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Chronic pain pathologies, which are due to maladaptive changes in the peripheral and/or central nervous systems, are debilitating diseases that affect 20% of the European adult population. A better understanding of the mechanisms underlying this pathogenesis would facilitate the identification of novel therapeutic targets. Functional connectivity (FC) extracted from coherent low-frequency hemodynamic fluctuations among cerebral networks has recently brought light on a powerful approach to study large scale brain networks and their disruptions in neurological/psychiatric disorders. Analysis of FC is classically performed on averaged signals over time, but recently, the analysis of the dynamics of FC has also provided new promising information. Keeping in mind the limitations of animal models of persistent pain but also the powerful tool they represent to improve our understanding of the neurobiological basis of chronic pain pathogenicity, this study aimed at defining the alterations in functional connectivity, in a clinically relevant animal model of sustained inflammatory pain (Adjuvant-induced Arthritis) in rats by using functional ultrasound imaging, a neuroimaging technique with a unique spatiotemporal resolution (100 μm and 2 ms) and sensitivity. Our results show profound alterations of FC in arthritic animals, such as a subpart of the somatomotor (SM) network, occurring several weeks after the beginning of the disease. Also, we demonstrate for the first time that dynamic functional connectivity assessed by ultrasound can provide quantitative and robust information on the dynamic pattern that we define as brain states. While the main state consists of an overall synchrony of hemodynamic fluctuations in the SM network, arthritic animal spend statistically more time in two other states, where the fluctuations of the primary sensory cortex of the inflamed hind paws show asynchrony with the rest of the SM network. Finally, correlating FC changes with pain behavior in individual animals suggest links between FC alterations and either the cognitive or the emotional aspects of pain. Our study introduces fUS as a new translational tool for the enhanced understanding of the dynamic pain connectome and brain plasticity in a major preclinical model of chronic pain.
Learn More >To determine whether cervical cord levels of metabolites are associated with pain sensation after spinal cord injury (SCI), we performed magnetic resonance spectroscopy in SCI patients with and without neuropathic pain (NP).
Learn More >Chronic musculoskeletal pain is one of the main causes of years lived with disability and generates the highest cost of health care among chronic pain conditions. Internet-based treatments have been shown to be an alternative for the treatment of musculoskeletal conditions, in addition to reducing barriers such as travel, high demands on the public health system, lack of time, lack of insurance coverage for private care, and high costs for long-term treatment. The aim of this clinical trial is to develop and test the effectiveness and cost-effectiveness of, an internet-based self-management program based on pain education and exercise for people with chronic musculoskeletal pain.
Learn More >Introduction Neuropathic pain disorders are diverse, and the currently available therapies are ineffective in the majority of cases. Therefore, there is a major need for gaining novel mechanistic insights and developing new treatment strategies for neuropathic pain. Areas covered We performed an in-depth literature search on the molecular mechanisms and systemic importance of the ceramide-to-S1P rheostat regulating neuron function and neuroimmune interactions in the development of neuropathic pain. Expert Opinion The S1P receptor modulator FTY720 (fingolimod, Gilenya®), LPA receptor antagonists and several mechanistically related compounds in clinical development raise great expectations for treating neuropathic pain disorders. Research on S1P receptors, S1P receptor modulators or SPHK inhibitors with distinct selectivity, pharmacokinetics and safety must provide more mechanistic insight into whether they may qualify as useful treatment options for neuropathic pain disorders. The functional relevance of genetic variations within the ceramide to S1P rheostat should be explored for an enhanced understanding of neuropathic pain pathogenesis. The ceramide to S1P rheostat is emerging as a critically important regulator hub of neuroimmune interactions along the pain pathway, and improved mechanistic insight is required to develop more precise and effective drug treatment options for patients suffering from neuropathic pain disorders.
