New and emerging therapeutic agents for the treatment of fibromyalgia: an update

Fibromyalgia (FM) is a chronic widespread pain condition that is estimated to affect 5 million US adults. Several molecular pathophysiologies are thought to contribute to the symptoms of FM, complicating the development of effective clinical management techniques. It is now known that abnormalities in both nociceptive and central pain processing systems are necessary (but perhaps not sufficient) to condition the onset and maintenance of FM, producing associated neuropsychologic symptoms such as pronounced fatigue, sleep abnormalities, cognitive difficulties, stress sensitivity, anxiety, and depression. Current treatment strategies are focused primarily on correcting the pathophysiologic mechanisms underlying these nervous system abnormalities. Clinical studies demonstrate the safety and efficacy of three drugs recently approved for the treatment of FM: pregabalin (an alpha-2-delta ligand), and duloxetine and milnacipran (serotonin/norepinephrine reuptake inhibitors). This review describes these pharmaceuticals in detail and discusses their current roles in FM management

Recent Developments in the Management of Post- Traumatic Pain

A variety of analgesic options are currently available for the treatment of acute and chronic post-traumatic pain (PTP). These include nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and adjuvant analgesics (i.e., antidepressants, anticonvulsants, N-methyl-D-aspartate receptor antagonists), as well as muscle relaxants and local anesthetics. Unfavorable safety profiles have limited the use of many of these drugs in PTP management, however, and PTP often remains inadequately treated. Contemporary research has focused on the development of more efficacious pharmaceuticals with fewer associated side-effects, as well as on the use of non-pharmaceutical approaches, such as neurofeedback, to facilitate or enhance analgesia. This review discusses these advances in detail, providing an overview of the recent developments in the management of PTP

Deep Learning-based DSM Generation from Dual-Aspect SAR Data

Rapid mapping demands efficient methods for a fast extraction of information from satellite data while minimizing data requirements. This paper explores the potential of deep learning for the generation of high-resolution urban elevation data from Synthetic Aperture Radar (SAR) imagery. In order to mitigate occlusion effects caused by the side-looking nature of SAR remote sensing, two SAR images from opposing aspects are leveraged and processed in an end-to-end deep neural network. The presented approach is the first of its kind to implicitly handle the transition from the SAR-specific slant range geometry to a ground-based mapping geometry within the model architecture. Comparative experiments demonstrate the superiority of the dual-aspect fusion over single-image methods in terms of reconstruction quality and geolocation accuracy. Notably, the model exhibits robust performance across diverse acquisition modes and geometries, showcasing its generalizability and suitability for height mapping applications. The study’s findings underscore the potential of deep learning-driven SAR techniques in generating high-quality urban surface models efficiently and economically

The JAX Synteny Browser for mouse-human comparative genomics.

Visualizing regions of conserved synteny between two genomes is supported by numerous software applications. However, none of the current applications allow researchers to select genome features to display or highlight in blocks of synteny based on the annotated biological properties of the features (e.g., type, function, and/or phenotype association). To address this usability gap, we developed an interactive web-based conserved synteny browser, The Jackson Laboratory (JAX) Synteny Browser. The browser allows researchers to highlight or selectively display genome features in the reference and/or the comparison genome according to the biological attributes of the features. Although the current implementation for the browser is limited to the reference genomes for the laboratory mouse and human, the software platform is intentionally genome agnostic. The JAX Synteny Browser software can be deployed for any two genomes where genome coordinates for syntenic blocks are defined and for which biological attributes of the features in one or both genomes are available in widely used standard bioinformatics file formats. The JAX Synteny Browser is available at: http://syntenybrowser.jax.org/. The code base is available from GitHub: https://github.com/TheJacksonLaboratory/syntenybrowser and is distributed under the Creative Commons Attribution license (CC BY)

Advances in diagnostic and treatment options in patients with fibromyalgia syndrome

Jill M Recla1,21IGERT Program in Functional Genomics, Graduate School of Biomedical Sciences, The University of Maine, Orono, ME, USA; 2The Jackson Laboratory, Bar Harbor, ME, USADear Dr Liu,I have read with great interest the article entitled “Advances in diagnostic and treatment options in patients with fibromyalgia syndrome” by Gur and Oktayoglu, which has been published online in Open Access Rheumatology: Research and Reviews.1 The authors aimed to evaluate new diagnostic tools and new therapeutic treatment approaches for fibromyalgia (FM). I would like to comment on the article by referring to my recently published work in Medical Hypotheses,2 which the authors reference in their section on the N-methyl d-aspartate receptor (NMDAR) antagonist memantine. My article describes the hypothesis that a combined therapeutic approach of the pharmaceuticals pregabalin and memantine may provide analgesic and neuroprotective benefits to patients with FM. The authors’ statement, which directly references my work – “Memantine may also suppress neuronal excitability and confers neuroprotection in a manner similar to pregabalin” – was either misinterpreted or misquoted from my article, in which I make a similar statement (using the word “confer” rather than “confers”). Although the syntactical difference is slight, the ramifications are profound, and I thusly feel that this statement requires further clarification

