A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia.

This narrative review summarizes the current knowledge of the genetic and epigenetic contributions to the development of fibromyalgia (FM). Although there is no single gene that results in the development of FM, this study reveals that certain polymorphisms in genes involved in the catecholaminergic pathway, the serotonergic pathway, pain processing, oxidative stress, and inflammation may influence susceptibility to FM and the severity of its symptoms. Furthermore, epigenetic changes at the DNA level may lead to the development of FM. Likewise, microRNAs may impact the expression of certain proteins that lead to the worsening of FM-associated symptoms.

A 60-Year-Old Man with a 34-Year History of Chronic Exertional Compartment Syndrome and 3 Previous Surgical Fasciotomies, Successfully Treated with Injection of Botulinum Toxin.

BACKGROUND Patients with post-fasciotomy CECS recurrence can experience significant mobility issues at baseline that limit independent living. For these patients, a repeat fasciotomy is not ideal because they are older and post-surgical scar tissue will make the fasciotomy technically challenging. Therefore, post-fasciotomy patients with CECS recurrence require new, non-surgical treatment options. Recent studies show botulinum toxin injections can be effective for the initial management of chronic exertional compartment syndrome (CECS) prior to surgery, especially in young patients primarily experiencing pain on exertion with minimal lower-extremity symptoms at rest. However, the ability to treat CECS recurrence status after fasciotomy with botulinum toxin injections of the legs has not been studied. CASE REPORT We present the first case where botulinum toxin was applied to this patient population. Our patient was a 60-year-old man with a 34-year history of CECS who, 8 years after his third bilateral fasciotomy, progressively developed rest pain in his calves bilaterally, paresthesias, and difficulties when walking or descending stairs, with multiple near-falls due to his toes catching on stair steps. OnabotulinumtoxinA (BTX-A) injections into the posterior and lateral compartments resolved baseline symptoms: within 2 weeks, he was able to walk, negotiate stairs symptom-free, and enjoy an overseas vacation without complications. CONCLUSIONS Symptoms related to recurrent CECS status after multiple fasciotomies can successfully be treated with BTX-A injections. Our patient's baseline mobility issues resolved within 2 weeks after the injection and remained that way for over 31 months. However, his exertional symptoms and rest pain recurred at 9 months, suggesting that BTX-A injections are not completely curative.

Modulation of Poly ADP Ribose Polymerase (PARP) Levels and Activity by Alcohol Binge-Like Drinking in Male Mice.

Binge drinking is a frequent pattern of ethanol consumption within Alcohol Use Disorders (AUDs). Binge-like ethanol exposure increases Poly(ADP-ribose) polymerase (PARP) expression and activity. PARP enzymes have been implicated in addiction and serve multiple roles in the cell, including gene expression regulation. In this study, we examined the effects of binge-like alcohol consumption in the prefrontal cortex (PFC) of adult C57BL/6J male mice via a 4-day Drinking-in-the-Dark (DID) paradigm. The role of PARP in associated gene expression and behavioral changes was assessed by administering the PARP inhibitor ABT-888 on the last DID day. We then conducted an RNA-seq analysis of the PFC gene expression changes associated with DID-consumed ethanol or ABT-888 treatment. A separate cohort of mice was inoculated with an HSV-PARP1 vector in the PFC and subject to a DID experiment to verify whether overexpressed PARP1 increased ethanol drinking. We confirmed that alcohol increases Parp1 gene expression and PARP activity in the PFC. RNA-seq showed significantly altered expression of 41 genes by DID-consumed ethanol, and of 48 genes by ABT-888. These results were confirmed by qPCR in 7 of the 10 genes validated, 4 of which have been previously associated with addiction. ABT-888 reduced, and overexpression of PFC PARP1 increased DID ethanol consumption. In our model, alcohol binge drinking induced specific alterations in the PFC expression of genes potentially involved in addiction. Pharmacological PARP inhibition proved effective in reversing these changes and preventing further alcohol consumption. Our results suggest an involvement of ethanol-induced PARP1 in reinforcing binge-like addictive behavior.