Peripheral pain mechanisms in chronic widespread pain

Abstract

Clinical symptoms of chronic widespread pain (CWP) conditions like fibromyalgia (FM), include pain, stiffness, subjective weakness, and muscle fatigue. Muscle pain in CWP is usually described as fluctuating and often associated with local or generalised tenderness (hyperalgesia and/or allodynia). This tenderness related to muscle pain depends on increased peripheral and/or central nervous system responsiveness to peripheral stimuli, which can be either noxious (hyperalgesia) or non-noxious (allodynia). For example, patients with muscle hyperalgesia will rate painful muscle stimuli higher than normal controls, whereas patients with allodynia may perceive light touch as painful, something that a 'normal' individual will never describe as painful. The pathogenesis of such peripheral and/or central nervous system changes in CWP is unclear, but peripheral soft tissue changes have been implicated. Indirect evidence from interventions that attenuate tonic peripheral nociceptive impulses in patients with CWP syndromes like FM suggest that overall FM pain is dependent on peripheral input. More importantly, allodynia and hyperalgesia can be improved or abolished by removal of peripheral impulse input. Another potential mechanism for CWP pain is central disinhibition. However, this pain mechanism also depends on tonic impulse input, even if only inadequately inhibited. Thus, a promising approach to understanding CWP is to determine whether abnormal activity of receptors in deep tissues is fundamental to the development and maintenance of this chronic pain disorder.

Conclusions: Most CWP patients present with focal tissue abnormalities including myofascial trigger points, ligamentous trigger points or osteoarthritis of the joints and spine. While not predictive for the development of CWP, these changes nevertheless represent important pain generators that may initiate or perpetuate chronic pain. Local chemical mediators, including lactic acid, adenosine triphosphate (ATP) and cytokines, seem to play an important role in sensitising deep tissue nociceptors of CWP patients. Thus, the combination of peripheral impulse input and increased central pain sensitivity may be responsible for widespread chronic pain disorders including FM.