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Clinical Neurophysiology : Official... Jul 2024One hundred years ago, Erlanger and Gasser demonstrated that conduction velocity is correlated with the diameter of a peripheral nerve axon. Later, they also... (Review)
Review
One hundred years ago, Erlanger and Gasser demonstrated that conduction velocity is correlated with the diameter of a peripheral nerve axon. Later, they also demonstrated that the functional role of the axon is related to its diameter: touch is signalled by large-diameter axons, whereas pain and temperature are signalled by small-diameter axons. Certain discoveries in recent decades prompt a modification of this canonical classification. Here, we review the evidence for unmyelinated (C) fibres signalling touch at a slow conduction velocity and likely contributing to affective aspects of tactile information. We also review the evidence for large-diameter Aβ afferents signalling pain at ultrafast conduction velocity and likely contributing to the rapid nociceptive withdrawal reflex. These discoveries imply that conduction velocity is not as clear-cut an indication of the functional role of the axon as previously thought. We finally suggest that a future taxonomy of the peripheral afferent nervous system might be based on the combination of the axońs molecular expression and electrophysiological response properties.
Topics: Humans; Animals; Peripheral Nerves; Neural Conduction; Touch; Pain; Nerve Fibers, Unmyelinated; Axons
PubMed: 38704307
DOI: 10.1016/j.clinph.2024.04.008 -
Experimental Neurology Aug 2022Neurons of the peripheral nervous system retain the intrinsic capability of regenerate their axons after injury, by triggering a complex activation response. This... (Review)
Review
Neurons of the peripheral nervous system retain the intrinsic capability of regenerate their axons after injury, by triggering a complex activation response. This genetic switch is dependent of signals from the injured axon. Schwann cells (SCs) in the distal stump of an injured nerve also play an active role in the local regulation of axonal programs, by using cell-to-cell contacts but also secreted signals, the so-called secretome. Secretome contains all the proteins (cytokines, growth factors and others) secreted by the cell and includes extracellular vesicles. The released vesicles can transport signaling proteins and both coding and regulatory RNAs, thus facilitating multilevel communication. It is nowadays clear that secretome of SCs is fundamental to both orchestrate Wallerian degeneration and to sustain axonal regeneration. Therefore, the use of secretome has emerged as an alternative to cell therapy in the field of tissue regeneration. In fact, separate components of SC secretome have been extensively used in experimental models to enhance peripheral nerve regeneration after injury. However, the most used secretome in neural therapies has been the one derived from mesenchymal (MSC) or other derived stem cells. In fact, the effects of cell therapy with MSCs have been mainly associated with the secretion of bioactive molecules and extracellular vesicles, which constitute their secretome. In this review, we first describe the role of SC and macrophage secretomes on Wallerian degeneration and axonal regeneration after peripheral nerve injury. Then, we review the different works reported in the literature that have used secretomes of SCs or MSCs in the treatment of peripheral nerve injuries in experimental models, to highlight the use of secretomes as a promising cell-free therapeutic approach, that reduces some of the risks associated with the use of cells, such as tumor formation or rejection.
Topics: Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells; Secretome; Wallerian Degeneration
PubMed: 35398149
DOI: 10.1016/j.expneurol.2022.114069 -
International Journal of Molecular... Jan 2023Regeneration of damaged peripheral nerves remains one of the main challenges of neurosurgery and regenerative medicine, a nerve functionality is rarely restored,... (Review)
Review
Regeneration of damaged peripheral nerves remains one of the main challenges of neurosurgery and regenerative medicine, a nerve functionality is rarely restored, especially after severe injuries. Researchers are constantly looking for innovative strategies for tackling this problem, with the development of advanced tissue-engineered nerve conduits and new pharmacological and physical interventions, with the aim of improving patients' life quality. Different evaluation methods can be used to study the effectiveness of a new treatment, including functional tests, morphological assessment of regenerated nerve fibers and biomolecular analyses of key factors necessary for good regeneration. The number and diversity of protocols and methods, as well as the availability of innovative technologies which are used to assess nerve regeneration after experimental interventions, often makes it difficult to compare results obtained in different labs. The purpose of the current review is to describe the main morphological approaches used to evaluate the degree of nerve fiber regeneration in terms of their usefulness and limitations.
