Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome

  title={Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome},
  author={Geoffrey Owen Littlejohn},
  journal={Nature Reviews Rheumatology},
  • G. Littlejohn
  • Published 1 November 2015
  • Medicine, Psychology
  • Nature Reviews Rheumatology
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… 

Neurogenic inflammation in fibromyalgia

Emotional and stress-related physiological mechanisms are seen as upstream drivers of neurogenic inflammation in fibromyalgia, and may influence central symptoms, such as fatigue and changes in cognition.

Neuroinflammation in fibromyalgia and CRPS is multifactorial

In his Review article (Neurogenic neuro­ inflammation in fibromyalgia and com­ plex regional pain syndrome. Nat. Rev. Rheumatol. 11, 639–648; 2015)1, Geoffrey Littlejohn ascribes neuroinflammation to

Neuroinflammation in fibromyalgia and CRPS: top-down or bottom-up?

Research into the various observations surrounding neuroinflammation in fibromyalgia and CRPS is clearly needed, which should include establishment of the directionality of the different proposed mechanisms (top-down or bottom-up, or both), as well as more sophisticated clinical trials of proposed management strategies.

Comparison of complex regional pain syndrome and fibromyalgia

The present findings show that the CRPS and FM groups differ mainly in the high frequency, which may reflect their distinct pathophysiology and symptomatology.

Microstructural Evidence of Neuroinflammation for Psychological Symptoms and Pain in Patients With Fibromyalgia

This is the first study to use DKI to examine the brains of patients with fibromyalgia and noted significant DKI changes associated with neuroinflammation at specific areas in patients with FM.

Inflammation in the pathophysiology of neuropathic pain

The interplay of anti-inflammatory cytokines and the nociceptive system provides possibilities and challenges concerning treatment strategies based on this concept.

Fibromyalgia and its New Lessons for Neuropsychiatry

Better conceptualization of FM may also elucidate a neuropsychiatric understanding of how nociception, dysthymia, and suicidality co-develop and feed off one another.

Complex Regional Pain Syndrome: An update

This syndrome develops in two phases, the acute (warm) phase, with the classic symptoms of inflammation, and the chronic phase, often characterized by trophic changes of the soft tissues and even bones, which is the dominating feature.


Fibromyalgia is the common phenotype arising from the amalgamation of various aetiologies, and recruitment or amplification of the above 6 factors by various rheumatic diseases may thus lead precipitation of secondary FM in susceptible individuals.

Abnormal neuroinflammation in fibromyalgia and CRPS using [11C]-(R)-PK11195 PET.

This report is the first to describe abnormal neuroinflammation levels in the brains of FM patients compared with that in patients with CRPS using [11C]-(R)-PK11195 PET, and suggested that abnormal neuro inflammation can be an important pathological factor in FM.



Fibromyalgia and related conditions.

  • D. Clauw
  • Medicine
    Mayo Clinic proceedings
  • 2015

The science of fibromyalgia.

Evidence suggests that both the ascending and descending pain pathways operate abnormally, resulting in central amplification of pain signals, analogous to the "volume control setting" being turned up too high.

A Chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation

Results indicated that activated microglia were involved in the development of abnormal pain in CS animals, suggesting that the pain observed in CFS and FMS patients may be partly caused by a mechanism in which microglial activation is involved.

Central amplification and fibromyalgia: Disorder of pain processing

Two areas where strong evidence exists for abnormalities in sensory signaling: the reduction of descending control, including suppression of descending inhibitory pathways and/or enhancement of descending facilitatory pathways, and changes in key neurotransmitters associated with central sensitization are discussed.

Complex regional pain syndrome in adults.

Results from recent randomized controlled trials suggest that it is possible that some patients whose condition was considered refractory in the past can now be effectively treated, but confirmatory trials are required.

Status of immune mediators in complex regional pain syndrome type I

A review of recent study results shows a clear underlying inflammatory response at the local site of CRPS-I, where systemic responses seem to be inconsistent.