Role of Etanercept and Infliximab on Nociceptive Changes Induced by the Experimental Model of Fibromyalgia

Abstract

Background: Fibromyalgia is a clinical condition that affects 1% to 5% of the population. No proper therapy has been currently found. It has been described that inflammation plays a central role in the nerve sensitizations that characterize the pathology. Methods: This paper aimed to evaluate the efficacy of etanercept and infliximab in the management of pain sensitization. Fibromyalgia was induced by three injections once a day of reserpine at the dose of 1 mg/kg. Etanercept (3 mg/kg) and infliximab (10 mg/kg) were administered the day after the last reserpine injection and then 5 days after that. Behavioral analyses were conducted once a week, and molecular investigations were performed at the end of the experiment. Results: Our data confirmed the major effect of infliximab administration as compared to etanercept: infliximab administration strongly reduced pain sensitization in thermal hyperalgesia and mechanical allodynia. From the molecular point of view, infliximab reduced the activation of microglia and astrocytes and the expression of the purinergic P2X7 receptor ubiquitously expressed on glia and neurons. Downstream of the P2X7 receptor, infliximab also reduced p38-MAPK overexpression induced by the reserpine administration. Conclusion: Etanercept and infliximab treatment caused a significant reduction in pain. In particular, rats that received infliximab showed less pain sensitization. Moreover, infliximab reduced the activation of microglia and astrocytes, reducing the expression of the purinergic receptor P2X7 and p38-MAPK pathway.

Açai Berry Mitigates Vascular Dementia-Induced Neuropathological Alterations Modulating Nrf-2/Beclin1 Pathways

“…Extracts from cytosol and nucleus were prepared as previously described and incubated with the antibodies anti-NRF-2 (1–500, SCB, Heidelberg, Germany, #sc-365949), anti-heme oxygenase 1 (HO-1; 1-500, SCB, Heidelberg, Germany, #sc-136960), anti-β-tubulin (1–500, SCB, Heidelberg, Germany, #sc-166729), and anti-MAP2 (1–500, SCB, Heidelberg, Germany, #sc-74421) in 1× PBS, 5% w / v non-fat dried milk and 0.1% Tween-20 at 4 °C overnight [ 46 , 47 , 48 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ]. For the cytosolic and nuclear fraction, blots were also probed with β-actin and lamin A/C protein to ensure that they were filled with equivalent amounts of proteins (1:500; Santa Cruz Biotechnology).…”

Chronic Exposure to Vinclozolin Induced Fibrosis, Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis in Mice Kidney

“…Cytosolic and nuclear extracts were prepared as follows [ 72 ]: kidney tissues from mice were suspended in extraction Buffer A containing 0.2 mM PMSF, 0.15 mM pepstatin A, 20 mM leupeptin, and 1 mM sodium orthovanadate, homogenized at the highest setting for 2 min, and centrifuged at 12,000 rpm for 4 min at 4 °C. Supernatants represented the cytosolic fraction.…”

Chronic Exposure to Endocrine Disruptor Vinclozolin Leads to Lung Damage via Nrf2–Nf-kb Pathway Alterations

“…SOD activity assay was performed following the method described by Marklund and Marklund at 420 nm [ 9 , 10 , 55 , 56 ]. The results are presented as SOD units/mg protein.…”