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Роль альфа-рецептора, активированного пероксидисом, в нейродегенеративных заболеваниях и других неврологических расстройствах: перспективы клинического применения.

Альфа-рецептор, активированный с помощью пероксисом, является членом сверхсемейства суперрецептора ядерного гормона и функционирует в качестве коэффициента транскрипции, связанного с регулированием клеточного метаболизма. Предыдущие исследования показали, что PPARα играет ключевую роль в возникновении и развитии нейродегенеративных заболеваний. Таким образом, альфа-агонисты, работающие на рецепторах, привлекают все большее внимание в качестве потенциальных средств лечения неврологических расстройств. Цель этого обзора состоит в том, чтобы прояснить прогресс в области исследований, касающихся п

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… Furthermore, the PPARα agonist fenofibrate, when combined with oxaliplatin, tends to prevent the enhancement of thermal hyperalgesia in hind paw withdrawal and friction responses induced by oxaliplatin. … Chemotherapy-induced hyperalgesia In vivo Caillaud et al., 2021; Aliyah et al., 2023 Negatively regulates NF-κB and AP-1 pathways. Radiation-induced brain injury In vivo Ramanan et al., 2008, 2009 Promotes myelination in zebrafish by activating SREBFs. …

Long-Term Outcomes of Pituitary Gland Preservation in Pituitary Macroadenoma Apoplexy: Case Series and Review of the Literature.

Introduction  For patients presenting with neurological changes from pituitary tumor apoplexy, urgent surgical intervention is commonly performed for diagnosis, tumor resection, and optic apparatus decompression. Although identification and preservation of the pituitary gland during the time of surgery can be challenging, it may lead to improve endocrine outcomes. Methods  A retrospective case series of all patients with macroadenomas presenting with apoplexy at Loyola University Medical Center from 2016 to 2018 was studied. Demographic, radiographic, and intraoperative characteristics were co

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… that CLBP may be associated to decreased descending inhibitory modulation of pain. 28 – 34 , 89 , 90 Although subtle pathological changes in peripheral and central nervous system are hard to be confirmed clinically, they still may explain sensory and neurological abnormalities including mechanical hyperalgesia … Patients with knee osteoarthritis who score highly on the PainDETECT questionnaire present with multimodality hyperalgesia, increased pain, and impaired physical function . Clin J Pain . 2018 ; 34 : 15 – 21 . doi: 10.1097/AJP.0000000000000504 28379872 PMC5728591 35. …

Mechanisms of Chemotherapy-Induced Neurotoxicity.

Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients' quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide ana

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… Neuropathic pain is characterized by the presence of allodynia and hyperalgesia due to the decrease of the sensitivity threshold for non-noxious and noxious stimuli, respectively. Remarkably, also spontaneous pain can be present in some patients. … Whilst adrenalectomy and corticoid receptor downregulation reduced and prevented oxaliplatin-induced hyperalgesia in both sexes, the downregulation of β 2 adrenergic receptor prevented and reversed oxaliplatin-induced hyperalgesia only in males. …

Sodium channel Na(v)1.7 is essential for lowering heat pain threshold after burn injury.

Marked hypersensitivity to heat and mechanical (pressure) stimuli develop after a burn injury, but the neural mechanisms underlying these effects are poorly understood. In this study, we establish a new mouse model of focal second-degree burn injury to investigate the molecular and cellular basis for burn injury-induced pain. This model features robust injury-induced behavioral effects and tissue-specific altered cytokine profile, but absence of glial activation in spinal dorsal horn. Three voltage-gated sodium channels, Na(v)1.7, Na(v)1.8, and Na(v)1.9, are preferentially expressed in periphe

Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities.

