The development of central nociceptive processing and descending modulation of pain

Author(s):  
Maria Fitzgerald

Newborn mammals display robust responses to noxious or tissue-damaging stimulation. These nociceptive or “pain” responses arise from neural activity at different levels of the central nervous system. Protective reflex movements and physiological reactions mediated by spinal cord and brainstem circuits are essential for the preservation of life and well-being but should not be equated with pain awareness. The unique sensation of pain and its unpleasant, threatening quality requires activity in the cortical and subcortical regions of the brain. These brain regions also have the potential to actively increase or decrease pain experience by exerting top-down control of spinal cord and brainstem nociceptive circuits. This chapter summarizes our current knowledge of the development of central nociceptive pathways in the young mammalian brain and the postnatal maturation of top-down pain control. It aims to provide a scientific, mechanistic understanding of infant and childhood pain experience, and their ability to cope with painful events.

1996 ◽  
Vol 76 (2) ◽  
pp. 319-370 ◽  
Author(s):  
M. E. Schwab ◽  
D. Bartholdi

For many decades, the inability of lesioned central neurons to regrow was accepted almost as a "law of nature", and on the clinical level, spinal cord and brain lesions were seen as being irreversible. Today we are starting to understand the mechanisms of neuronal regeneration in the central nervous system and its presence in the periphery. There is now a rapid expansion in this field of neuroscience. Developmental neurobiology has produced tools and concepts that start to show their impact on regeneration research. This is particularly true for the availability of antibodies and factors and for the rapidly growing cellular and molecular understanding of crucial aspects of neurite growth, guidance, target finding, and synapse stabilization. New cell biological concepts on the mechanisms of neuron survival and death and on the interaction of inflammatory cells with the central nervous system also find their way into the field of spinal cord and brain lesions and have, indeed, led already to new therapeutic approaches. This review briefly summarizes the current knowledge on the mechanisms involved in degeneration and tissue loss and in axonal regeneration subsequent to spinal cord lesions, particularly in mammals and humans.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 183
Author(s):  
Elvira Brattico ◽  
Leonardo Bonetti ◽  
Gabriella Ferretti ◽  
Peter Vuust ◽  
Carmela Matrone

Motor exercise, such as sport or musical activities, helps with a plethora of diseases by modulating brain functions in neocortical and subcortical regions, resulting in behavioural changes related to mood regulation, well-being, memory, and even cognitive preservation in aging and neurodegenerative diseases. Although evidence is accumulating on the systemic neural mechanisms mediating these brain effects, the specific mechanisms by which exercise acts upon the cellular level are still under investigation. This is particularly the case for music training, a much less studied instance of motor exercise than sport. With regards to sport, consistent neurobiological research has focused on the brain-derived neurotrophic factor (BDNF), an essential player in the central nervous system. BDNF stimulates the growth and differentiation of neurons and synapses. It thrives in the hippocampus, the cortex, and the basal forebrain, which are the areas vital for memory, learning, and higher cognitive functions. Animal models and neurocognitive experiments on human athletes converge in demonstrating that physical exercise reliably boosts BDNF levels. In this review, we highlight comparable early findings obtained with animal models and elderly humans exposed to musical stimulation, showing how perceptual exposure to music might affect BDNF release, similar to what has been observed for sport. We subsequently propose a novel hypothesis that relates the neuroplastic changes in the human brains after musical training to genetically- and exercise-driven BDNF levels.


2018 ◽  
Vol 92 (18) ◽  
Author(s):  
Jacob I. Ayers ◽  
Cara J. Riffe ◽  
Zachary A. Sorrentino ◽  
Jeffrey Diamond ◽  
Eric Fagerli ◽  
...  

ABSTRACTMisfolded alpha-synuclein (αS) may exhibit a number of characteristics similar to those of the prion protein, including the apparent ability to spread along neuroanatomical connections. The demonstration for this mechanism of spread is largely based on the intracerebral injections of preaggregated αS seeds in mice, in which it cannot be excluded that diffuse, surgical perturbations and hematogenous spread also contribute to the propagation of pathology. For this reason, we have utilized the sciatic nerve as a route of injection to force the inoculum into the lumbar spinal cord and induce a localized site for the onset of αS inclusion pathology. Our results demonstrate that mouse αS fibrils (fibs) injected unilaterally in the sciatic nerve are efficient in inducing pathology and the onset of paralytic symptoms in both the M83 and M20 lines of αS transgenic mice. In addition, a spatiotemporal study of these injections revealed a predictable spread of pathology to brain regions whose axons synapse directly on ventral motor neurons in the spinal cord, strongly supporting axonal transport as a mechanism of spread of the αS inducing, or seeding, factor. We also revealed a relatively decreased efficiency for human αS fibs containing the E46K mutation to induce disease via this injection paradigm, supportive of recent studies demonstrating a diminished ability of this mutant αS to undergo aggregate induction. These results further demonstrate prion-like properties for αS by the ability for a progression and spread of αS inclusion pathology along neuroanatomical connections.IMPORTANCEThe accumulation of alpha-synuclein (αS) inclusions is a hallmark feature of Parkinson's disease (PD) and PD-related diseases. Recently, a number of studies have demonstrated similarities between the prion protein and αS, including its ability to spread along neuroanatomical tracts throughout the central nervous system (CNS). However, there are caveats in each of these studies in which the injection routes used had the potential to result in a widespread dissemination of the αS-containing inocula, making it difficult to precisely define the mechanisms of spread. In this study, we assessed the spread of pathology following a localized induction of αS inclusions in the lumbar spinal cord following a unilateral injection in the sciatic nerve. Using this paradigm, we demonstrated the ability for αS inclusion spread and/or induction along neuroanatomical tracts within the CNS of two αS-overexpressing mouse models.


