Analysis of the Influence of IL-6 and the Activation of the Jak/Stat3 Pathway in Fibromyalgia

Abstract

Background: Fibromyalgia is a medical condition that affects a small percentage of the population, with no known effective treatment. There is evidence to suggest that inflammation is a key factor in the nerve sensitization that characterizes the disorder. Therefore, this paper concentrates on the role of IL-6 in fibromyalgia and the related pain-like symptoms. Methods: This work aimed to evaluate Sprague–Dawley rats, which were injected for three consecutive days with 1 mg/kg of reserpine; IL-6-R Ab was intraperitoneally injected at 1.5 mg/kg seven days after the first reserpine injection. Behavioral analyses were conducted at the beginning of the experiment and at seven and twenty-one days from the first reserpine injection. At this timepoint, the animals were sacrificed, and tissues were collected for molecular and histological analysis. Results: Our data showed the analgesic effect of IL-6-R-Ab administration on mechanical allodynia and thermal hyperalgesia. Additionally, the reserpine + IL-6-R-Ab group showed a reduced expression of the pain-related mediators cFOS and NFG and reduced levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and chemokines (Cxcl5, Cxcl10 and Cx3cl1). From the molecular point of view, the IL-6-R-Ab administration reduced the gp130 phosphorylation and the activation of the Jak/STAT3 pathway. Additionally, the IL-6-R Ab reduced the activation of neuroinflammatory cells. Conclusions: Our study showed that IL-6 plays a crucial role in fibromyalgia by triggering the Jak/STAT3 pathway, leading to an increase in chemokine levels and activating glial cells.

Effects of buccal acupuncture on postoperative analgesia in elderly patients undergoing laparoscopic radical gastrectomy: a randomized controlled trial

“…Surgical trauma aggravated postoperative pain and inflammatory response by releasing inflammatory mediators, which could be alleviated by an effective preoperative regional anesthesia to inhibit the transmission of trauma and pain stimulation to the advanced center ( 14 , 27 ). IL-6 is the earliest released and highly sensitive proinflammatory factor, closely related to the severity of surgical trauma, body immune status and prognosis ( 28 ). IL-10, as an inflammatory suppressor, inhibits nuclear factor activity and promotes neutrophil apoptosis ( 29 ).…”

The interplay between M1/M2 macrophages and sensory neurons in pain modulation

“…Macrophages use various mechanisms to induce pain. Typically, M1 macrophages release a multitude of inflammatory mediators, including interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) (15,16), interleukin-6 (IL-6) (17,18), nerve growth factor (NGF) (19), insulin-like growth factor 1 (IGF-1) (20), COX2 and PGE2 (21), which stimulate their specific receptors expressed in the nociceptive neurons. This activation leads to the generation of various neuronal cell signals, such as Ca2+ and cAMP, PKA, PKC, PI3K, MAPKs (ERK, p38, and JNK), NF-κB, JAK, STAT, and Src.…”