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Science (New York, N.Y.) Nov 2016Acute pain is protective and a cardinal feature of inflammation. Chronic pain after arthritis, nerve injury, cancer, and chemotherapy is associated with chronic... (Review)
Review
Acute pain is protective and a cardinal feature of inflammation. Chronic pain after arthritis, nerve injury, cancer, and chemotherapy is associated with chronic neuroinflammation, a local inflammation in the peripheral or central nervous system. Accumulating evidence suggests that non-neuronal cells such as immune cells, glial cells, keratinocytes, cancer cells, and stem cells play active roles in the pathogenesis and resolution of pain. We review how non-neuronal cells interact with nociceptive neurons by secreting neuroactive signaling molecules that modulate pain. Recent studies also suggest that bacterial infections regulate pain through direct actions on sensory neurons, and specific receptors are present in nociceptors to detect danger signals from infections. We also discuss new therapeutic strategies to control neuroinflammation for the prevention and treatment of chronic pain.
Topics: Animals; Bacterial Infections; Chronic Pain; Ganglia, Spinal; Humans; Keratinocytes; Macrophages; Mice; Monocytes; Neoplasms; Neuritis; Neuroglia; Nociceptors; Pain; Rats; Spinal Cord; T-Lymphocytes; Toll-Like Receptors
PubMed: 27811267
DOI: 10.1126/science.aaf8924 -
Neurotherapeutics : the Journal of the... Oct 2021Neuropathy and related disabilities are the major medical consequences of leprosy, which remains a global medical concern. Despite major advances in understanding the... (Review)
Review
Neuropathy and related disabilities are the major medical consequences of leprosy, which remains a global medical concern. Despite major advances in understanding the mechanisms of M. leprae entry into peripheral nerves, most aspects of the pathogenesis of leprosy neuropathy remain poorly understood. Sensory loss is characteristic of leprosy, but neuropathic pain is sometimes observed. Effective anti-microbial therapy is available, but neuropathy remains a problem especially if diagnosis and treatment are delayed. Currently there is intense interest in post-exposure prophylaxis with single-dose rifampin in endemic areas, as well as with enhanced prophylactic regimens in some situations. Some degree of nerve involvement is seen in all cases and neuritis may occur in the absence of leprosy reactions, but acute neuritis commonly accompanies both Type 1 and Type 2 leprosy reactions and may be difficult to manage. A variety of established as well as new methods for the early diagnosis and assessment of leprosy neuropathy are reviewed. Corticosteroids offer the primary treatment for neuritis and for subclinical neuropathy in leprosy, but success is limited if nerve function impairment is present at the time of diagnosis. A candidate vaccine has shown apparent benefit in preventing nerve injury in the armadillo model. The development of new therapeutics for leprosy neuropathy is greatly needed.
Topics: Animals; Armadillos; Leprosy; Mycobacterium leprae; Neuritis; Peripheral Nervous System Diseases
PubMed: 34799845
DOI: 10.1007/s13311-021-01153-z -
International Journal of Molecular... Apr 2023Dysfunction of the immune system can result in damage of the peripheral nervous system. The immunological mechanisms, which include macrophage infiltration, inflammation... (Review)
Review
Dysfunction of the immune system can result in damage of the peripheral nervous system. The immunological mechanisms, which include macrophage infiltration, inflammation and proliferation of Schwann cells, result in variable degrees of demyelination and axonal degeneration. Aetiology is diverse and, in some cases, may be precipitated by infection. Various animal models have contributed and helped to elucidate the pathophysiological mechanisms in acute and chronic inflammatory polyradiculoneuropathies (Guillain-Barre Syndrome and chronic inflammatory demyelinating polyradiculoneuropathy, respectively). The presence of specific anti-glycoconjugate antibodies indicates an underlying process of molecular mimicry and sometimes assists in the classification of these disorders, which often merely supports the clinical diagnosis. Now, the electrophysiological presence of conduction blocks is another important factor in characterizing another subgroup of treatable motor neuropathies (multifocal motor neuropathy with conduction block), which is distinct from Lewis-Sumner syndrome (multifocal acquired demyelinating sensory and motor neuropathy) in its response to treatment modalities as well as electrophysiological features. Furthermore, paraneoplastic neuropathies are also immune-mediated and are the result of an immune reaction to tumour cells that express onconeural antigens and mimic molecules expressed on the surface of neurons. The detection of specific paraneoplastic antibodies often assists the clinician in the investigation of an underlying, sometimes specific, malignancy. This review aims to discuss the immunological and pathophysiological mechanisms that are thought to be crucial in the aetiology of dysimmune neuropathies as well as their individual electrophysiological characteristics, their laboratory features and existing treatment options. Here, we aim to present a balance of discussion from these diverse angles that may be helpful in categorizing disease and establishing prognosis.
