Research Review By Gary Maguire©


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Date Posted:

December 2010

Study Title:

Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice


Nijs J et al.

Author's Affiliations:

Department of Human Physiology, Faculty of Physical Education & Physiology, Vrije Universiteit Brussels, Belgium.

Publication Information:

Manual Therapy 2010; 15: 135-141.

Background Information:

Central sensitization is defined as an augmentation of central neuron responsiveness to input from unimodal and polymodal receptors. Central sensitization encompasses:
  • malfunctioning of descending anti-nociceptive mechanisms
  • increased activity of pain facilitation pathways
  • altered sensory processing in the brain
  • temporal summation of sequential pain signals (or “wind-up”)
  • long term potentiation of neuronal synapses in the anterior cingulate cortex
Aside from these “top-down” mechanisms included in the pathophysiology of central sensitization, it is important to remember that there are “bottom-up” mechanisms as well. For example, peripheral injury and other stressors trigger the release of pro-inflammatory cytokines, with subsequent activation of spinal cord glia, leading to expression of cyclooxygenase-2 and prostaglandin E2.

The outcome of these processes is an increased responsiveness to a variety of peripheral stimuli including mechanical pressure, light, sound, chemical substances, cold, heat, and electrical stimuli. The increased sensitivity to multiple stimuli results in a reduced load tolerance of the senses and the neuromusculoskeletal system in general.

Central sensitization is frequently present in a variety of chronic musculoskeletal pain disorders, including (but not limited to):
  • chronic whiplash associated disorders
  • temporomandibular disorders
  • chronic low back pain
  • rheumatoid arthritis
  • various types of headache (including migraine and tension)
  • fibromyalgia
Clinicians should be aware of the potential presence of central sensitization in patients with musculoskeletal pain as it results in an increased complexity of the overall clinical picture (i.e. an increase in unrelated symptoms and hence a more difficult clinical reasoning process) (1).

We should also be aware that even with acute pain, the nervous system undergoes some changes. When tissue is damaged and pain persists for a few days, unimodal nociceptors adapt, which augments the responsiveness of polymodal nociceptive endings to substances released from various sources (i.e. serotonin released by platelets). This process is called primary hyperalgesia or peripheral sensitization of nociceptors, and represents a protective action by the human body in order to prevent further use of damaged structures as well as subsequent further damage of the traumatized and surrounding tissues.

Secondary hyperalgesia refers to increased responsiveness of dorsal horn neurons localized in the spinal segments of the primary source of nociception. While peripheral sensitization is a local phenomenon, central sensitization is a central process of the nervous system.

Currently an international consensus on the definition or criteria for diagnosing central sensitization is essentially lacking. There is however, a body of scientific literature reporting original data on signs and symptoms related to established measures of central sensitization in patients with musculoskeletal pain that is currently available.

Application of our current understanding of central sensitization in the clinical assessment of patients with musculoskeletal pain will allow manual therapists to apply the science of pain neurophysiology to the practice of manual therapy.

Pertinent Information:

“Central sensitivity syndromes” was first used by Yunus in 2000 to describe a group of overlapping conditions bound by a common pathophysiological mechanism - central sensitization (2). Using the body of literature available linking medical diagnoses to central sensitization this concept can be applied to manual therapy practice. For example, in fibromyalgia and chronic fatigue syndrome the medical diagnosis most often implies the presence of central sensitization.

Many medical diagnoses are associated but not uniformly characterized by central sensitization. Therefore, the clinician should be aware of the possibility that central sensitization may or may not be present. History taking is the first key step that is necessary to recognize central sensitization. The presence of central sensitization within the central nervous system entails much more than generalized hypersensitivity to pain: it is characterized by an increased responsiveness to a variety of stimuli including mechanical pressure, chemical substances, cold temperature, electrical stimuli, stress, emotions and mental load.

The overall clinical picture is suggestive of a general intolerance to all kinds of physical and emotional stressors; a decreased load tolerance of the human body in general. Examples of hypersensitivity are: a hug by a partner being painful, wearing sunglasses indoors and turning down the radio even when it is already at a low volume level. In addition, less obvious symptoms may also be related to central sensitization but lack supporting evidence (e.g. fatigue, concentration difficulties and sleep disturbances).

It is suggested that when two or three of the “hypersensitivity” symptoms are present, further investigation via clinical examination is warranted to look for additional indicators of central sensitization. Even in the absence of a medical diagnosis known to be related to central sensitization, such signs should alert the manual therapist.

The presence of a local pain condition prior to the onset of trauma or injury increases the probability for developing peripheral and central sensitization. Another factor to consider is that tissue injury healing and focal pain recovery should occur as soon as possible to prevent development of central sensitization. Emphasis is focused on questioning the patient about the disease course, recovery course and premorbid medical conditions which provide important information for the clinician in relation to central sensitization.

Clinical Examination:

When central sensitization is suspected based on the medical diagnosis and/or the information gathered in the patient history, the manual therapist may wish to examine the patient’s response to certain stimuli. Sensory testing can be used to assess the presence or severity of sensitization, and monitor pre versus post-treatment progression to determine the appropriate treatment parameters (e.g. intensity, amplitude and frequency of various manual therapy techniques).

