Central hypersensitivity in chronic pain: mechanisms and clinical implications

Phys Med Rehabil Clin N Am. 2006 May;17(2):287-302. doi: 10.1016/j.pmr.2005.12.010.


The available literature consistently shows increased pain sensitivity after sensory stimulation of healthy tissues in patients who have various chronic pain conditions. This indicates a state of hypersensitivity of the CNS that amplifies the nociceptive input arising from damaged tissues. Experimental data indicate that central hypersensitivity is probably induced primarily by nociceptive input arising from a diseased tissue. In patients, imbalance of descending modulatory systems connected with psychologic distress may play a role. There is experimental support in animal studies for the persistence of central hypersensitivity after complete resolution of tissue damage. This is particularly true for neuropathic pain conditions, whereby potentially irreversible plasticity changes of the CNS have been documented in animal studies. Whether such changes are present in musculoskeletal pain states is at present uncertain. Despite the likely importance of central hypersensitivity in the pathophysiology of chronic pain, this mechanism should not be used to justify the lack of understanding on the anatomic origin of the pain complaints in several pain syndromes, which is mostly due to limitations of the available diagnostic tools. Treatment strategies for central hypersensitivity in patients have been investigated mostly in neuropathic pain states. Possible therapy modalities for central hypersensitivity in chronic pain of musculoskeletal origin are largely unexplored. The limited evidence available and everyday practice show, at best, modest efficacy of the available treatment modalities for central hypersensitivity. The gap between basic knowledge and clinical benefits remains large and should stimulate further intensive research.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Central Nervous System / physiopathology*
  • Chronic Disease
  • Electromyography
  • Female
  • Humans
  • Hyperalgesia / etiology*
  • Hyperalgesia / physiopathology
  • Hyperalgesia / rehabilitation
  • Male
  • Pain / complications*
  • Pain / diagnosis
  • Pain / rehabilitation*
  • Pain Measurement
  • Pain Threshold
  • Prognosis
  • Reference Values
  • Risk Assessment
  • Sensory Thresholds
  • Spinal Cord Injuries / diagnosis