Stem cells therapeutic effect in a reserpine-induced fibromyalgia rat model: A possible NLRP3 inflammasome modulation with neurogenesis promotion in the cerebral cortex

Mokhemer, Sahar Ahmed; Desouky, Maha K.; Abdelghany, Asmaa K.; Ibrahim, Manar Fouli Gaber

doi:10.1016/j.lfs.2023.121784

Cited by 8 publications

(2 citation statements)

References 79 publications

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“…Furthermore, treatment with SURM restored catecholamine levels in the thalamus of rats. This restoration may be linked to NLRP3 inhibition, as observed in studies where stem cell treatment restored brain monoamines in FM models (Mokhemer et al, 2023).…”

Section: Discussionmentioning

confidence: 84%

Thalamic Purinergic Receptors: A Gateway to Modulating Fibromyalgia Pain via NLRP3 Inflammasome Signaling and Pyroptosis

Kamel,

Mohamed,

Zaki

2024

Preprint

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The high pain sensitivity in fibromyalgia (FM) is processed by the thalamus that presents as a key component in the pain pathway in FM patients. Noteworthy, Purinergic receptors, specifically P2X, are implicated in pain signaling and neuroinflammation via inflammasome signaling. However, there is no available data on the impact of pharmacological intervention on P2X receptor in thalamic pain transmission in FM. To investigate this aspect, the clinically tested P2X inhibitor, Suramin (SURM), was utilized. FM was induced over three days using Reserpine (1 mg/kg/day, s.c.), followed by a single dose of SURM (100 mg/kg, i.p.). At the molecular level, SURM countered the overexpression of P2X7 and P2X4 receptors accompanied by reduced NLRP3 inflammasome complex and pyroptotic markers like gasdermin-D. This was associated by the suppression of the p38-MAPK and NF-κB pathways, along with a decrease in pro-inflammatory cytokines and tumor necrosis factor-α as observed by increased CD86 expression on M1 microglia phenotype, a neuroinflammatory marker. Concurrently, blocking the P2X receptor shifted microglia polarization towards the M2 phenotype, marked by elevated CD163 expression, as a neuroprotective mechanism. This was outlined by increased neurotrophic and anti-inflammatory; IL-10 with normalization of disturbed neurotransmitters. Behaviorally, SURM ameliorated the heightened pain processing, as observed in mechanical and thermal pain tests. Furthermore, it lowered Reserpine-induced motor impairment in the rotarod and open-field tests. This improvement in the somatosensory experience was reflected in alleviating depressive-like behavior in the forced swimming test. These findings highlight the therapeutic potential of blocking thalamic P2X receptors in alleviating fibromyalgia symptoms.

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Section: Discussionmentioning

confidence: 84%

Thalamic Purinergic Receptors: A Gateway to Modulating Fibromyalgia Pain via NLRP3 Inflammasome Signaling and Pyroptosis

Kamel,

Mohamed,

Zaki

2024

Preprint

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“…Proteolytic activation of IL-1 is controlled by inflammasomes, which are large multiprotein signaling platforms. This suggests that targeting the inflammasome could be a potential therapy for IL-1-mediated pain syndromes, including FM [ 33 , 34 ]. It has also been shown that IL-1 production is induced by mast cells following pathogenic infection, possibly associated with pain syndrome [ 35 , 36 ].…”

Section: The Innate Immune Systemmentioning

confidence: 99%

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

Paroli,

Gioia,

Accapezzato

et al. 2024

IJMS

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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.

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