immediate effects of a thoracic spine thrust manipulation on the autonomic nervous system: A randomized clinical trial. J Man Manip Ther 2010; 18: 181–190.
  19. Nijs J, Van Houdenhove B, Oostendorp RA. Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice. Manual Ther 2010: 15: 135–141.
  20. Schneider M, Vernon H, Ko G et al. Chiropractic management of fibromyalgia syndrome: A systematic review of the literature. J Manipulative Physiol Ther 2009; 32: 25–40.
  21. Ernst E. Chiropractic treatment for fibromyalgia: A systematic review. Clin Rheumatol 2009; 28: 1175–1178.
  22. Beck RW. Conservative therapy for complex regional pain syndrome type I in a paediatric patient: A case study. J Can Chiropr Assoc 2009; 53: 95–101.
  23. Menck JY, Requejo SM, Kulig K. Thoracic spine dysfunction in upper extremity complex regional pain syndrome type I. J Orthop Sports Phys 2000; 30: 401–409.
  24. Lowry CD, O’Hearn MA, Courtney CA. Resolution of whiplash-associated allodynia following cervicothoracic thrust and nonthrust manipulation. Physiother Theory Pract 2011; 27: 451–459.
  25. Fernandez-Carnero J, Cleland JA, Arbizu RL. Examination of motor and hypoalgesic effects of cervical vs thoracic spine manipulation in patients with lateral epicondylalgia: A clinical trial. J Manipulative Physiol Ther 2011; 34: 432–440.
  26. Fernandez-Carnero J, Fernandez-de-las-Penas C, Cleland JA. Immediate hypoalgesic and motor effects after a single cervical spine manipulation in subjects with lateral epicondylalgia. J Manipulative Physiol Ther 2008; 31: 675–681.