Modafinil Reduces Neuronal Pyroptosis and Cognitive Decline After Sleep Deprivation
Sleep deprivation (SD) induces systemic inflammation that promotes neuronal pyroptosis. The purpose of this study was to investigate the effect of an antioxidant modafinil on neuronal pyroptosis and cognitive decline following SD. Using a mouse model ...
reduced proinflammatory factor (IL-1β, TNF-α, and IL-6) production, and increased the expression of anti-inflammatory factors (IL-10).
This probably speaks to its role in combating pain in FMS.
Modafinil treatment attenuated inflammasome activity and reduced neuronal pyroptosis involving the NLRP3/NLRP1/NLRC4-caspase-1-IL-1β pathway
Impact of mast cells in fibromyalgia and low-grade chronic inflammation: Can IL-37 play a role? - PubMed
Fibromyalgia (FM) is a disease characterized by chronic widespread pain, fatigue, aches, joint stiffness, depression, cognitive dysfunction, and nonrestorative sleep. In FM, neurotransmission and glial activation can occur with an increase in inflammatory cytokines and involvement of mast cells (MCs …
T helper 1 response is correlated with widespread pain, fatigue, sleeping disorders and the quality of life in patients with fibromyalgia and is modulated by hyperbaric oxygen therapy - PubMed
FM patients show a Th1 signature and the activation of this subset is modulated by HBOT.
Objectives: Hyperbaric oxygen therapy (HBOT) has been used as treatment for different clinical conditions, including fibromyalgia (FM). HBOT modulates brain activity, ameliorates chronic pain and modifies the ratio of immune cells. Clinical studies have provided evidence that FM is associated with immune system dysregulation.
Results: Our results confirm the participation of immune system in the pathogenesis of FM and highlight the impact of HBOT treatment, with particular regard to the changes on proinflammatory cytokines production by CD4 T cells subsets.
Conclusions: FM patients show a Th1 signature and the activation of this subset is modulated by HBOT.
T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives
Fibromyalgia is one of the most important “rheumatic” disorders, after osteoarthritis. The etiology of the disease is still not clear. At the moment, the most defined pathological mechanism is the alteration of central pain pathways, and ...
The Vast Majority of Patients With Fibromyalgia Have a Straight Neck Observed on a Lateral View Radiograph of the Cervical Spine: An Aid in the Diagnosis of Fibromyalgia and a Possible Clue to the Etiology
My mom with FMS and I do have a straight neck. Mine actually curves the other way too much. It has the beginnings of arthritis in it.
Altered amino acid homeostasis in subjects affected by fibromyalgia | Request PDF
Request PDF | Altered amino acid homeostasis in subjects affected by fibromyalgia | To evaluate plasma amino acid (AA) concentrations in patients affected by fibromyalgia (FM) and to study the relationships between their levels... | Find, read and cite all the research you need on ResearchGate
Significant lower plasma taurine, alanine, tyrosine (Tyr), valine, methionine, phenylalanine and threonine concentrations, and the sum of essential AAs were observed in FM patients vs healthy controls (P<0.05). Tyr CAA' ratio and the sum of AAs competing with tryptophan for brain uptake were significantly reduced in FM (P<0.05). A significant correlation was found between FM clinical parameters and certain AAs.
Our results suggest probable defects of gut malabsorption of certain AAs in FM patients.
Significant lower plasma taurine, alanine, tyrosine (Tyr), valine, methionine, phenylalanine and threonine concentrations, and the sum of essential AAs were observed in FM patients vs healthy controls (P<0.05). Tyr CAA' ratio and the sum of AAs competing with tryptophan for brain uptake were significantly reduced in FM (P<0.05). A significant correlation was found between FM clinical parameters and certain AAs. Our results suggest probable defects of gut malabsorption of certain AAs in FM patients.
Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma
In addition to central hyperexcitability and impaired top–down modulation, chronic inflammation probably plays a role in the pathophysiology of fibromyalgia (FM). Indeed, on the basis of both animal experiments and human studies involving the ...
Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma
Patients with Fibromyalgia and Chronic Fatigue Syndrome show increased hsCRP compared to healthy controls
Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are both chronic disorders that have a devastating effect on the lives of the affected patients a…
Patients with Fibromyalgia and Chronic Fatigue Syndrome show increased hsCRP compared to healthy controls
Fibromyalgia (FM) is a disorder characterized by chronic diffuse pain and enhanced pain response to stimuli and is caused by central sensitization Tinnitus also is related to central sensitization So we investigated the impact of tinnitus on FMWe included ...