Rheumatoid arthritis is a common autoimmune disease that results from the deposition of antibodies-autoantigens in the joints, leading to long-lasting inflammation. The main features of RA include cartilage damage, synovial invasion and flare-ups of intra-articular inflammation, and these pathological processes significantly reduce patients' quality of life. To date, there is still no drug target that can act in rheumatoid arthritis. Therefore, the search for novel drug targets has become urgent. Due to their unique physicochemical properties, calcium ions play an important role in all cellula

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… These results all suggest that a decrease in pH during joint inflammation may activate the ASIC3 channels expressed on innervated neurons, thereby transmitting pain signals to the center, manifesting as nociceptive hyperalgesia. … Role of ASIC3 in the primary and secondary hyperalgesia produced by joint inflammation in mice Pain 2008 137 662 669 10.1016/j.pain.2008.01.020 18343037 PMC2756650 68. Kolker S.J. Walder R.Y. Usachev Y. Hillman J. Boyle D.L. Firestein G.S. Sluka K.A. …

Pain Management in Patients with Multiple Myeloma: An Update.

Most patients with multiple myeloma (MM) suffer from chronic pain at every stage of the natural disease process. This review focuses on the most common causes of chronic pain in MM patients: (1) pain from myeloma bone disease (MBD); (2) chemotherapy-induced peripheral neuropathy as a possible consequence of proteasome inhibitor therapy (i.e., bortezomib-induced); (3) post-herpetic neuralgia as a possible complication of varicella zoster virus reactivation because of post-transplantation immunodepression; and (4) pain in cancer survivors, with increasing numbers due to the success of antiblasti

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… LNP always reflects a peripheral nerve lesions which is dermatomal in distribution, does not cross the midline, and can be associated with positive sensory phenomena such as spontaneous burning pain, allodynia, and hyperalgesia [ 86 ]. … Superficial and localized pain presenting with positive phenomena such as allodynia and hyperalgesia is a strong outcome predictor of success. …

Analgesic Alkaloids Derived From Traditional Chinese Medicine in Pain Management.

Chronic pain is one of the most prevalent health problems. The establishment of chronic pain is complex. Current medication for chronic pain mainly dependent on anticonvulsants, tricyclic antidepressants and opioidergic drugs. However, they have limited therapeutic efficacy, and some even with severe side effects. We turned our interest into alkaloids separated from traditional Chinese medicine (TCM), that usually act on multiple drug targets. In this article, we introduced the best-studied analgesic alkaloids derived from TCM, including tetrahydropalmatine, aloperine, oxysophocarpine, matrine

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… In addition, superoxide dismutase analogs showed similar effects (reducing inflammation and hyperalgesia) by eliminating ROS ( Gao et al., 2007 ). 3.2.3 Downregulation of Glial Cell Activity Glial cells (microglial cells and astrocytes), are the most abundant and widely distributed cells which comprises … Antinociceptive effect of tetrandrine on LPS-induced hyperalgesia is mediated by the inhibition of IKKβ phosphorylation and the COX-2/PGE2 pathway in mice (Dosage: 1 × 10 −8 , 1 × 10 −7 , 1 × 10 −6 mol/L; Control: blank) ( Zhao et al., 2014 ). In addition, tetrandrine has antioxidant activities. …

Neuropathic Pain Related with Spinal Disorders: A Systematic Review.

Systematic literature review. To review the evidence from high-quality studies regarding the treatment of neuropathic pain originating specifically from spinal disorders. In general, treatment guidelines for neuropathic pain cover all its various causes, including medical disease, peripheral neuropathy, and cancer. However, the natural history of neuropathic pain originating from spinal disorders may differ from that of the pain originating from other causes or lesions. An expert research librarian used terms related to neuropathic pain and spinal disorders, disc herniation, stenosis, and spin

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… This evidence could be helpful in case of long-term users of opioids, and the adverse effects of their long-term use, such as abuse, addiction, hormonal abnormalities, and paradoxical hyperalgesia, should also be considered. … Ketamine, an N-methyl-D-aspartate receptor antagonist, could also be an option for patients with intractable pain even proactive medicatin or opioid-induced hyperalgesia. …

Differences in the Analgesic Effect of Opioids on Pain in Cancer Patients With Spinal Metastases.