Topics: Humans; Peripheral Nerve Injuries; Peripheral Nerves; Nerve Fibers; Tissue Engineering; Nerve Regeneration; Sciatic Nerve
PubMed: 36768142
DOI: 10.3390/ijms24031818 -
Pharmacology & Therapeutics Jun 2011In addition to using glutamate as a neurotransmitter at central synapses, many primary sensory neurons release glutamate from peripheral terminals. Primary sensory... (Review)
Review
In addition to using glutamate as a neurotransmitter at central synapses, many primary sensory neurons release glutamate from peripheral terminals. Primary sensory neurons with cell bodies in dorsal root or trigeminal ganglia produce glutaminase, the synthetic enzyme for glutamate, and transport the enzyme in mitochondria to peripheral terminals. Vesicular glutamate transporters fill neurotransmitter vesicles with glutamate and they are shipped to peripheral terminals. Intense noxious stimuli or tissue damage causes glutamate to be released from peripheral afferent nerve terminals and augmented release occurs during acute and chronic inflammation. The site of action for glutamate can be at the autologous or nearby nerve terminals. Peripheral nerve terminals contain both ionotropic and metabotropic excitatory amino acid receptors (EAARs) and activation of these receptors can lower the activation threshold and increase the excitability of primary afferents. Antagonism of EAARs can reduce excitability of activated afferents and produce antinociception in many animal models of acute and chronic pain. Glutamate injected into human skin and muscle causes acute pain. Trauma in humans, such as arthritis, myalgia, and tendonitis, elevates glutamate levels in affected tissues. There is evidence that EAAR antagonism at peripheral sites can provide relief in some chronic pain sufferers.
Topics: Afferent Pathways; Animals; Glutamic Acid; Humans; Pain; Peripheral Nerves; Receptors, Glutamate; Synaptic Transmission
PubMed: 21276816
DOI: 10.1016/j.pharmthera.2011.01.005 -
Nature Communications Aug 2020The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and...
The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying peripheral interfacing technologies. Here, we present a microscale implantable device - the nanoclip - for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high signal-to-noise ratio recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation within the confines of the small device can achieve multi-dimensional control of a small nerve. These results highlight the potential of new microscale design and fabrication techniques for realizing viable devices for long-term peripheral interfacing.
Topics: Animals; Biomedical Engineering; Electrodes, Implanted; Evoked Potentials; Finches; Male; Microelectrodes; Microtechnology; Models, Animal; Peripheral Nerves; Printing, Three-Dimensional; Signal-To-Noise Ratio
PubMed: 32826892
DOI: 10.1038/s41467-020-18032-4 -
European Journal of Physical and... Dec 2012Although the combination of a detailed physical examination and a subsequent electrodiagnostic study is used for the diagnosis of peripheral nerve disorders, prompt... (Review)
Review
Although the combination of a detailed physical examination and a subsequent electrodiagnostic study is used for the diagnosis of peripheral nerve disorders, prompt imaging may also be necessary in daily practice. In this regard, as having higher spatial resolution, and being a faster, more cost-effective and dynamic study; ultrasound (US) has become a very convenient first-line imaging modality for the diagnosis, follow-up and treatment (i.e. guiding interventions or planning for surgery) of peripheral nerve pathologies. Yet, using the probe of US to "sono-auscultate" the peripheral nerves is indisputably paramount for unmasking the whole scenario of injury. Likewise, in this review, we will try to exemplify the role of US for the diagnosis and follow-up of peripheral nerve disorders in clinical practice.
Topics: Cost-Benefit Analysis; Humans; Nerve Compression Syndromes; Peripheral Nerve Injuries; Peripheral Nerves; Peripheral Nervous System Diseases; Peripheral Nervous System Neoplasms; Ultrasonography, Interventional
PubMed: 23183452
DOI: No ID Found -
Orphanet Journal of Rare Diseases May 2024To investigate the peripheral nervous system involvement in sialidosis with typical features of myoclonus, seizure, and giant waves in somatosensory evoked potentials...
BACKGROUND
To investigate the peripheral nervous system involvement in sialidosis with typical features of myoclonus, seizure, and giant waves in somatosensory evoked potentials suggesting hyperexcitability in the central nervous system.
METHODS
The clinical presentation of patients with genetically confirmed sialidosis was recorded. Neurophysiological studies, including nerve conduction studies (NCSs), F-wave studies, and needle electromyography (EMG), were performed on these patients.
RESULTS
Six patients (M/F: 2:4) were recruited. In addition to the classical presentation, intermittent painful paresthesia was noted in four patients, and three of whom reported it as the earliest symptom. In the NCSs, one patient had reduced compound muscle action potential amplitudes in the right ulnar nerve, while another patient had prolonged distal motor latency in the bilateral tibial and peroneal nerves. Prolonged F-wave latency (83.3%), repeater F-waves (50%), and neurogenic polyphasic waves in EMG (in 2 out of 3 examined patients) were also noted. Interestingly, a very late response was noted in the F-wave study of all patients, probably indicating lesions involving the proximal peripheral nerve or spinal cord.