The FM patients with severe tinnitus had more functional impairments and lower quality of life than those with mild tinnitus Severe insomnia also was accompanied by worse health status and lower quality of life
Mitochondrial Enhancers for ME/CFS and Fibromyalgia Pt IV: N-Acetyl Cysteine (NAC) - Health Rising
This is bookmarked because FMS symptoms like mitochondrial dysfunction and ischemia overlap with those of ME/CFS. Interesting choice of supplement suggestions backed with research.
N-acetyl cysteine or NAC is a most interesting compound. Most often thought of as an antioxidant it appears to be able to enhance mitochondrial production as well.
Perhaps the most powerful antioxidant available and certainly the most widely studied, NAC is able to rejuvenate the levels of glutathione – the most powerful antioxidant in the body. It appears to do its work mostly in the mitochondria where recent research indicates it also triggers the production of hydrogen sulfide which, in turn, produces antioxidant effects and perhaps enhances ATP production as well.
A 2019 hypothesis paper proposed that supplements like coenzyme Q10, melatonin, curcumin, molecular hydrogen, and N-acetylcysteine could be helpful in ME/CFS patients with inflammation, increased oxidative and nitrosative stress, leaky gut, and mitochondrial dysfunction.
Shungu, interestingly, does not believe ME/CFS is a mitochondrial disorder. The mitochondria are affected in ME/CFS but at its heart, Shungu believes ME/CFS is an oxidative stress-induced micro-circulatory disease. High levels of oxidative stress are causing the blood vessels to shut down, making it impossible for the oxygen the mitochondria need to get through. Shungu’s hypothesis, which was produced some time ago, is circling around the same blood flow issues that other hypotheses are.
Luteolin: A promising natural agent in management of pain in chronic conditions
Pain due to chronic conditions is a frequent and insufficiently addressed problem. Current drug options for pain management (either in cases of chronic inflammatory conditions or neuropathy) do not adequately treat pain. Moreover, they are associated ...
The data reviewed strongly support luteolin's promising benefits in pain management and raise the need for further clinical trials that can establish its role in clinical practice.
Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C - PubMed
Pregabalin = An immunomodulator, then? Substance P stimulates immune cells to release things.
Our results suggest that gabapentin and pregabalin modulate the release of sensory neuropeptides, but only under conditions corresponding to significant inflammation-induced sensitization of the spinal cord.
It’s worth hearing him out; he cites studies, and he is not the only one with this theory. SIBO and fibromyalgia are strongly correlated, and as he shows, it is more likely that SIBO could cause [some cases of] fibromyalgia and not the other way around.
Accelerated Brain Gray Matter Loss in Fibromyalgia Patients: Premature Aging of the Brain?
Fibromyalgia is an intractable widespread pain disorder that is most frequently diagnosed in women. It has traditionally been classified as either a musculoskeletal disease or a psychological disorder. Accumulating evidence now suggests that fibromyalgia may be associated with CNS dysfunction. In this study, we investigate anatomical changes in the brain associated with fibromyalgia. Using voxel-based morphometric analysis of magnetic resonance brain images, we examined the brains of 10 female fibromyalgia patients and 10 healthy controls. We found that fibromyalgia patients had significantly less total gray matter volume and showed a 3.3 times greater age-associated decrease in gray matter than healthy controls. The longer the individuals had had fibromyalgia, the greater the gray matter loss, with each year of fibromyalgia being equivalent to 9.5 times the loss in normal aging. In addition, fibromyalgia patients demonstrated significantly less gray matter density than healthy controls in several brain regions, including the cingulate, insular and medial frontal cortices, and parahippocampal gyri. The neuroanatomical changes that we see in fibromyalgia patients contribute additional evidence of CNS involvement in fibromyalgia. In particular, fibromyalgia appears to be associated with an acceleration of age-related changes in the very substance of the brain. Moreover, the regions in which we demonstrate objective changes may be functionally linked to core features of the disorder including affective disturbances and chronic widespread pain.
Fibromyalgia is characterized by altered frontal and cerebellar structural covariance brain networks - PubMed
Altered brain morphometry has been widely acknowledged in chronic pain, and recent studies have implicated altered network dynamics, as opposed to properties of individual brain regions, in supporting persistent pain. Structural covariance analysis determines the inter-regional association in morpho …
spectral partitioning identified a distinct submodule with cerebellar connections to medial prefrontal and temporal and right inferior parietal lobes, whose gray matter volume was associated with the severity of depression in these patients.
Fibromyalgia impact in the prefrontal cortex subfields: An assessment with MRI
Women with fibromyalgia showed reduced volume in different subfields of the prefrontal cortex and total gray matter compared to healthy women.
•
Various subfields of the prefrontal cortex showed significantly volumetric decreases related to variables such as age and depression.
•
The total gray matter shows a significant decrease related to age observed through the analysis of multiple linear regressions.