BACKGROUND: Spinal metastasis pain includes both inflammatory and neuropathic pain, and opioids, which have only a μ-opioid receptor-stimulating effect, are generally less effective in neuropathic pain. However, no previous study has been conducted for the comparisons of the efficacy of opioids in treating spinal metastasis pain. OBJECTIVE: To compare the efficacy of tapentadol and methadone with other opioids for back pain caused by a metastatic spinal tumor. DESIGN: Retrospective cohort study. SETTING/SUBJECTS: A total of 274 patients were enrolled, who started a tapentadol extended-relea

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… Glutamate released from cancer cells that give rise to bone cancer excites and induces skeletal and cutaneous hyperalgesia and mechanical sensitization by potentially activating peripherally expressed NMDA receptors. 23 NMDA receptor antagonists have been reported effective for such neuropathic pain, … Therefore, some of the NRS reduction in the methadone group might be due to its effect on opioid-induced hyperalgesia through NMDA antagonism. …

Лекарства для борьбы с центральной нервной болью в результате лежащих в ее основе условий - систематический обзор.

В ходе этого систематического обзора была проведена оценка нынешней литературы, касающейся анальгетического лечения центральной нейропотической боли (КНБ) в условиях центральной нервной системы (КНС), таких, как повреждения спинного мозга, множественный склероз, посттравматические расстройства и болезнь Паркинсона. Цель этого систематического обзора заключалась в сопоставлении нынешнего алгоритмического подхода к УНП, который, как правило, не носит дискриминационного характера между основополагающими условиями, с тем, чтобы РСТ изучали рекомендованные алгоритмом и нерекомендуемые лекарственные

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… Clinical symptoms are presented as allodynia, hyperalgesia, burning pain, and others [ 3 , 7 ]. … Complex Regional Pain Syndrome (CRPS) Score/Shoulder–Hand Syndrome Score Three-subcategory questionnaire (Sensory: pain, hyperalgesia; Autonomic: distal edema; Motoric: painless passive range of motion) scored from 0 (no/none) up to 5 (most/massive). A total of 0–18 points is possible [ 31 ]. …

Wnt/Ryk signaling contributes to neuropathic pain by regulating sensory neuron excitability and spinal synaptic plasticity in rats.

Treating neuropathic pain continues to be a major clinical challenge and underlying mechanisms of neuropathic pain remain elusive. We have recently demonstrated that Wnt signaling, which is important in developmental processes of the nervous systems, plays critical roles in the development of neuropathic pain through the β-catenin-dependent pathway in the spinal cord and the β-catenin-independent pathway in primary sensory neurons after nerve injury. Here, we report that Wnt signaling may contribute to neuropathic pain through the atypical Wnt/Ryk signaling pathway in rats. Sciatic nerve injur

Exploring Serum Biomarkers for Neuropathic Pain in Rat Models of Chemotherapy-Induced Peripheral Neuropathy: A Comparative Pilot Study with Oxaliplatin, Paclitaxel, Bortezomib, and Vincristine.

Blood biomarkers, including neurofilament light chain (NfL), have garnered attention as potential indicators for chemotherapy-induced peripheral neuropathy (CIPN), a dose-limiting adverse effect of neurotoxic anticancer drugs. However, no blood biomarker has been established for routine application or translational research. This pilot study aimed to evaluate a limited panel of blood biomarkers in rat models of CIPN and their correlations with neuropathic pain. CIPN models were induced through repeated injections of oxaliplatin, paclitaxel, bortezomib, and vincristine. Electronic von Frey test

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… Cremophor ® EL has previously been identified as a potential neurotoxic agent in rats, leading to mechanical hyperalgesia and allodynia, which are associated with peripheral axonal damage [ 57 ]. … Thermal Hyperalgesia as a Marker of Oxaliplatin Neurotoxicity: A Prospective Quantified Sensory Assessment Study Pain 2009 144 245 252 10.1016/j.pain.2009.03.024 19457614 17. Boyette-Davis J.A. Cata J.P. Zhang H. Driver L.C. Wendelschafer-Crabb G. Kennedy W.R. Dougherty P.M. …

B12 as a Treatment for Peripheral Neuropathic Pain: A Systematic Review.

