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Assessment of mechanisms in localized and widespread musculoskeletal pain


The aim of this Review is to give a short presentation of the manifestations, assessment methods, and mechanisms underlying localized and widespread musculoskeletal pain, deep somatic tissue hyperalgesia and chronification. Hyperalgesia can be explained by increased pain sensitivity of nociceptors located in deep tissue (peripheral sensitization) or by increased responses from dorsal horn neurons (central sensitization). The spreading of pain and sensitization is related to increased synaptic activity in central neurons and to changes in descending control from supraspinal centers. Manifestations related to the different aspects of sensitization can be assessed quantitatively using sensory tests, such as pressure algometry (quantitative palpation) and cuff-algometry. Repeated pressure stimulation can evaluate the degree of temporal summation, which is a proxy for the level of central sensitization, as is expanded referred muscle pain area. The transition of acute localized musculoskeletal pain into chronic widespread pain is related to the progression of peripheral and central sensitization. This sensitization for the chronification of pain should be assessed by adequate pain biomarkers. Furthermore, pain prevention should target early intervention strategies and new anti-hyperalgesic compounds should be developed.

Key Points

  • The different manifestations of localized, regional and widespread musculoskeletal pain involve different peripheral and central mechanisms

  • Methodologies are available for quantitative assessment of musculoskeletal pain targeting specific mechanisms such as hyperalgesia, spreading sensitization, temporal summation and pain referral

  • Peripheral and central sensitization are key neurophysiologic mechanisms in musculoskeletal pain

  • Central sensitization is a likely reason for the chronification of widespread pain conditions

  • The transition of acute localized musculoskeletal pain into chronic widespread pain is probably related to the progression of peripheral and central sensitization

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Figure 1: Distribution of ongoing pain in patients with whiplash pain presented as an example of a widespread pain condition.
Figure 2: Examples of normal and abnormal referred pain patterns in patients with musculoskeletal pain.
Figure 3: Hypothetical model explaining the transition from localized pain caused by tissue damage to a widespread pain condition.


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T. Graven-Nielsen & L. Arendt-Nielsen researched the data for the article, provided a substantial contribution to discussions of the content, and contributed equally to writing, reviewing and editing the manuscript before submission.

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Correspondence to Thomas Graven-Nielsen.

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Graven-Nielsen, T., Arendt-Nielsen, L. Assessment of mechanisms in localized and widespread musculoskeletal pain. Nat Rev Rheumatol 6, 599–606 (2010).

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