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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 -
Current Opinion in Neurology Oct 2021This review focuses on the current insights and developments in neuralgic amyotrophy (NA), an auto-immune multifocal peripheral nervous system disorder that leaves many... (Review)
Review
PURPOSE OF REVIEW
This review focuses on the current insights and developments in neuralgic amyotrophy (NA), an auto-immune multifocal peripheral nervous system disorder that leaves many patients permanently impaired if not recognized and treated properly.
RECENT FINDINGS
NA is not as rare as previously thought. The phenotype is broad, and recent nerve imaging developments suggest that NA is the most common cause of acute anterior or posterior interosseous nerve palsy. Phrenic nerve involvement occurs in 8% of all NA patients, often with debilitating consequences. Acute phase treatment of NA with steroids or i.v. immunoglobulin may benefit patients. Long-term consequences are the rule, and persisting symptoms are mainly caused by a combination of decreased endurance in the affected nerves and an altered posture and movement pattern, not by the axonal damage itself. Patients benefit from specific rehabilitation treatment. For nerves that do not recover, surgery may be an option.
SUMMARY
NA is not uncommon, and has a long-term impact on patients' well-being. Early immunomodulating treatment, and identifying phrenic neuropathy or complete nerve paralysis is important for optimal recovery. For persistent symptoms a specific treatment strategy aiming at regaining an energy balance and well-coordinated scapular movement are paramount.
Topics: Brachial Plexus Neuritis; Humans; Paralysis; Peripheral Nervous System Diseases
PubMed: 34054111
DOI: 10.1097/WCO.0000000000000968 -
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 -
Journal of Neurology, Neurosurgery, and... Aug 2020Neuralgic amyotrophy (NA), also known as Parsonage-Turner syndrome, is characterised by sudden pain attacks, followed by patchy muscle paresis in the upper extremity.... (Review)
Review
Neuralgic amyotrophy (NA), also known as Parsonage-Turner syndrome, is characterised by sudden pain attacks, followed by patchy muscle paresis in the upper extremity. Recent reports have shown that incidence is much higher than previously assumed and that the majority of patients never achieve full recovery. Traditionally, the diagnosis was mainly based on clinical observations and treatment options were confined to application of corticosteroids and symptomatic management, without proven positive effects on long-term outcomes. These views, however, have been challenged in the last years. Improved imaging methods in MRI and high-resolution ultrasound have led to the identification of structural peripheral nerve pathologies in NA, most notably hourglass-like constrictions. These pathognomonic findings have paved the way for more accurate diagnosis through high-resolution imaging. Furthermore, surgery has shown to improve clinical outcomes in such cases, indicating the viability of peripheral nerve surgery as a valuable treatment option in NA. In this review, we present an update on the current knowledge on this disease, including pathophysiology and clinical presentation, moving on to diagnostic and treatment paradigms with a focus on recent radiological findings and surgical reports. Finally, we present a surgical treatment algorithm to support clinical decision making, with the aim to encourage translation into day-to-day practice.
Topics: Brachial Plexus Neuritis; Diagnosis, Differential; Humans; Peripheral Nerves
PubMed: 32487526
DOI: 10.1136/jnnp-2020-323164 -
Muscle & Nerve Mar 2016In this review we provide a current overview of the clinical features, pathophysiology, epidemiology, and diagnostic and therapeutic strategies in neuralgic amyotrophy... (Review)
Review
In this review we provide a current overview of the clinical features, pathophysiology, epidemiology, and diagnostic and therapeutic strategies in neuralgic amyotrophy (NA). The disorder has several phenotypic variations, with a classic form in 70% of the patients. It is not rare, with an incidence of 1 per 1,000 individuals, but it is still often missed. Recurrences are common, yet the proposed multifactorial etiology, which includes genetic, biomechanical, and immunologic factors, limits our capacity to predict or prevent them. NA is a clinical diagnosis, and ancillary studies serve to exclude infectious or malignant causes or to assess a differential diagnosis. If patients are seen early and are still in pain, a short trial of high-dose oral corticosteroids is advised, and adequate analgesia may require opioids and non-steroidal anti-inflammatory drugs. Persistent complaints are common, and a multidisciplinary rehabilitation approach focusing on scapular coordination, energy distribution strategies, and self-management is indicated.
Topics: Brachial Plexus Neuritis; Diagnosis, Differential; Disease Management; Humans
PubMed: 26662794
DOI: 10.1002/mus.25008 -
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 -
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 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2022A review of the literature covering the issues of etiology, pathogenesis, variety of atypical forms, diagnosis and management of patients with neuralgic amyotrophy is... (Review)
Review
A review of the literature covering the issues of etiology, pathogenesis, variety of atypical forms, diagnosis and management of patients with neuralgic amyotrophy is presented.
Topics: Brachial Plexus Neuritis; Humans
PubMed: 35175697
DOI: 10.17116/jnevro20221220118 -
Muscle & Nerve Nov 2023Myelin-associated glycoprotein (MAG) is a transmembrane glycoprotein concentrated in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths that serves... (Review)
Review
Myelin-associated glycoprotein (MAG) is a transmembrane glycoprotein concentrated in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths that serves as an antigen for immunoglobulin M (IgM) monoclonal antibodies. Individuals who harbor anti-MAG antibodies classically develop a progressive autoimmune peripheral neuropathy characterized clinically by ataxia, distal sensory loss, and gait instability, and electrophysiologically by distally accentuated conduction velocity slowing. Although off-label immunotherapy is common, there are currently no proven effective disease-modifying therapeutics, and most patients experience slow accumulation of disability over years and decades. The typically slowly progressive nature of this neuropathy presents unique challenges when trying to find effective anti-MAG therapeutic agents. Drug development has also been hampered by the lack of validated outcome measures that can detect clinically meaningful changes in a reasonable amount of time as well as by the lack of disease activity biomarkers. In this invited review, we provide an update on the state of clinicometric outcome measures and disease activity biomarkers in anti-MAG neuropathy. We highlight the insensitivity of widely used existing clinicometric outcome measures such as the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score as well as the INCAT sensory subscore in anti-MAG neuropathy, referencing the two previous negative randomized controlled clinical trials evaluating rituximab. We then discuss newly emerging candidate therapeutic agents, including tyrosine kinase inhibitors and enhanced B-cell-depleting agents, among others. We conclude with a practical approach to the evaluation and management of anti-MAG neuropathy patients.
Topics: Humans; Myelin-Associated Glycoprotein; Peripheral Nervous System Diseases; Rituximab; Antibodies, Monoclonal; Immunoglobulin M; Autoantibodies; Neuritis; Biomarkers
PubMed: 37602932
DOI: 10.1002/mus.27954 -
Dental Clinics of North America Oct 2018Neuropathic pain of the orofacial region can cause much distress in individuals presenting with this condition. It may be easily mistaken for dental pain, and hence many... (Review)
Review
Neuropathic pain of the orofacial region can cause much distress in individuals presenting with this condition. It may be easily mistaken for dental pain, and hence many individuals may undergo unnecessary dental work. Knowledge of the types of neuropathic orofacial pain may assist in timely diagnosis and improvement of a patient's quality of life.
Topics: Facial Nerve; Facial Pain; Glossopharyngeal Nerve Diseases; Herpes Zoster; Humans; Laryngeal Nerves; Neuralgia; Neuralgia, Postherpetic; Neuritis; Nociception; Trigeminal Neuralgia
PubMed: 30189983
DOI: 10.1016/j.cden.2018.05.005