Neuropathic pain describes a range of unpleasant sensations caused by a lesion or disease of the somatosensory nervous system. The sensations caused by neuropathic pain are debilitating and improved treatment regimens are sought in order to improve the quality of life of patients. One proposed treatment for neuropathic pain is vitamin B12, which is thought to alleviate pain by a number of mechanisms including promoting myelination, increasing nerve regeneration and decreasing ectopic nerve firing. In this paper, the evidence for B12 as a drug treatment for neuropathic pain is reviewed. Twenty

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… Evoked pain encompasses allodynia which, is a painful perception in response to non-noxious stimuli and hyperalgesia, which is an exaggerated response to a noxious stimulus [ 2 ]. … Term A was pain or burning or allodynia or dysesthesia or dysesthesia or hyperalgesia or painful. Term B was cobalamin or cyanocobalamin or methylcobalamin or adenosylcobalamin or B12 or hydroxocobalamin. An English language filter was applied in our search. 2.2. …

Differential control of opioid antinociception to thermal stimuli in a knock-in mouse expressing regulator of G-protein signaling-insensitive Gαo protein.

Regulator of G-protein signaling (RGS) proteins classically function as negative modulators of G-protein-coupled receptor signaling. In vitro, RGS proteins have been shown to inhibit signaling by agonists at the μ-opioid receptor, including morphine. The goal of the present study was to evaluate the contribution of endogenous RGS proteins to the antinociceptive effects of morphine and other opioid agonists. To do this, a knock-in mouse that expresses an RGS-insensitive (RGSi) mutant Gαo protein, Gαo(G184S) (Gαo RGSi), was evaluated for morphine or methadone antinociception in response to noxio

Радиологическое представление Доусона о повторном переводе нескольких склерозов у молодой женщины: отчет о деле и обзор литературы.

В Соединенном Королевстве распространенность множественного склероза является одной из самых высоких в мире, причем в северной части Шотландии этот показатель является самым высоким. Патологически множественный склероз рассматривается как многофукаловые области демиелинации, приводящие к спектру клинических проявлений, которые создают диагностические проблемы. Пальцы Доусона - это перивентральные гиперинтенсивности, которые демонстрируют высокую специфичность для множественных склерозов по всем другим демиелинизирующим условиям. Захватывающе, что они также видны в церебральных заболеваниях мал

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… The presenting symptom started in the lower leg with pins and needle sensation as well as hyperalgesia. There was a slow progression of symptoms in a distal to proximal direction. Of note, right leg symptoms subsided prior to right arm symptoms emerging. Dysesthesia also involved tongue and face. …

Impaired PIEZO1 function drives uterine hypercontractility in adenomyosis-associated dysmenorrhea.

STUDY QUESTION: Does PIEZO1 play any role in adenomyosis-associated dysmenorrhea? SUMMARY ANSWER: PIEZO1 downregulation in the myometrium r … to increased uterine contractile amplitude and irregularity, accompanied by progressive generalized hyperalgesia. Additionally, increased myometrial vasopressin receptor (VP1αR) and potentially prostaglandin F2α (PGF2α) may also contribute to uterine hyperactivity. STUDY DESIGN SIZE AND DURATION: After written informed consent, we collected myometrial tissues …

Эффективность лазерной фотореактивной модуляции в управлении тригеминальной невралгией: систематический обзор и мета-анализ.

Настоящее систематическое обзорное исследование посвящено оценке эффективности лазерной фотобиомодуляции (ПБМ) в снижении боли у пациентов с тригеминальной невралгией и постгерпетической невралгией. Случайные контролируемые клинические испытания были идентифицированы через поиск в следующих базах данных: PubMed, Web of Science, LILACS, EMBASE, Scopus и Cochrane Library. Нет исследований, вовлекающих пациентов с постгерпетической невралгией, которые соответствовали критериям включения и были поэтому исключены. Включено девять исследований, включающих итого 387 пациентов с диагнозом тригеминальн

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… It is characterized by hyperalgesia and allodynia, in addition to a limited response to non-steroidal anti-inflammatory drugs (NSAIDs) [ 5 – 7 ]. Its global prevalence is estimated to range between 7% and 10% [ 1 ]. … In the facial region, it frequently involves the ophthalmic division of the trigeminal nerve, resulting in severe pain, burning sensations, hyperalgesia, and allodynia [ 13 ]. …

Small-Fiber Neuropathy: An Etiology-Oriented Review.