Learn More >Neuromodulation is a treatment option for people suffering from painful diabetic neuropathy (PDN) unresponsive to conventional pharmacotherapy. We systematically examined the pain outcomes of patients with PDN receiving any type of invasive neuromodulation for treatment of neuropathic pain.
Learn More >To explore the usefulness and feasibility of a comprehensive vocational rehabilitation (C-VR) program and less comprehensive (LC-VR) program for workers on sick leave due to chronic musculoskeletal pain, from the perspective of patients, professionals, and managers. Semi-structured interviews were held with patients, professionals, and managers. Using topic lists, participants were questioned about barriers to and facilitators of the usefulness and feasibility of C-VR and LC-VR. Thirty interviews were conducted with thirteen patients ( = 6 C-VR, = 7 LC-VR), eight professionals, and nine managers. All interviews were transcribed verbatim. Data were analyzed by systematic text condensation using inductive thematic analysis. Three themes emerged for usefulness ("patient factors," "content," "dosage") and six themes emerged for feasibility ("satisfaction," "intention to continue use," "perceived appropriateness," "positive/negative effects on target participants," "factors affecting implementation ease or difficulty," "adaptations"). The patients reported that both programs were feasible and generally useful. The professionals preferred working with the C-VR, although they disliked the fixed and uniform character of the program. They also mentioned that this program is too extensive for some patients, and that the latter would probably benefit from the LC-VR program. Despite their positive intentions, the managers stated that due to the Dutch healthcare system, implementation of the LC-VR program would be financially unfeasible. The main conclusion of this study is that it is not useful to have one VR program for all patients with CMP and reduced work participation, and that flexible and tailored-based VR are warranted.Implications for rehabilitationBoth comprehensive and less comprehensive vocational rehabilitation are deemed useful for patients with chronic musculoskeletal pain and reduced work participation. Particular patient factors, for instance information uptake, discipline, willingness to change, duration of complaints, movement anxiety, obstructing thoughts, and willingness to return to work might guide the right program for the right patient.Both comprehensive and less comprehensive vocational rehabilitation are deemed feasible in practice. However, factors such as center logistic (schemes, rooms, professionals available) and country-specific healthcare insurance and sickness compensation systems should foster the implementation of less comprehensive programs.
Learn More >Reduced blood or cerebrospinal fluid levels of allopregnanolone are involved in menstrual cycle-linked CNS disorders, such as catamenial epilepsy. This condition, like menstrually-related migraine, is characterized by severe, treatment-resistant attacks. We explored whether there were differences in allopregnanolone, progesterone and testosterone serum levels between women with menstrually-related migraine (MM, n = 30) or postmenopausal migraine without aura who had suffered from menstrually-related migraine during their fertile age (PM, n = 30) and non-headache control women in fertile age (FAC, n = 30) or post-menopause (PC, n = 30).
Learn More >To determine if pooled estimates of the prevalence of unexpected findings in patients with headache and normal neurologic examination support current expert opinion-based neuroimaging guidelines.
Learn More >Painful peripheral neuropathy affects millions of people worldwide. Peripheral neuropathy develops in patients with various diseases, including rare familial or acquired amyloid polyneuropathies, as well as some common diseases, including type 2 diabetes mellitus and several chronic inflammatory diseases. Intriguingly, these diseases share a histopathological feature-deposits of amyloid-forming proteins in tissues. Amyloid-forming proteins may cause tissue dysregulation and damage, including damage to nerves, and may be a common cause of neuropathy in these, and potentially other, diseases. Here, we will discuss how amyloid proteins contribute to peripheral neuropathy by reviewing the current understanding of pathogenic mechanisms in known inherited and acquired (usually rare) amyloid neuropathies. In addition, we will discuss the potential role of amyloid proteins in peripheral neuropathy in some common diseases, which are not (yet) considered as amyloid neuropathies. We conclude that there are many similarities in the molecular and cell biological defects caused by aggregation of the various amyloid proteins in these different diseases and propose a common pathogenic pathway for "peripheral amyloid neuropathies".
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