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Concept: Peripheral nervous system


Postherpetic neuralgia (PHN) is a particularly challenging neuropathic pain condition, especially when it involves the trigeminal nerve. Peripheral nerve stimulation (PNS) can provide 50-70% improvement in pain to many who fail medical management. However, this pain relief can be incomplete, and residual pain may persist for many years. Here we report a case that was successfully managed by a novel technique of combining supraorbital nerve stimulation with botulinum toxin type A (BTA) for intractable ophthalmic PHN.

Concepts: Neurology, Pain, Botulinum toxin, Postherpetic neuralgia, Peripheral nervous system, Trigeminal nerve, Trigeminal neuralgia, Ophthalmic nerve


Myocarditis, which is caused by viral infection, can lead to heart failure, malignant arrhythmias, and even sudden cardiac death in young patients. It is also one of the most important causes of dilated cardiomyopathy worldwide. Although remarkable advances in diagnosis and understanding of pathophysiological mechanisms of viral myocarditis have been gained during recent years, no standard treatment strategies have been defined as yet. Fortunately, recent studies present some evidence that immunomodulating therapy is effective for myocarditis. The immunomodulatory effect of the autonomic nervous system has raised considerable interest over recent decades. Studying the influence on the inflammation and immune system of the sympathetic and parasympathetic nervous systems will not only increase our understanding of the mechanism of disease but could also lead to the identification of potential new therapies for viral myocarditis. Studies have shown that the immunomodulating effect of the sympathetic and parasympathetic nervous system is realized by the release of neurotransmitters to their corresponding receptors (catecholamine for α or β adrenergic receptor, acetylcholine for α7 nicotinic acetylcholinergic receptor). This review will discuss the current knowledge of the roles of both the sympathetic and parasympathetic nervous system in inflammation, with a special focus on their roles in viral myocarditis.

Concepts: Nervous system, Neurotransmitter, Acetylcholine, Autonomic nervous system, Sympathetic nervous system, Parasympathetic nervous system, Peripheral nervous system, Enteric nervous system


Leprosy is an endemic infectious disease caused by Mycobacterium leprae that predominantly attacks the skin and peripheral nerves, leading to progressive impairment of motor, sensory and autonomic function. Little is known about how this peripheral neuropathy affects corticospinal excitability of handgrip muscles. Our purpose was to explore the motor cortex organization after progressive peripheral nerve injury and upper-limb dysfunction induced by leprosy using noninvasive transcranial magnetic stimulation (TMS).

Concepts: Infectious disease, Acetylcholine, Autonomic nervous system, Transcranial magnetic stimulation, Parasympathetic nervous system, Peripheral nervous system, Leprosy, Mycobacterium leprae


Although the gastrointestinal (GI) tract contains intrinsic neural plexuses that allow a significant degree of independent control over GI functions, the central nervous system provides extrinsic neural inputs that modulate, regulate and integrate these functions. In particular, the vagus nerve (VN) provides the parasympathetic innervation to the GI tract, co-ordinates the complex interactions between central and peripheral neural control mechanisms. This review will discuss the physiological roles of the afferent (sensory) and motor (efferent) vagus in regulation of appetite, mood and the immune system, as well as the pathophysiological outcomes of VN dysfunction resulting in obesity, mood disorders and inflammation. The therapeutic potential of VN modulation to attenuate or reverse these pathophysiological outcomes and restore autonomic homeostasis will also be discussed.

Concepts: Immune system, Central nervous system, Nervous system, Brain, Systems theory, Axon, Nerve, Peripheral nervous system


Peripheral nerve injury causes neuropathic pain accompanied by remarkable microgliosis in the spinal cord dorsal horn. However, it is still debated whether infiltrated monocytes contribute to injury-induced expansion of the microglial population. Here, we found that spinal microgliosis predominantly results from local proliferation of resident microglia but not from infiltrating monocytes after spinal nerve transection (SNT) by using two genetic mouse models (CCR2(RFP/+):CX3CR1(GFP/+) and CX3CR1(creER/+):R26(tdTomato/+) mice) as well as specific staining of microglia and macrophages. Pharmacological inhibition of SNT-induced microglial proliferation correlated with attenuated neuropathic pain hypersensitivities. Microglial proliferation is partially controlled by purinergic and fractalkine signaling, as CX3CR1(-/-) and P2Y12(-/-) mice show reduced spinal microglial proliferation and neuropathic pain. These results suggest that local microglial proliferation is the sole source of spinal microgliosis, which represents a potential therapeutic target for neuropathic pain management.

