Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia)

Pain. 2006 Oct;124(3):242-263. doi: 10.1016/j.pain.2006.06.001. Epub 2006 Jul 13.


Chronic fibromyalgia (FM) pain is prevalent (estimated as high as 13%), predominantly affects women, and is associated with a variety of focal pain conditions. Ongoing FM pain is referred to deep tissues and is described as widespread but usually is maximally located within a restricted region such as the shoulders. Palpation of deep tissues reveals an enhanced nociceptive sensitivity that is not restricted to regions of clinical pain. Similarly, psychophysical testing reveals allodynia and hyperalgesia for cutaneous stimulation at locations beyond regions of clinical pain referral. The combination of widely distributed clinical pain and generalized hypersensitivity is highly disabling, but no satisfactory treatment is regularly prescribed. A thorough understanding of mechanisms will likely be required to develop and document adequate therapies. The generalized hypersensitivity associated with FM has focused considerable interest on central (CNS) mechanisms for the disorder. These include central sensitization, central disinhibition and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis. However, the central effects associated with FM can be produced by a peripheral source of pain. Chronic nociceptive input induces central sensitization, magnifying pain, and it activates the HPA and the sympathetic nervous system. Chronic sympathetic activation indirectly sensitizes peripheral nociceptors and sets up a vicious cycle. Thus, it appears that central mechanisms of FM pain are dependent on abnormal peripheral input(s) for development and maintenance of this condition. A substantial literature defines peripheral-CNS-peripheral interactions that are integral to FM pain. These reciprocal actions and related phenomena of relevance to FM pain are reviewed here, leading to suggestions for testing of therapeutic approaches.

Publication types

  • Review

MeSH terms

  • Chronic Disease
  • Fibromyalgia / complications
  • Fibromyalgia / physiopathology*
  • Fibromyalgia / therapy
  • Humans
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology*
  • Hyperalgesia / therapy
  • Nociceptors / physiology*
  • Pain / etiology
  • Pain / physiopathology*
  • Pain Management