Abstract

Fibromyalgia is a debilitating widespread chronic pain syndrome that occurs in 2-4% of the population. The prevailing view that fibromyalgia results from central nervous system dysfunction has recently been challenged with data showing changes in peripheral nervous system activity. Using a mouse model of chronic widespread pain through hyperalgesic priming of muscle, we show that neutrophils invade sensory ganglia and confer mechanical hypersensitivity on recipient mice, whilst adoptive transfer of immunoglobulin, serum, lymphocytes or monocytes have no effect on pain behaviour. Neutrophil depletion abolishes the establishment of chronic widespread pain in mice. Neutrophils from patients with fibromyalgia also confer pain on mice. A link between neutrophil derived mediators and peripheral nerve sensitisation is already established. These observations suggest new approaches for targeting fibromyalgia pain through an understanding of the mechanisms that cause altered neutrophil activity and interactions with sensory neurons. Significance statementWe used a back-translational model in mice to demonstrate the pro-nociceptive role of neutrophils in fibromyalgia. Adoptive transfer of neutrophils from mice with chronic widespread pain or from patients with fibromyalgia can confer mechanical pain to recipient naive mice, sensitise evoked action potential firing of spinal cord neurons and produce phenotypic changes in cell surface expression of neutrophil proteins that cause infiltration of neutrophils into dorsal root ganglia. These data provide the framework for an immunological basis of chronic widespread pain in fibromyalgia mediated by polymorphonuclear granulocytes.