2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.


2020 ◽  
Vol 25 (3) ◽  
pp. 162-173 ◽  
Author(s):  
Sascha Zuber ◽  
Matthias Kliegel

Abstract. Prospective Memory (PM; i.e., the ability to remember to perform planned tasks) represents a key proxy of healthy aging, as it relates to older adults’ everyday functioning, autonomy, and personal well-being. The current review illustrates how PM performance develops across the lifespan and how multiple cognitive and non-cognitive factors influence this trajectory. Further, a new, integrative framework is presented, detailing how those processes interplay in retrieving and executing delayed intentions. Specifically, while most previous models have focused on memory processes, the present model focuses on the role of executive functioning in PM and its development across the lifespan. Finally, a practical outlook is presented, suggesting how the current knowledge can be applied in geriatrics and geropsychology to promote healthy aging by maintaining prospective abilities in the elderly.


2013 ◽  
Vol 41 (01) ◽  
pp. 63-66
Author(s):  
D. Schaudien ◽  
C. Flieshardt ◽  
I. Moser ◽  
H. Hotzel ◽  
A. Tipold ◽  
...  

SummaryGranulomatous myelitis due to infection with Mycobacterium avium was diagnosed in a 4-year-old male neutered European mink (Mustela lutreola). The causative agent was detected by an acid-fast stain and further characterized by polymerase chain reaction and DNA sequencing of the PCR product. A thorough histological evaluation of the remaining organs revealed no granulomatous lesions or detectable acid-fast organisms. Although minks are generally highly susceptible for mycobacteria, localised infections, especially of the central nervous system, are unusual and may represent an atypical chronic form of the disease.


1963 ◽  
Vol 44 (3) ◽  
pp. 475-480 ◽  
Author(s):  
R. Grinberg

ABSTRACT Radiologically thyroidectomized female Swiss mice were injected intraperitoneally with 131I-labeled thyroxine (T4*), and were studied at time intervals of 30 minutes and 4, 28, 48 and 72 hours after injection, 10 mice for each time interval. The organs of the central nervous system and the pituitary glands were chromatographed, and likewise serum from the same animal. The chromatographic studies revealed a compound with the same mobility as 131I-labeled triiodothyronine in the organs of the CNS and in the pituitary gland, but this compound was not present in the serum. In most of the chromatographic studies, the peaks for I, T4 and T3 coincided with those for the standards. In several instances, however, such an exact coincidence was lacking. A tentative explanation for the presence of T3* in the pituitary gland following the injection of T4* is a deiodinating system in the pituitary gland or else the capacity of the pituitary gland to concentrate T3* formed in other organs. The presence of T3* is apparently a characteristic of most of the CNS (brain, midbrain, medulla and spinal cord); but in the case of the optic nerve, the compound is not present under the conditions of this study.


1985 ◽  
Vol 55 ◽  
Author(s):  
F. Terry Hambrecht

ABSTRACTNeural prostheses which are commercially available include cochlear implants for treating certain forms of deafness and urinary bladder evacuation prostheses for individuals with spinal cord disorders. In the future we can anticipate improvements in bioelectrodes and biomaterials which should permit more sophisticated devices such as visual prostheses for the blind and auditory prostheses for the deaf based on microstimulation of the central nervous system.


Author(s):  
John K. Yue ◽  
Rachel E. Tsolinas ◽  
John F. Burke ◽  
Hansen Deng ◽  
Pavan S. Upadhyayula ◽  
...  

Author(s):  
Semeleva E.V. ◽  
Blinova E.V. ◽  
Zaborovsky A.V. ◽  
Vasilkina O.V. ◽  
Shukurov A.S.

In this work, we studied the pharmacological activity of zinc and magnesium salts of 2-aminoethanesulfonic acid in white non-linear male rats with amyotrophic lateral sclerosis, which was modeled by neurotoxicantsimplication into the pelvic part of spinal cord. After the reproduction of the pathology in animals, the indices of motor activity were recorded in the Rotarod test, and morphological studies of spinal cord sections stained according to Nisl in the Belshovsky modification were carried out. It was shown that the magnesium salt of 2-aminoethanesulfonic acid (compound LHT-317) to a greater extent reduces the development of motor disorders in experimental animals compared with the control group on the 4th day of observation. The course of intravenous administration of the studied compounds of 2-aminoethanesulfonic acid did not inhibit morphological changes in the spinal cord that develop in degenerative-dystrophic pathology of the central nervous system: connections. Moreover, if, against the background of treatment with zinc salt, the total area of motor zones in animals of the experimental group exceeded that of control rats, then the number of motoneurons did not differ from the control.


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