Women with fibromyalgia showed reduced volume in different subfields of the prefrontal cortex and total gray matter compared to healthy women.•Various subfields of the prefrontal cortex showed significantly volumetric decreases related to variables such as age and depression.•The total gray matter shows a significant decrease related to age observed through the analysis of multiple linear regressions.
The Link between Fibromyalgia Syndrome and Anger: A Systematic Review Revealing Research Gaps
Anger has been associated with increased pain perception, but its specific connection with Fibromyalgia Syndrome (FMS) has not yet been established in an integrated approach. Therefore, the present systematic review focuses on exploring this connection, ...
Effect of Steroids on Patients With Fibromyalgia/Chromic Widespread Pain: An Observational Study
Objective: Fibromyalgia causes widespread chronic pain. Pain management and treating underlying conditions are of utmost importance. Recent studies found an association of thyroid autoimmunity with fibromyalgia. Pain management of patients with anti-thyroid ...
We found that 51.6% of the patients responded well to the steroid therapy
Anti-satellite glia cell IgG antibodies in fibromyalgia patients are related to symptom severity and to metabolite concentrations in thalamus and rostral anterior cingulate cortex
Recent translational work has shown that fibromyalgia might be an autoimmune condition with pathogenic mechanisms mediated by a peripheral, pain-induc…
Repeated cold stress, an animal model for fibromyalgia, elicits proprioceptor-induced chronic pain with microglial activation in mice - Journal of Neuroinflammation
Background Fibromyalgia is characterized by chronic pain, fatigue, and other somatic symptoms. We have recently revealed that proprioceptor hyperactivation induces chronic pain in a rat model of myalgic encephalomyelitis. The present study explores whether similar proprioceptor-induced pain is elicited in a mouse model of fibromyalgia. Methods Repeated cold stress (RCS) was used as a fibromyalgia model. Pain behavior was examined using the von Frey test, and neuronal activation was examined immunohistochemically as activating transcription factor (ATF)3 expression. The Atf3:BAC transgenic mouse, in which mitochondria in hyperactivated neurons are specifically labeled by green fluorescent protein, was used to trace the activated neuronal circuit. PLX3397 (pexidartinib) was used for microglial suppression. Results RCS elicited long-lasting pain in mice. ATF3, a marker of cellular hyperactivity and injury, was expressed in the lumbar dorsal root ganglion (DRG) 2 days after RCS initiation; the majority of ATF3-expressing DRG neurons were tropomyosin receptor kinase C- and/or vesicular glutamate transporter 1-positive proprioceptors. Microglial activation and increased numbers of microglia were observed in the medial part of the nucleus proprius 5 days after RCS initiation, and in the dorsal region of the ventral horn 7 days after RCS. In the ventral horn, only a subset of motor neurons was positive for ATF3; these neurons were surrounded by activated microglia. A retrograde tracer study revealed that ATF3-positive motor neurons projected to the intrinsic muscles of the foot (IMF). Using Atf3:BAC transgenic mice, we traced hyperactivated neuronal circuits along the reflex arc. Green fluorescent protein labeling was observed in proprioceptive DRG neurons and their processes originating from the IMF, as well as in motor neurons projecting to the IMF. Microglial activation was observed along this reflex arc, and PLX3397-induced microglial ablation significantly suppressed pain behavior. Conclusion Proprioceptor hyperactivation leads to local microglial activation along the reflex arc; this prolonged microglial activation may be responsible for chronic pain in the present model. Proprioceptor-induced microglial activation might be the common cause of chronic pain in both the fibromyalgia and myalgic encephalomyelitis models, although the experimental models are different.
Neutrophils infiltrate sensory ganglia and mediate chronic widespread pain in fibromyalgia | PNAS
Conclusion: “We used a model of hyperalgesic priming to induce chronic widespread pain in mice that resulted in robust and persistent ipsilateral and contralateral behavioral hypersensitivity and sensitization of spinal cord neurons. Adoptive transfer of neutrophils from primed mice and from patients with fibromyalgia syndrome confers mechanical pain to recipient naïve mice, sensitizes evoked action potential firing of spinal cord neurons, and causes neutrophil infiltration into the dorsal root ganglia. These data demonstrate that neutrophils are fundamental for the development of chronic widespread pain through infiltration of peripheral sensory ganglia. Further studies characterizing the neutrophil phenotype in fibromyalgia syndrome may shed light on mediators of the cross talk between these polymorphonuclear granulocytes and sensory neurons. Our findings suggest that targeting neutrophils may be useful therapeutic targets for pain control in fibromyalgia.”
Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia
Conclusion: “This study identified a neuro-immune interface between peripheral nerves and NK cells in FMS patients that suggests a novel mechanism for FMS pathogenesis and a new direction in the development of therapeutic options to treat this poorly managed syndrome.”