Topics: Animals; Guillain-Barre Syndrome; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Polyneuropathies; Autoantibodies; Inflammation; Neuritis
PubMed: 37108447
DOI: 10.3390/ijms24087288 -
Nutrients Mar 2019Glial activation and neuroinflammation play significant roles in apoptosis as well as in the development of cognitive and memory deficits. Neuroinflammation is also a...
Glial activation and neuroinflammation play significant roles in apoptosis as well as in the development of cognitive and memory deficits. Neuroinflammation is also a critical feature in the pathogenesis of neurodegenerative disorders such as Alzheimer and Parkinson's diseases. Previously, hesperetin has been shown to be an effective antioxidant and anti-inflammatory agent. In the present study, in vivo and in vitro analyses were performed to evaluate the neuroprotective effects of hesperetin in lipopolysaccharide (LPS)-induced neuroinflammation, oxidative stress, neuronal apoptosis and memory impairments. Based on our findings, LPS treatment resulted in microglial activation and astrocytosis and elevated the expression of inflammatory mediators such as phosphorylated-Nuclear factor-κB (p-NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the cortical and hippocampal regions and in BV2 cells. However, hesperetin cotreatment markedly reduced the expression of inflammatory cytokines by ameliorating Toll-like receptor-4 (TLR4)-mediated ionized calcium-binding adapter molecule 1/glial fibrillary acidic protein (Iba-1/GFAP) expression. Similarly, hesperetin attenuated LPS-induced generation of reactive oxygen species/lipid per oxidation (ROS/LPO) and improved the antioxidant protein level such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Haem-oxygenase (HO-1) in the mouse brain. Additionally, hesperetin ameliorated cytotoxicity and ROS/LPO induced by LPS in HT-22 cells. Moreover, hesperetin rescued LPS-induced neuronal apoptosis by reducing the expression of phosphorylated-c-Jun N-terminal kinases (p-JNK), B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), and Caspase-3 protein and promoting the Bcl-2 protein level. Furthermore, hesperetin enhanced synaptic integrity, cognition, and memory processes by enhancing the phosphorylated-cAMP response element binding protein (p-CREB), postsynaptic density protein-95 (PSD-95), and Syntaxin. Overall, our preclinical study suggests that hesperetin conferred neuroprotection by regulating the TLR4/NF-κB signaling pathway against the detrimental effects of LPS.
Topics: Animals; Apoptosis; Citrus; Hesperidin; Hippocampus; Lipopolysaccharides; Male; Memory; Memory Disorders; Mice; Mice, Inbred C57BL; NF-kappa B; Neuritis; Neuroprotective Agents; Oxidative Stress; Signal Transduction; Toll-Like Receptor 4
PubMed: 30884890
DOI: 10.3390/nu11030648 -
Muscle & Nerve Jan 2023Neuralgic amyotrophy (NA), also referred to as idiopathic brachial plexitis and Parsonage-Turner syndrome, is a peripheral nerve disorder characterized by acute severe... (Review)
Review
Neuralgic amyotrophy (NA), also referred to as idiopathic brachial plexitis and Parsonage-Turner syndrome, is a peripheral nerve disorder characterized by acute severe shoulder pain followed by progressive upper limb weakness and muscle atrophy. While NA is incompletely understood and often difficult to diagnose, early recognition may prevent unnecessary tests and interventions and, in some situations, allow for prompt treatment, which can potentially minimize adverse long-term sequalae. High-resolution ultrasound (HRUS) has become a valuable tool in the diagnosis and evaluation of NA. Pathologic HRUS findings can be grouped into four categories: nerve swelling, swelling with incomplete constriction, swelling with complete constriction, and fascicular entwinement, which may represent a continuum of pathologic processes. Certain ultrasound findings may help predict the likelihood of spontaneous recovery with conservative management versus the need for surgical intervention. We recommend relying heavily on history and physical examination to determine which nerves are clinically affected and should therefore be assessed by HRUS. The nerves most frequently affected by NA are the suprascapular, long thoracic, median and anterior interosseous nerve (AIN) branch, radial and posterior interosseous nerve (PIN) branch, axillary, spinal accessory, and musculocutaneous. When distal upper limb nerves are affected (AIN, PIN, superficial radial nerve), the lesion is almost always located in their respective fascicles within the parent nerve, proximal to its branching point. The purpose of this review is to describe a reproducible, standardized, ultrasonographic approach for evaluating suspected NA, and to share reliable techniques and clinical considerations when imaging commonly affected nerves.
