Inflammatory Biochemical Mediators and Their Role in Myofascial Pain and Osteopathic Manipulative Treatment: A Literature Review.

Chronic inflammatory pain conditions, specifically myofascial pain (MFP), account for an overwhelming percentage of office visits every day. The combination of the high cost of its treatment and frequent patient visits makes MFP a critical pathology to be investigated. Sharpening our understanding of the molecular mechanisms within MFP will expedite the enhancement of therapeutic approaches. Inflammation plays a critical role in the pathophysiology of MFP. The chief inflammatory mediators of interest in this review related to MFP are interleukin 1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α). This review aimed to determine the impact of inflammatory mediators on fibroblasts and satellite cells, specifically their role in muscle injury and regeneration. Blocking pro-inflammatory mediators such as IL-1ß, IL-6, and TNF-α in these cell types could prove to be an effective treatment for MFP. An osteopathic manipulative treatment (OMT) modality, specifically indirect counterstrain therapy, was investigated in the hopes of elucidating a reduction in particular cytokines. In addition, myofascial release (MFR) therapies (OMT modality) were explored as a potentially effective treatment through the acceleration of wound healing, stimulation of muscle regeneration, and decreased inflammation via altered fibroblast activity. Pharmacologic agents such as non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat MFP but have a higher adverse side effect profile compared to OMT therapy. The optimal management of MFP is likely multifactorial, and more treatment modalities must be explored. This literature review analyzed 17 peer-reviewed articles specifically related to MFP management and the role of inflammation in MFP. Chronic inflammation from other etiologies was excluded. Our aim was to elucidate the biochemical mechanisms underlying MFP and inflammation in an effort to promote the medical community's understanding of treatment modalities for this chronic condition. This study revealed that various OMT techniques such as MFR and counterstrain lead to changes on the cellular level in MFP. Discovering similar effects on biochemical inflammatory markers with non-pharmacologic treatment modalities was an exciting revelation and one that could potentially change the way physicians address pain management.

Genetic polymorphism analysis of patients with primary hyperhidrosis.

BACKGROUND: Hyperhidrosis affects 220 million people worldwide. The hallmark of this condition is excessive sweating, which negatively impacts the social, emotional, and occupational lives of these individuals. A familial predisposition has been established; however, the specific genes involved have yet to be identified. OBJECTIVE: The aim of this study was to determine possible genetic variations contributing to primary hyperhidrosis, specifically single-nucleotide polymorphisms (SNPs). PATIENTS AND METHODS: Twenty-one case and 21 control DNA samples were extracted and genotyped for 20 SNPs associated with the Butyrylcholinesterase (BCHE) and Cholinergic Receptor Nicotinic Alpha-7 subunit (CHRNA7) genes. RESULTS: For rs1126680, the -116A variant allele (P-value=0.15) was found only in hyperhidrosis patients who also had the K-variant allele (P-value=0.65) in rs1803274. Further analysis testing the null hypothesis of independence between the combined genotypes and case/control status yielded a P-value of 0.30. CONCLUSION: Our results are consistent with previous research that shows the K-variant requires the -116A variant to be present in order to observe a decrease in BChE activity levels. These results are not statistically significant (P-value >0.05), but the exclusive association between the -116A and K-variants on the BCHE gene in hyperhidrosis patients warrants further investigation using a larger sample size.

Isocitrate ameliorates anemia by suppressing the erythroid iron restriction response.

The unique sensitivity of early red cell progenitors to iron deprivation, known as the erythroid iron restriction response, serves as a basis for human anemias globally. This response impairs erythropoietin-driven erythropoiesis and underlies erythropoietic repression in iron deficiency anemia. Mechanistically, the erythroid iron restriction response results from inactivation of aconitase enzymes and can be suppressed by providing the aconitase product isocitrate. Recent studies have implicated the erythroid iron restriction response in anemia of chronic disease and inflammation (ACDI), offering new therapeutic avenues for a major clinical problem; however, inflammatory signals may also directly repress erythropoiesis in ACDI. Here, we show that suppression of the erythroid iron restriction response by isocitrate administration corrected anemia and erythropoietic defects in rats with ACDI. In vitro studies demonstrated that erythroid repression by inflammatory signaling is potently modulated by the erythroid iron restriction response in a kinase-dependent pathway involving induction of the erythroid-inhibitory transcription factor PU.1. These results reveal the integration of iron and inflammatory inputs in a therapeutically tractable erythropoietic regulatory circuit.