CONCLUSION
In addition to the central nervous system, the peripheral nervous system is also involved in sialidosis, with corresponding clinical symptoms. Further study on these phenomena is indicated.
Topics: Humans; Male; Female; Adult; Mucolipidoses; Electromyography; Neural Conduction; Young Adult; Peripheral Nerves; Adolescent; Peripheral Nervous System; Evoked Potentials, Somatosensory; Middle Aged; Child
PubMed: 38790028
DOI: 10.1186/s13023-024-03216-8 -
Advanced Science (Weinheim,... Apr 2022The treatment of peripheral nerve defects has always been one of the most challenging clinical practices in neurosurgery. Currently, nerve autograft is the preferred... (Review)
Review
The treatment of peripheral nerve defects has always been one of the most challenging clinical practices in neurosurgery. Currently, nerve autograft is the preferred treatment modality for peripheral nerve defects, while the therapy is constantly plagued by the limited donor, loss of donor function, formation of neuroma, nerve distortion or dislocation, and nerve diameter mismatch. To address these clinical issues, the emerged nerve guide conduits (NGCs) are expected to offer effective platforms to repair peripheral nerve defects, especially those with large or complex topological structures. Up to now, numerous technologies are developed for preparing diverse NGCs, such as solvent casting, gas foaming, phase separation, freeze-drying, melt molding, electrospinning, and three-dimensional (3D) printing. 3D printing shows great potential and advantages because it can quickly and accurately manufacture the required NGCs from various natural and synthetic materials. This review introduces the application of personalized 3D printed NGCs for the precision repair of peripheral nerve defects and predicts their future directions.
Topics: Nerve Regeneration; Peripheral Nerves; Printing, Three-Dimensional; Tissue Scaffolds
PubMed: 35182046
DOI: 10.1002/advs.202103875 -
Environmental Health Perspectives Oct 1978Neurotoxic substances affect the nervous system in a selective manner. One possible basis for this selectivity is blood vessel permeability. In general, the central... (Review)
Review
Neurotoxic substances affect the nervous system in a selective manner. One possible basis for this selectivity is blood vessel permeability. In general, the central nervous system and the peripheral nerve trunks have impermeable blood vessels, but in certain parts the capillaries are "leaky," allowing the passage of a plasma filtrate. Intravenously injected protein tracers rapidly reach nerve cells in these regions, with the implication that these nerve cells are also readily accessible to circulating neurotoxic substances. Some examples of neurotoxicity in the central nervous system show a selectivity that could be due to capillary permeability. In experimental methylmercury poisoning, cranial nerve V and sensory dorsal root ganglia, which lie in regions of vascular permeability, are particularly susceptible. A number of drug and chemically induced neuropathies are predominantly sensory, and may be due, directly or indirectly, to the accessibility of neurotoxic substances to sensory neurons. Examination of areas of potential vulnerability to circulating toxic substances may be of value in the experimental testing of substances for neurotoxicity, where pharmacological tests may be negative and clinical symptoms difficult to assess.
Topics: Animals; Blood-Brain Barrier; Brain; Capillary Permeability; Central Nervous System; Humans; Nerve Degeneration; Nervous System; Nervous System Diseases; Neurons; Peripheral Nerves
PubMed: 363411
DOI: 10.1289/ehp.7826107 -
Neurotherapeutics : the Journal of the... Apr 2010Nerve blocks and neurostimulation are reasonable therapeutic options in patients with head and neck neuralgias. In addition, these peripheral nerve procedures can also... (Review)
Review
Nerve blocks and neurostimulation are reasonable therapeutic options in patients with head and neck neuralgias. In addition, these peripheral nerve procedures can also be effective in primary headache disorders, such as migraine and cluster headaches. Nerve blocks for headaches are generally accomplished by using small subcutaneous injections of amide-type local anesthetics, such as lidocaine and bupivicaine. Targets include the greater occipital nerve, lesser occipital nerve, auriculotemporal nerve, supratrochlear and supraorbital nerves, sphenopalatine ganglion, cervical spinal roots, and facet joints of the upper cervical spine. Although definitive studies examining the usefulness of nerve blocks are lacking, reports suggest that this area deserves further attention in the hope of acquiring evidence of effectiveness.
Topics: Anesthetics, Local; Bupivacaine; Electric Stimulation; Headache; Humans; Lidocaine; Nerve Block; Peripheral Nerves
PubMed: 20430319
DOI: 10.1016/j.nurt.2010.03.001