Spinal mechanisms contributing to joint pain. N-methyl- D-aspartate (NMDA) and non-NMDA receptor antagonists block the hyperexcitability of dorsal horn neurons during development of acute arthritis in rat's knee joint. The sources of pain in knee osteoarthritis. Reactivity to superficial and deep stimuli in patients with chronic musculoskeletal pain. Report of the multicenter criteria committee. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Myofascial Pain and Dysfunction: the Trigger Point Manual (Lippincott Williams & Wilkins, Philadelphia, 1999). Observations on referred pain arising from muscle. Fundamentals of muscle pain, referred pain, and deep tissue hyperalgesia. Muscle Pain: Understanding Its Nature, Diagnosis, and Treatment (Lippincott Williams & Wilkins, Philadelphia, 2001). Recognition of central sensitization in patients with musculoskeletal pain: application of pain neurophysiology in manual therapy practice. Clinical indicators of 'nociceptive', 'peripheral neuropathic' and 'central' mechanisms of musculoskeletal pain. Furthermore, pain prevention should target early intervention strategies and new anti-hyperalgesic compounds should be developed. This sensitization for the chronification of pain should be assessed by adequate pain biomarkers. The transition of acute localized musculoskeletal pain into chronic widespread pain is related to the progression of peripheral and central sensitization. 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. Manifestations related to the different aspects of sensitization can be assessed quantitatively using sensory tests, such as pressure algometry (quantitative palpation) and cuff-algometry. The spreading of pain and sensitization is related to increased synaptic activity in central neurons and to changes in descending control from supraspinal centers. 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 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.
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