Discovery of Novel Pain Genes Using Systems Genetics

Sensitivity to pain varies widely between subjects, and the significant influence of genetic factors on pain sensitivity variability is now widely appreciated. Animal models are a powerful tool for discovering genes influencing human pain sensitivity. Approximately 350 pain-related genes have been identified in the laboratory mouse to date, along with 14 pain-related quantitative trait loci (QTL) believed to contain genes involved in both acute and chronic pain response. Currently, the field of pain genetics is still heavily focused on the functional characterization of individual genes selected based on a-priori information, narrowing the focus of pain research to specific classes of protein-coding genes. In many cases, known pain genes exert relatively large phenotypic effects and are involved in numerous physiological processes, often limiting their use as therapeutic targets. This thesis had two immediate goals: 1) Identify novel genes whose allelic variants affect sensitivity to acute thermal pain, and 2) Understand the potential relationship of these new genes to existing pain genes and uncover new pathways involved in pain response. In order to accomplish the first goal, phenotypic data from the hot plate assay of thermal nociception were used to conduct two genome-wide in-silico genetic mapping studies – one in a population of emerging Diversity Outbred (DO) mice, and one in a population of Mouse Diversity Panel (MDP) mice. Candidate genes identified through genetic mapping were then assessed for relevance to pain by combining annotation data from a variety of publicly available data sources. Genetic network analysis tools were then used to visualize known and predicted functional relationships between candidate genes and other nervous system genes. This work identified three novel candidate pain genes: 1) the currently unclassified gene RIKEN cDNA C230014O12 (C230014O12Rik), and the protein coding genes 2) glypican 3 (Gpc3) and 3) hydrocephalus inducing (Hydin). Subsequent genetic network analyses revealed that the candidate genes may function in novel pain-related biological pathways. The information generated by this research promises to facilitate the long term goal of developing improved methods of individualized acute, and perhaps chronic, pain prevention and treatment

Combined use of pregabalin and memantine in fibromyalgia syndrome treatment: A novel analgesic and neuroprotective strategy?

Fibromyalgia syndrome (FMS) is a chronic widespread pain syndrome that is estimated to affect 4–8 million US adults. The exact molecular mechanisms underlying this illness remain unclear, rendering most clinical treatment and management techniques relatively ineffective. It is now known that abnormalities in both nociceptive and central pain processing systems are necessary (but perhaps not sufficient) to condition the onset and maintenance of FMS. These same systemic abnormalities are thought to be responsible for the loss of cephalic gray matter density observed in all FMS patients groups studied to date. The current scope of FMS treatment focuses largely on analgesia and does not clearly address potential neuroprotective strategies. This article proposes a combined treatment of pregabalin and memantine to decrease the pain and rate of gray matter atrophy associated with FMS. This dual-drug therapy targets the voltage-gated calcium ion channel (VGCC) and the N-methyl d-aspartate receptor (NMDAR) (respectively), two primary components of the human nociceptive and pain processing systems

Comparison between dynamic [18F]Fluoroethyltyrosine PET/CT and advanced MRI in cerebral high and low grade gliomas.\ua0 ;\ua0

Comparison between dynamic [18F]Fluoroethyltyrosine PET/CT and advanced MRI in cerebral high and low grade gliomas L. Picori, U. Rozzanigo, D. Donner, M. Erini, P. Feraco, M. Recla, F. Chierichetti; Santa Chiara Hospital, Trento, ITALY. Aim/Introduction: To investigate if dynamic [18F]fluoroethyl- L-tyrosine [18F]FET PET/CT improves the diagnosis in patients with suspected new or recurrent cerebral gliomas, respect to advanced MRI techniques. Materials and Methods: We retrospectively evaluated 20 patients who performed [18F] FET by a PET/CT tomograph: 15 had an indeterminate brain lesion, 5 a suspect glioma recurrence. All patients underwent a 40 minutes dynamic [18F]FET PET/CT acquisition and two different sequences, between 5-15 minutes and 20-30 minutes. For dynamic studies time-activity and time to peak curves were extracted using different region-of-interest (ROIs) and volume of interest (VOIs) definitions. MRI was performed with a 1.5T scanner just before [18F]FET-PET/CT using perfusion (PWI) and diffusion (DWI) weighted imaging: afterwards rCBV and ADC values were calculated placing the VOIs on the solid components of the lesion. In case of doubt (13 cases) single-voxel MR spectroscopy was performed. Multimodality imaging by fusion of PET/CT and different MRI sequences was performed for a joint assessment (radiologist and nuclear physician). Results: Final diagnosis was based on histology in 8 patients who underwent neurosurgery (5 HGG, 3 LGG) and on follow-up imaging in 12 patients (8 tumor progression, 4 stable benign lesion). On the basis of [18F]FET- PET, 7 cases were classified as high uptake (2 glioma recurrence and 5 new diagnosis of HGG tumor), 8 as low uptake (4 glioma recurrence, 2 new diagnosis of LGG tumor, 1 tumor progression, 1 tumefactive demielinating lesion) and 5 as no uptake (1 new diagnosis of LGG tumor, 4 stable benign lesion). Sensibility for dynamic [18F]FET-PET was 93% and specificity was 80%. Multiparametric MRI was in agreement with [18F]FET-PET in all 7 cases of high uptake and in 5 cases of low uptake. [18F]FET- PET helped to classify 6 MRI indeterminate lesions (2 suspect radionecrosis with pathologic uptake, 4 benign lesions without uptake). In 2 cases there was a discrepancy between MRI and PET: 1 tumefactive demielinating lesion was classified by [18F] FET as low uptake lesion, 1 LGG confirmed at histology showed no uptake. Conclusion: In our experience, adding quantitative data, such as dynamic acquisition in PET/CT by aminoacid tracer like [18F]FET, to rCBV and ADC maps in advanced MRI is crucial for a better comprehension of tumor lesions and to assess grading. Dynamic [18F]FET-PET/CT and multiparametric MR imaging have a very high sensibility to detect new tumoral lesions or suspect glioma recurrence. Agreement between PET and MRI is essential to improve diagnostic specificity. References: None