Neutrophils infiltrate sensory ganglia and mediate chronic widespread pain in fibromyalgia

Caxaria, Sara; Bharde, Sabah; Fuller, Alice M; Evans, Romy; Thomas, B.L.; Celik, Petek; Dell’Accio, Francesco; Yona, Simon; Gilroy, Derek W.; Voisin, Mathieu-Benoı̂t; Wood, John N.; Sikandar, Shafaq

doi:10.1073/pnas.2211631120

Cited by 23 publications

(11 citation statements)

References 71 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Supporting this conclusion, we found that (i) systemically administered clodronate and PLX5622 exert opposite effects on neutrophil numbers yet both treatments deplete monocytes and prevent priming; and (ii) local administration of clodronate depletes macrophages from the priming site but has no effect on HP induction. However, the results do not exclude the possibility that neutrophils, which promote widespread persistent nociception in a mouse model of fibromyalgia 81 , might play an ancillary role in HP, as also suggested by the modifications induced in this cell population by IL-6 treatment (present study). Second, our findings identify NAAA as a molecular switch that, when engaged, instructs monocytes to interact with first-order nociceptors and enable priming 19 – 21 .…”

Section: Discussioncontrasting

confidence: 74%

NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice

Fotio,

Mabou Tagne,

Squire

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Circulating monocytes participate in pain chronification but the molecular events that cause their deployment are unclear. Using a mouse model of hyperalgesic priming (HP), we show that monocytes enable progression to pain chronicity through a mechanism that requires transient activation of the hydrolase, N-acylethanolamine acid amidase (NAAA), and the consequent suppression of NAAA-regulated lipid signaling at peroxisome proliferator-activated receptor-α (PPAR-α). Inhibiting NAAA in the 72 hours following administration of a priming stimulus prevented HP. This effect was phenocopied by NAAA deletion and depended on PPAR-α recruitment. Mice lacking NAAA in CD11b+ cells – monocytes, macrophages, and neutrophils – were resistant to HP induction. Conversely, mice overexpressing NAAA or lacking PPAR-α in the same cells were constitutively primed. Depletion of monocytes, but not resident macrophages, generated mice that were refractory to HP. The results identify NAAA-regulated signaling in monocytes as a control node in the induction of HP and, potentially, the transition to pain chronicity.

show abstract

Section: Discussioncontrasting

confidence: 74%

NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice

Fotio,

Mabou Tagne,

Squire

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

“…In addition, neutrophil infiltration was found in the sensory ganglia of experimental mice. In the same study, neutrophils obtained from FM patients but not from controls and transferred into mice similarly induced diffuse pain syndrome [ 59 , 60 ]. All this evidence suggests that neutrophils may be a potential target in the treatment of FM.…”

Section: The Innate Immune Systemmentioning

confidence: 99%

Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review

Paroli,

Gioia,

Accapezzato

et al. 2024

IJMS

View full text Add to dashboard Cite

Fibromyalgia (FM) is a chronic disease characterized by widespread musculoskeletal pain of unknown etiology. The condition is commonly associated with other symptoms, including fatigue, sleep disturbances, cognitive impairment, and depression. For this reason, FM is also referred to as FM syndrome. The nature of the pain is defined as nociplastic according to the latest international classification and is characterized by altered nervous sensitization both centrally and peripherally. Psychosocial conditions have traditionally been considered critical in the genesis of FM. However, recent studies in animal models and humans have provided new evidence in favor of an inflammatory and/or autoimmune pathogenesis. In support of this hypothesis are epidemiological data of an increased female prevalence, similar to that of autoimmune diseases, and the frequent association with immune-mediated inflammatory disorders. In addition, the observation of an increased incidence of this condition during long COVID revived the hypothesis of an infectious pathogenesis. This narrative review will, therefore, discuss the evidence supporting the immune-mediated pathogenesis of FM in light of the most current data available in the literature.

show abstract

“…Indeed, the cxcl1 and cxcl2 gene were reported as the most rapidly expressed genes (1 h) at the site of incision in a recent unbiased cell sequencing study ( 168 ). Other studies indicate a role for neutrophils in chronic pain conditions, including fibromyalgia ( 169 ), although how they activate or sensitise nociceptors has not been resolved.…”

Section: Cellular Mechanisms Of Pppmentioning

confidence: 99%

The mechanisms and management of persistent postsurgical pain

2023

Self Cite

View full text Add to dashboard Cite

An estimated 10%–50% of patients undergoing a surgical intervention will develop persistent postsurgical pain (PPP) lasting more than 3 months despite adequate acute pain management and the availability of minimally invasive procedures. The link between early and late pain outcomes for surgical procedures remains unclear—some patients improve while others develop persistent pain. The elective nature of a surgical procedure offers a unique opportunity for prophylactic or early intervention to prevent the development of PPP and improve our understanding of its associated risk factors, such as pre-operative anxiety and the duration of severe acute postoperative pain. Current perioperative pain management strategies often include opioids, but long-term consumption can lead to tolerance, addiction, opioid-induced hyperalgesia, and death. Pre-clinical models provide the opportunity to dissect mechanisms underpinning the transition from acute to chronic, or persistent, postsurgical pain. This review highlights putative mechanisms of PPP, including sensitisation of peripheral sensory neurons, neuroplasticity in the central nervous system and nociceptive signalling along the neuro-immune axis.

show abstract

Neutrophils infiltrate sensory ganglia and mediate chronic widespread pain in fibromyalgia

Cited by 23 publications

References 71 publications

NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice

NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice

Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review

The mechanisms and management of persistent postsurgical pain

Contact Info

Product

Resources

About