The Role of Neurogenic Inflammation in Fibromyalgia Pathophysiology

Neurogenic inflammation refers to the inflammation that is the result of the release of various neuropeptides, chemokines, and cytokines from the peripheral endings of sensory nerves in response to tissue damage or painful stimuli. In the setting of wound healing, neurogenic inflammation helps maintain tissue integrity and facilitate tissue repair.1 However, neurogenic inflammation has also been implicated in the pathophysiology of numerous diseases, including complex regional pain syndrome, migraine, and irritable bowel and bladder syndromes.

A 2018 review in Seminars in Immunopathology by Geoffrey Littlejohn, MD, of Monash University, Melbourne, Australia, presents evidence that many of the characteristic symptoms of fibromyalgia result from neurogenic inflammation in both the central nervous system and periphery.2 Common clinical features of fibromyalgia that may be influenced by neurogenic inflammation include cutaneous manifestations, local soft tissue swelling and fluid retention, reticular skin discoloration and livedo reticularis, and increased levels of fibronectin, which is a tissue marker of endothelial activation.

Rheumatology Advisor interviewed Dr Littlejohn for additional clinical perspective on the pathophysiology of fibromyalgia and the role of neurogenic inflammation in the disease process.

Rheumatology Advisor: Why has it been so difficult for researchers to determine the pathophysiologic mechanisms of fibromyalgia?

Dr Littlejohn: The key clinical features of fibromyalgia that researchers first focused on were widespread pain and abnormal tenderness to gentle pressure. This was originally thought to predominantly involve muscles, so initial research focused on a peripheral muscular origin of the pain and soft-tissue sensitivity. It was later evident that all peripheral tissues, not just muscles, have lowered pain thresholds in fibromyalgia, indicating that a central neurophysiologic abnormality in the pain-related neural systems is the cause for the altered sensitivity. This is linked to the increased sensitivity seen in other sensory systems in fibromyalgia, including increased sensitivity to noise, light, balance, and various chemicals. Thus, as time went on, the focus shifted to identifying abnormal mechanisms in the higher centers involved with pain and other sensory modulation, particularly those in the spinal cord and brain. All of this took time and required better investigative tools, including imaging techniques like functional MRI and sampling of neuroactive biologic factors in peripheral and spinal fluids.


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