One of the main characteristics of central sensitization in patients with musculoskeletal pain is a generalized rather than a localized decrease in their pressure pain threshold. This is defined as increased sensitivity that is generally unrelated to the primary source of nociception (e.g. the lower limbs in case of a whiplash trauma). By measuring pressure pain thresholds outside the area of primary nociception, widespread hyperalgesia or secondary hyperalgesia can be detected.

Findings of numerous areas of hyperalgesia at sites outside and remote from the symptomatic site, together with a non-segmental general decrease in pressure pain threshold may imply a generalized hyperexcitability of the central nociceptive pathways. Assessment can be obtained utilizing a pressure algometer or manual palpation which should alert the clinician and provide documentation.

Hypersensitivity to other stimuli can be demonstrated clinically by using a cold or hot item. The patient should be able to identify the perceived temperature of the item, but this should not elicit pain. The use of mechanical stimulation like vibration at sites remote from the primary source of nociception can also generate important information addressing general sensitization. Other tests such as bilateral responses to the brachial plexus provocation tests have also been proposed as a sign of central sensitization in patient with chronic whiplash associated disorders (3).

Other tests that could be included in the assessment are: Pain provocation during neurodynamic testing, range of motion noting the onset of pain, investigating for submaximal pain with limited elbow extension (~30°) and muscle and joint end feel testing can all be performed and interpreted as part of the whole clinical picture when making an assessment of central sensitization.

Altered sensory processing can also be determined during exercise. Normally, pain thresholds increase during physical activity in healthy individuals and can stay augmented for up to 30 minutes post-exercise. In some chronic pain populations, these anti-nociception mechanisms cannot respond to the exercise stimulus in this manner. However, in subjects with chronic low back pain, pain thresholds often increase normally in response to exercises indicating that we cannot generalize the finding of deregulated anti-nociceptive mechanisms to all chronic pain populations.

We should also remember that stress (particularly when chronic) may trigger lower pain thresholds. Overall, this can be measured using a variety of tests. In general, an abnormal pain threshold response to exercise should be regarded as one of the many possible signs of central sensitization.

Clinical Assessment:

In some cases of musculoskeletal pain, the process of central sensitization is not present at the time of treatment initiation, but becomes apparent during the rehabilitation process. This is most often the case when physical and emotional stressors combine, resulting in an overall load that is beyond the load tolerance of the individual patient. Manual therapy interventions aim to increase a patient’s load tolerance but can also become a stressor themselves due to the patient’s hypersensitivity.

When new symptoms appear during the treatment course, existing symptoms may be aggravated and/or expand, even to sites outside and remote form the symptomatic site. It is important to monitor and differentiate referred sensations from the onset of new symptoms. Manual therapists should also consider central sensitization in cases of poor treatment progress or in the case of significant increases in symptom severity post-treatment (beyond what might normally be expected).

It should also be noted that even during treatment, the patient with central sensitization may respond differently: if central sensitization is present then pain thresholds may decrease further during the use of high intensity hands-on treatment. This is a clinical sign of the inability of the descending anti-nociceptive pathways to suppress temporal summation or wind-up in patients with central sensitization.

The diagnosis of central sensitization in individual patients with musculoskeletal pain is not straightforward. Manual therapists can use information obtained from the medical diagnosis, patient history, clinical examination and the analysis of treatment response to recognize central sensitization and determine the appropriate treatment parameters (e.g. intensity and frequency of various techniques).

Study Strengths / Weaknesses:

The authors acknowledge that the above manuscript regarding the understanding of central sensitization was inspired by attending an annual seminar of the Norwegian Manual Therapy Association (Oslo, February 2009). This acknowledgement validates the lack of clarity in providing stronger evidence and published findings to support the analysis portion of the manuscript.

Central sensitization is an important consideration with manual therapy treatment application, exacerbation of symptoms or lack of progress with a treatment plan applied to a particular condition, particularly in cases of difficult and poorly understood neuromuscular conditions such as fibromyalgia and complex regional pain syndrome (previously reflex sympathetic dystrophy).

The manuscript would have been strengthened by focusing more on the nervous system and what differentiates peripheral sensitization as a local phenomenon and central sensitization as a central process of the nervous system.

The strength of the manuscript is that it raises awareness of this poorly understood pathophysiology that develops within numerous musculoskeletal pain disorders. Further research is needed as pointed out by the authors to provide mechanism-based clinical guidelines for the recognition, understanding and treatment of central sensitization.

Clinicians need to be aware that long standing symptoms can lead to central sensitization and the authors of this manuscript have provided some initial guidelines to utilize during patient history taking, clinical examination, assessment and patient treatment response.

Additional References:

  1. Nils J et al. From acute musculoskeletal pain to chronic widespread pain and fibromyalgia: application of pain neurophysiology in manual therapy practice. Manual Therapy 2009; 14: 3-12.
  2. Yunus MB. Central sensitivity syndromes: a unified concept for fibromyalgia and other similar maladies. Journal of Indian Rheumatism Association 2000; 8:27-33.
  3. Scott D et al. Widespread sensory hypersensitivity is a feature of chronic whiplash-associated disorder but not chronic idiopathic neck pain. Clin J Pain 2005; 21: 175-181.
  4. Prushansky T et al. Reproducibility indices applied to cervical pressure pain threshold measurements in healthy subjects. Clin J Pain 2004; 20: 341-347.
  5. Sterling M and Kenardy J. Physical and psychological aspects of whiplash: important considerations for primary care assessment. Manual Therapy 2008; 13:93-102.