Topics: Humans; Brachial Plexus Neuritis; Peripheral Nerves; Peripheral Nervous System Diseases; Radial Nerve; Constriction, Pathologic; Shoulder Pain
PubMed: 36040106
DOI: 10.1002/mus.27705 -
Muscle & Nerve Dec 2022Hourglass-like constrictions (HGCs) occur in neuralgic amyotrophy (NA), but the earliest time at which they can be recognized by imaging is poorly understood. We aimed...
INTRODUCTION/AIMS
Hourglass-like constrictions (HGCs) occur in neuralgic amyotrophy (NA), but the earliest time at which they can be recognized by imaging is poorly understood. We aimed to determine the prevalence of abnormal imaging findings in the acute phase of NA.
METHODS
Magnetic resonance neurography (MRN) and high-resolution ultrasound (US) examinations were performed at five sites. The investigation included 39 patients with acute NA who underwent imaging within 31 days of symptom onset. Correlation between imaging and electromyography (EMG) findings was measured.
RESULTS
US was performed in 29 patients and MRN in 23; 16 patients underwent US only, 10 MRN only, and 13 had both. US and MRN showed nerve abnormalities within 1 mo from NA onset in 90% of patients. HGCs were found in 74% (29/39) of the patients: 4 within 1 wk, 8 within 2 wk, 5 within 3 wk, and 12 within 4 wk. The earliest HGC on US was found within 12 h, and on MRN within 3 days from symptom onset. MRN demonstrated a denervation edema pattern of affected muscles in 91% of the patients. The shortest time to observe an edema pattern on MRN was 8 days. EMG was performed in 30 patients and revealed fibrillation potentials in affected muscles in 22 (73%). A denervation edema pattern on MRN was significantly associated with the presence of HGCs both on MRN and US, and with fibrillation potentials on EMG.
DISCUSSION
In the early phase of NA, US and MRN are useful diagnostic techniques for demonstrating nerve abnormalities.
Topics: Humans; Brachial Plexus Neuritis; Ultrasonography; Magnetic Resonance Imaging; Nerve Tissue
PubMed: 36214185
DOI: 10.1002/mus.27732 -
PLoS Neglected Tropical Diseases Jun 2023Leprosy is caused by multiple interactions between Mycobacterium leprae (M. leprae) and the host's peripheral nerve cells. M. leprae primarily invades Schwann cells,...
BACKGROUND
Leprosy is caused by multiple interactions between Mycobacterium leprae (M. leprae) and the host's peripheral nerve cells. M. leprae primarily invades Schwann cells, causing nerve damage and consequent development of disabilities. Despite its long history, the pathophysiological mechanisms of nerve damage in the lepromatous pole of leprosy remain poorly understood. This study used the findings of 18F-FDG PET/CT on the peripheral nerves of eight lepromatous patients to evaluate the degree of glucose uptake by peripheral nerves and compared them with clinical, electrophysiological, and histopathological evaluations.
METHODS
Eight patients with lepromatous leprosy were included in this study. Six patients were evaluated up to three months after leprosy diagnosis using neurological examination, nerve conduction study, 18F-FDG PET/CT, and nerve biopsy. Two others were evaluated during an episode of acute neuritis, with clinical, neurophysiological, and PET-CT examinations to compare the images with the first six.
