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Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome

Key Points

  • Fibromyalgia and complex regional pain syndrome (CRPS) have distinct clinical phenotypes but share features such as pain, allodynia and peripheral dysaesthesia

  • Factors involving the brain and spinal cord lead to central sensitization, which has a dominant role in both disorders

  • Neurogenic inflammation, resulting from the release of proinflammatory neuropeptides from C-fibres, is also prominent in both disorders and contributes to allodynia, tissue swelling and dysaesthesia

  • Neurogenic inflammation involves interactions of the innate immune system with the peripheral and central nervous systems of patients with fibromyalgia or CRPS

  • Although the pathogenesis of both fibromyalgia and CRPS is dominated by central mechanisms, components of neurogenic neuroinflammation might be useful therapeutic targets in patients with these disorders


Although fibromyalgia and complex regional pain syndrome (CRPS) have distinct clinical phenotypes, they do share many other features. Pain, allodynia and dysaesthesia occur in each condition and seem to exist on a similar spectrum. Fibromyalgia and CRPS can both be triggered by specific traumatic events, although fibromyalgia is most commonly associated with psychological trauma and CRPS is most often associated with physical trauma, which is frequently deemed routine or minor by the patient. Fibromyalgia and CRPS also seem to share many pathophysiological mechanisms, among which the most important are those involving central effects. Nonetheless, peripheral effects, such as neurogenic neuroinflammation, are also important contributors to the clinical features of each of these disorders. This Review highlights the differing degrees to which neurogenic neuroinflammation might contribute to the multifactorial pathogenesis of both fibromyalgia and CRPS, and discusses the evidence suggesting that this mechanism is an important link between the two disorders, and could offer novel therapeutic targets.

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Figure 1: Central and peripheral effects associated with release of neuropeptides by terminal C-fibres.
Figure 2: Clinical features of neurogenic inflammation in fibromyalgia and complex regional pain syndrome.


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Littlejohn, G. Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome. Nat Rev Rheumatol 11, 639–648 (2015).

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