Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model

Abstract Neuroplasticity in the amygdala, a brain center for emotions, leads to increased neuronal activity and output that can generate emotional-affective behaviors and modulate nocifensive responses. Mechanisms of increased activity in the amygdala output region (central nucleus, CeA) include increased reactive oxygen species, and so we explored beneficial effects of monomethyl fumarate (MMF), which can have neuroprotective effects through the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) antioxidant response pathway. Systemic (intraperitoneal) MMF dose-dependently inhibited vocalizations and mechanosensitivity (hindlimb withdrawal reflexes) of rats in an arthritis pain model (kaolin-carrageenan-induced monoarthritis in the knee). Stereotaxic administration of MMF into the CeA by microdialysis also inhibited vocalizations but had a limited effect on mechanosensitivity, suggesting a differential contribution to emotional-affective vs sensory pain aspects. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that stereotaxic administration of MMF into the CeA by microdialysis inhibited background activity and responses of CeA neurons to knee joint stimulation in the arthritis pain model. Monomethyl fumarate had no effect on behaviors and neuronal activity under normal conditions. The results suggest that MMF can inhibit emotional-affective responses in an arthritis pain model through an action that involves the amygdala (CeA).
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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A 50-year-old female with history of rheumatoid arthritis presented with a large nodule on right medial knee. The lesion had been present for several years and was progressively growing causing her pain. Recently the lesion had begun to ulcerate and drain a yellow liquid. The patient was on methotrexate 20 mg weekly, hydroxychloroquine 200 mg daily, and prednisone 5 mg daily for her rheumatoid arthritis. On her right medial knee, she had a 6.8 cm soft, slightly compressible, yellowish nodule. The lesion was surgically resected under local anesthesia and the defect primarily repaired.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
Abstract The amygdala plays a critical role in emotional-affective aspects of behaviors and pain modulation. The central nucleus of amygdala (CeA) serves major output functions, and neuroplasticity in the CeA is linked to pain-related behaviors in different models. Activation of Gi/o-coupled group II metabotropic glutamate receptors (mGluRs), which consist of mGluR2 and mGluR3, can decrease neurotransmitter release and regulate synaptic plasticity. Group II mGluRs have emerged as targets for neuropsychiatric disorders and can inhibit pain-related processing and behaviors. Surprisingly, site and mechanism of antino...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research
For more than a century, clinicians have noticed a paradoxical phenomenon: certain patients who are taking opioids (which are supposed to numb pain) become more sensitive to pain than those who are not taking opioids. The earliest observation of this phenomenon can be traced back to the British physician Sir Clifford Allbutt, who, in 1870, described it: “at such times I have certainly felt it a great responsibility to say that pain, which I know is an evil, is less injurious than morphia, which may be an evil. Does morphia tend to encourage the very pain it pretends to relieve?” Research studies and clinical ob...
Source: Harvard Health Blog - Category: Consumer Health News Authors: Tags: Pain Management Source Type: blogs
CONCLUSIONSIntra-articular corticosteroid injection practices in outpatient settings are heterogeneous. Septic arthritis following intra-articular injection was infrequent. We were unable to associate septic arthritis with mixing intra-articular injectables outside the pharmacy.
Source: American Journal of Infection Control - Category: Infectious Diseases Source Type: research
Conclusions: We report a facile radiolabeling procedure for the COX-2 ligand [18F]FMTP, in excellent purity and molar activity. [18F]FMTP showed moderate uptake and specific binding in COX-2 positive BxPC3 cells. MicroPET imaging in mice showed BBB penetration and fast washout in brain due to low concentration of COX-2 in normal brain. In vitro binding to COX-2 and the BBB permeability of [18F]FMTP indicate that it may be a useful PET tracer for in vivo imaging of COX-2 in neuroinflammation. Research support: Diane Goldberg Foundation (NYSPI/CUMC), NCATS UL1TR001873 (Reilly) Irving Institute/CTSA Translational Therapeutics Accelerator
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Preclinical Probes for Neuroimaging Posters Source Type: research
We describe a case of CPPDd in the TMJ of a 54-year-old Japanese woman who was referred to our hospital with the complaints of unpainful swelling in the right TMJ region and restricted mouth opening. Computed tomography (CT) and magnetic resonance imaging (MRI) showed 46 × 42-mm and 27 × 18-mm calcified masses in the right TMJ region. The masses were both outside and inside the mandibular condyle, both of which extended to the skull base. Since we suspected a tumor in the TMJ, the lesion was partially excised for biopsy with the patient under general anesthesia. The microscopic exami...
Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology - Category: ENT & OMF Source Type: research
We examined the expression of TRPV1 in peripheral tissue and DRG neurons of CPIP model rats and we studied whether CPIP model could induce peripheral sensitization of TRPV1 channel and enhance DRG neuron excitability. Then we examined the therapeutic effects of locally applied TRPV1 specific antagonist AMG9810 on pain responses of CPIP model rats. Lastly, we explored the effects of AMG9810 on DRG neuron hyperexcitability and spinal glial activation induced by CPIP. Our results demonstrate that TRPV1 plays an important role in mediating the behavioral hypersensitivity of CPIP model rats via promoting peripheral nociceptor a...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion: These findings support the hypothesis that in FM a deteriorated function of cortical inhibition, indexed by a higher SICI parameter, a lower function of the DPMS, together with a higher level of BDNF indicate that FM has different pathological substrates from depression. They suggest that an up-regulation phenomenon of intracortical inhibitory networks associated with a disruption of the DPMS function occurs in FM. Introduction Major depressive disorder (MDD) and fibromyalgia (FM) present overlapped symptoms. Although the connection between these two disorders has not been elucidated yet, the disruption...
Source: Frontiers in Human Neuroscience - Category: Neuroscience Source Type: research
In this study, we evaluated the effect of auranofin on the radiosensitivity of intestinal epithelial cells. The treatment with a combination of 1 μM auranofin and 5 Gy ionizing radiation showed clear additive effects on caspase 3 cleavage and apoptotic DNA fragmentation in IEC-6 cells, and auranofin administration significantly aggravated the radiation-induced intestinal injury in mice. Auranofin treatment also resulted in the activation of the unfolded protein response and in the inhibition of thioredoxin reductase, which is a key component of the cellular antioxidant system. Pre-treatment with N-acetyl cysteine, a wel...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion: The present study suggests that the extract of LMZ attenuates CFA-induced inflammatory pain by suppressing the ERK1/2 and NF-κB signaling pathway at both peripheral and central level. Introduction Pain is one of the most common symptoms in clinical practice, and inflammatory pain is the most important type of pain (Patapoutian et al., 2009). Inflammatory pain is a growing global health problem. In generally, there is a common course of progression in inflammation and pain share. When patients experience inflammation, they may develop hyperalgesia or allodynia to various mechanical, thermal, or che...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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