BackgroundSmall-fiber neuropathy (SFN), affecting Aδ or C nerve fibers, is characterized by alterations of pain and temperature sensation, as well as autonomic dysfunction. Its diagnosis may still remain challenging as methods specifically assessing small nerve fibers are not always readily available, and standard techniques for large-fiber neuropathies, such as electroneuromyography, yield negative results. Still, skin biopsy for epidermal innervation and quantitative sensory testing allow for diagnosis in the presence of a congruent clinical picture.ObjectivesMany different etiologies may un

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… In particular, microneurography has provided insight into pain-related phenomena such as hyperalgesia [ 39 ]. Thus, while not readily applicable to clinical practice, it represents a key technique for research applications. 4. … Two types of C nociceptors in human skin and their behavior in areas of capsaicin-induced secondary hyperalgesia J. Neurophysiol. 2004 91 2770 2781 10.1152/jn.00565.2003 14762154 40. Sumner C.J. Sheth S. Griffin J.W. Cornblath D.R. Polydefkis M. …

Внеклеточные нуклеотиды являются посредником в вирусных инфекциях центральной нервной системы: ключи от нейроинфламмации и нейродегенерации.

Недавний рост инфекционных заболеваний, затрагивающих центральную нервную систему, вызвал обеспокоенность по поводу их роли в нейроинфламмации и нейродегенерации. Вирусные патогены или их продукты могут вторгаться в центральную нервную систему и вызывать повреждения, ведущие к менингиту, энцефалиту, менингоэнцефалиту, миелиту или постинфекционным демиелинизирующим заболеваниям. Хотя изначально нейроинфламмация имеет защитную функцию, хроническое воспаление может способствовать развитию нейродегенеративных заболеваний. Такие механизмы, как агрегация белков и клеточные расстройства, связаны с ко

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… Its downregulation with RNA interference technique (the short hairpin RNA, shRNA) relieved mechanical and thermal hyperalgesia following the gp120 challenge, forms of heightened sensitivity to pain commonly associated with neuropathic pain (Yi et al., 2018). … In the same rat model, the P2X7 receptor was upregulated, and its antagonist, Brilliant Blue G (BBG), downregulated the receptor expression and the hyperalgesia (Wu et al., 2017). …

A Randomized Placebo-Controlled Trial of the Anti-Nerve Growth Factor Antibody Tanezumab in Subjects With Cancer Pain Due to Bone Metastasis.

BackgroundThis phase III, randomized, double-blind, placebo-controlled, parallel-group study assessed the efficacy and safety of tanezumab in subjects with cancer pain predominantly due to bone metastasis receiving background opioid therapy.MethodsSubjects were randomized (stratified by (1) tumor aggressiveness and (2) presence/absence of concomitant anticancer treatment) to placebo or tanezumab 20 mg. Treatment was administered by subcutaneous injection every 8 weeks for 24 weeks (3 doses) followed by a 24-week safety follow-up period. The primary outcome was change in daily average pain in t

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… signaling has short- and long-term effects on the activity and/or expression of pro-nociceptive ion channels, receptors, and peptides, which results in increased nociceptive signaling in the periphery (peripheral sensitization) and dorsal horn of the spinal cord (central sensitization) that presents as hyperalgesia … . 8 , 9 Sprouting of nerve fibers may also contribute to this hyperalgesia since, in animal models of bone cancer pain, NGF promotes substantial increases in the density of nociceptors in bone via local neuronal sprouting of TrkA+ fibers and promotes formation of painful neuroma-like structures. 25-27 …