Concepts: Immune system, Nervous system, Hypersensitivity, Pain, Microglia, Spinal nerve, Peripheral nervous system


Injuries to the peripheral nervous system are major sources of disability and often result in painful neuropathies or the impairment of muscle movement and/or normal sensations. For gaps smaller than 10 mm in rodents, nearly normal functional recovery can be achieved; for longer gaps, however, there are challenges that have remained insurmountable. The current clinical gold standard used to bridge long, nonhealing nerve gaps, the autologous nerve graft (autograft), has several drawbacks. Despite best efforts, engineering an alternative “nerve bridge” for peripheral nerve repair remains elusive; hence, there is a compelling need to design new approaches that match or exceed the performance of autografts across critically sized nerve gaps. Here an immunomodulatory approach to stimulating nerve repair in a nerve-guidance scaffold was used to explore the regenerative effect of reparative monocyte recruitment. Early modulation of the immune environment at the injury site via fractalkine delivery resulted in a dramatic increase in regeneration as evident from histological and electrophysiological analyses. This study suggests that biasing the infiltrating inflammatory/immune cellular milieu after injury toward a proregenerative population creates a permissive environment for repair. This approach is a shift from the current modes of clinical and laboratory methods for nerve repair, which potentially opens an alternative paradigm to stimulate endogenous peripheral nerve repair.

Concepts: Central nervous system, Nervous system, Critical thinking, Action potential, Nerve, Spinal nerve, Peripheral nervous system, Somatic nervous system


The blood-nerve barrier (BNB), formed by tight junction-forming microvessels within peripheral nerve endoneurium, exists to regulate its internal microenvironment essential for effective axonal signal transduction. Relatively little is known about the unique human BNB molecular composition. Such knowledge is crucial to comprehend the relationships between the systemic circulation and peripheral nerves in health, adaptations to intrinsic or extrinsic perturbations and alterations that may result in disease. We performed RNA-sequencing on cultured early- and late-passage adult primary human endoneurial endothelial cells and laser-capture microdissected endoneurial microvessels from four cryopreserved normal adult human sural nerves referenced to the Genome Reference Consortium Human Reference 37 genome browser, using predefined criteria guided by known transcript or protein expression in vitro and in situ. We identified 12881 common transcripts associated by 125 independent biological networks, defined as the normal adult BNB transcriptome, including a comprehensive array of transporters and specialized intercellular junctional complex components. These identified transcripts and their interacting networks provide insights into peripheral nerve microvascular morphogenesis, restrictive barrier formation, influx and efflux transporters with relevance to understanding peripheral nerve homeostasis and pharmacology, including targeted drug delivery and the mediators of leukocyte trafficking in peripheral nerves during normal immunosurveillance.

Concepts: Organism, Heart, Action potential, Axon, In vitro, Nerve, Spinal nerve, Peripheral nervous system


Pathological studies on Parkinson’s disease (PD) patients suggest that PD pathology progresses from the enteric nervous system (ENS) and the olfactory bulb into the central nervous system. We have previously shown that environmental toxins acting locally on the ENS mimic this PD-like pathology progression pattern in mice. Here, we show for the first time that the resection of the autonomic nerves stops this progression. Moreover, our results show that an environmental toxin (i.e. rotenone) promotes the release of alpha-synuclein by enteric neurons and that released enteric alpha-synuclein is up-taken by presynaptic sympathetic neurites and retrogradely transported to the soma, where it accumulates. These results strongly suggest that pesticides can initiate the progression of PD pathology and that this progression is based on the transneuronal and retrograde axonal transport of alpha-synuclein. If confirmed in patients, this study would have crucial implications in the strategies used to prevent and treat PD.

Concepts: Nervous system, Neuron, Brain, Axon, Synapse, Autonomic nervous system, Parasympathetic nervous system, Peripheral nervous system


Integrins are cell surface receptors that form the link between extracellular matrix molecules of the cell environment and internal cell signalling and the cytoskeleton. They are involved in several processes, e.g. adhesion and migration during development and repair. This review focuses on the role of integrins in axonal regeneration. Integrins participate in spontaneous axonal regeneration in the peripheral nervous system through binding to various ligands that either inhibit or enhance their activation and signalling. Integrin biology is more complex in the central nervous system. Integrins receptors are transported into growing axons during development, but selective polarised transport of integrins limits the regenerative response in adult neurons. Manipulation of integrins and related molecules to control their activation state and localisation within axons is a promising route towards stimulating effective regeneration in the central nervous system.

Concepts: Central nervous system, Nervous system, Neuron, Brain, Signal transduction, Extracellular matrix, Axon, Peripheral nervous system


Irritable bowel syndrome is one of the most common gastrointestinal disorders in developed nations. It is characterized by abdominal pain, altered bowel habits, and bloating. Several non-pharmacological and pharmacological agents, which target the peripheral gastrointestinal system and central nervous system, are used to treat the syndrome. The individual and societal impact of investigating and managing the syndrome is substantial, and despite newer treatments, many patients have unmet needs. Intense research at many international sites has improved the understanding of pathophysiology of the syndrome, but developing treatments that are effective, safe, and that have tolerable side effects remains a challenge. This review briefly summarizes the currently available treatments for irritable bowel syndrome then focuses on newer non-pharmacological and pharmacological therapies and recent evidence for older treatments. Recent guidelines on the treatment of irritable bowel syndrome are also discussed.

Concepts: Central nervous system, Nervous system, Brain, Abdominal pain, Gastroenterology, Irritable bowel syndrome, Abdomen, Peripheral nervous system