RESULTS
Initially, six patients already had signs of peripheral nerve injury, regardless of symptoms; however, they did not present with signs of neuritis, and there was little or no uptake of 18F-FDG in the clinically and electrophysiologically affected nerves. Two patients with signs of acute neuritis had 18F-FDG uptake in the affected nerves.
CONCLUSIONS
18F-FDG uptake correlates with clinical neuritis in lepromatous leprosy patients but not in silent neuritis patients. 18F-FDG PET-CT could be a useful tool to confirm neuritis, especially in cases that are difficult to diagnose, such as for the differential diagnosis between a new episode of neuritis and chronic neuropathy.
Topics: Humans; Leprosy, Lepromatous; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Leprosy; Mycobacterium leprae; Neuritis; Peripheral Nervous System Diseases; Inflammation; Glucose
PubMed: 37276237
DOI: 10.1371/journal.pntd.0011383 -
Deutsches Arzteblatt International Apr 2018
Topics: Humans; Leprosy; Neuritis; Polyneuropathies
PubMed: 29789111
DOI: 10.3238/arztebl.2018.0296b -
The Journal of Bone and Joint Surgery.... May 2008Neuralgic amyotrophy is an uncommon condition characterised by the acute onset of severe pain in the shoulder and arm, followed by weakness and atrophy of the affected...
Neuralgic amyotrophy is an uncommon condition characterised by the acute onset of severe pain in the shoulder and arm, followed by weakness and atrophy of the affected muscles, and sensory loss as the pain subsides. The diversity of its clinical manifestations means that it may present to a variety of different specialties within medicine. This article describes the epidemiology, aetiopathogenesis, clinical features, differential diagnoses, investigations, treatment, course and prognosis of the condition.
Topics: Adrenal Cortex Hormones; Analgesics; Brachial Plexus Neuritis; Diagnosis, Differential; Humans; Prognosis
PubMed: 18450616
DOI: 10.1302/0301-620X.90B5.20411 -
PLoS Neglected Tropical Diseases Apr 2022Leprosy is still a prevalent disease in Brazil, representing 93% of all occurrences in the Americas. Leprosy neuropathy is one of the most worrying manifestations of the...
Leprosy is still a prevalent disease in Brazil, representing 93% of all occurrences in the Americas. Leprosy neuropathy is one of the most worrying manifestations of the disease. Acute neuropathy usually occurs during reaction episodes and is called neuritis. Twenty-two leprosy patients were included in this study. These patients had neural pain associated with ulnar sensory neuropathy, with or without adjunct motor involvement. The neurological picture began within thirty days of the clinical evaluation. The patients underwent a nerve conduction study and the demyelinating findings confirmed the diagnosis of neuritis. Ultrasonographic study (US) of the ulnar nerve was performed in all patients by a radiologist who was blinded to the clinical or neurophysiological results. Morphological characteristics of the ulnar nerve were analyzed, such as echogenicity, fascicular pattern, transverse cross-sectional area (CSA), aspect of the epineurium, as well as their anatomical relationships. The volume of selected muscles referring to the ulnar nerve, as well as their echogenicity, was also examined. Based on this analysis, patients with increased ulnar nerve CSA associated with loss of fascicular pattern, epineurium hyperechogenicity and presence of power Doppler flow were classified as neuritis. Therefore, patients initially classified by the clinical-electrophysiological criteria were reclassified by the imaging criteria pre-established in this study as with and without neuritis. Loss of fascicular pattern and flow detection on power Doppler showed to be significant morphological features in the detection of neuritis. In 38.5% of patients without clinical or neurophysiological findings of neuritis, US identified power Doppler flow and loss of fascicular pattern. The US is a method of high resolution and portability, and its low cost means that it could be used as an auxiliary tool in the diagnosis of neuritis and its treatment, especially in basic health units.
Topics: Humans; Leprosy; Neural Conduction; Neuralgia; Neuritis; Ulnar Nerve; Ulnar Neuropathies; Ultrasonography
PubMed: 35486667
DOI: 10.1371/journal.pntd.0010393