scholarly journals Neuronal responses to tactile stimuli and tactile sensations evoked by microstimulation in the human thalamic principal somatic sensory nucleus (ventral caudal)

2016 ◽  
Vol 115 (5) ◽  
pp. 2421-2433 ◽  
Author(s):  
Anne-Christine Schmid ◽  
Jui-Hong Chien ◽  
Joel D. Greenspan ◽  
Ira Garonzik ◽  
Nirit Weiss ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Nervous System ◽  
Single Neuron ◽  
The Body ◽  
Neuronal Responses ◽  
Tactile Stimuli ◽  
Sensory Nucleus ◽  
Tactile Sensations ◽  
Sensory Abnormality

The normal organization and plasticity of the cutaneous core of the thalamic principal somatosensory nucleus (ventral caudal, Vc) have been studied by single-neuron recordings and microstimulation in patients undergoing awake stereotactic operations for essential tremor (ET) without apparent somatic sensory abnormality and in patients with dystonia or chronic pain secondary to major nervous system injury. In patients with ET, most Vc neurons responded to one of the four stimuli, each of which optimally activates one mechanoreceptor type. Sensations evoked by microstimulation were similar to those evoked by the optimal stimulus only among rapidly adapting neurons. In patients with ET, Vc was highly segmented somatotopically, and vibration, movement, pressure, and sharp sensations were usually evoked by microstimulation at separate sites in Vc. In patients with conditions including spinal cord transection, amputation, or dystonia, RFs were mismatched with projected fields more commonly than in patients with ET. The representation of the border of the anesthetic area (e.g., stump) or of the dystonic limb was much larger than that of the same part of the body in patients with ET. This review describes the organization and reorganization of human Vc neuronal activity in nervous system injury and dystonia and then proposes basic mechanisms.

scholarly journals Role of the immune system in neuropathic pain

2019 ◽  
Vol 20 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Marzia Malcangio
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Immune System ◽  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Immune Cells ◽  
Peripheral Nerve Injury

AbstractBackgroundAcute pain is a warning mechanism that exists to prevent tissue damage, however pain can outlast its protective purpose and persist beyond injury, becoming chronic. Chronic Pain is maladaptive and needs addressing as available medicines are only partially effective and cause severe side effects. There are profound differences between acute and chronic pain. Dramatic changes occur in both peripheral and central pathways resulting in the pain system being sensitised, thereby leading to exaggerated responses to noxious stimuli (hyperalgesia) and responses to non-noxious stimuli (allodynia).Critical role for immune system cells in chronic painPreclinical models of neuropathic pain provide evidence for a critical mechanistic role for immune cells in the chronicity of pain. Importantly, human imaging studies are consistent with preclinical findings, with glial activation evident in the brain of patients experiencing chronic pain. Indeed, immune cells are no longer considered to be passive bystanders in the nervous system; a consensus is emerging that, through their communication with neurons, they can both propagate and maintain disease states, including neuropathic pain. The focus of this review is on the plastic changes that occur under neuropathic pain conditions at the site of nerve injury, the dorsal root ganglia (DRG) and the dorsal horn of the spinal cord. At these sites both endothelial damage and increased neuronal activity result in recruitment of monocytes/macrophages (peripherally) and activation of microglia (centrally), which release mediators that lead to sensitisation of neurons thereby enabling positive feedback that sustains chronic pain.Immune system reactions to peripheral nerve injuriesAt the site of peripheral nerve injury following chemotherapy treatment for cancer for example, the occurrence of endothelial activation results in recruitment of CX3C chemokine receptor 1 (CX3CR1)-expressing monocytes/macrophages, which sensitise nociceptive neurons through the release of reactive oxygen species (ROS) that activate transient receptor potential ankyrin 1 (TRPA1) channels to evoke a pain response. In the DRG, neuro-immune cross talk following peripheral nerve injury is accomplished through the release of extracellular vesicles by neurons, which are engulfed by nearby macrophages. These vesicles deliver several determinants including microRNAs (miRs), with the potential to afford long-term alterations in macrophages that impact pain mechanisms. On one hand the delivery of neuron-derived miR-21 to macrophages for example, polarises these cells towards a pro-inflammatory/pro-nociceptive phenotype; on the other hand, silencing miR-21 expression in sensory neurons prevents both development of neuropathic allodynia and recruitment of macrophages in the DRG.Immune system mechanisms in the central nervous systemIn the dorsal horn of the spinal cord, growing evidence over the last two decades has delineated signalling pathways that mediate neuron-microglia communication such as P2X4/BDNF/GABAA, P2X7/Cathepsin S/Fractalkine/CX3CR1, and CSF-1/CSF-1R/DAP12 pathway-dependent mechanisms.Conclusions and implicationsDefinition of the modalities by which neuron and immune cells communicate at different locations of the pain pathway under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction and provides opportunities for novel approaches for the treatment of chronic pain.

Ascending pathways in the spinal cord involved in the activation of subnucleus reticularis dorsalis neurons in the medulla of the rat

1990 ◽  
Vol 63 (3) ◽  
pp. 424-438 ◽  
Author(s):  
Z. Bing ◽  
L. Villanueva ◽  
D. Le Bars
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
The Body ◽  
Cervical Cord ◽  
Lateral Part ◽  
Neuronal Responses ◽  
C Fiber ◽  
Dorsal Columns ◽  
Dorsolateral Funiculus ◽  
The Right

1. Recordings were made from neurons in the left medullary subnucleus reticularis dorsalis (SRD) of anesthetized rats. Two populations of neurons were recorded: neurons with total nociceptive convergence (TNC), which gave responses to A delta- and C-fiber activation from the entire body after percutaneous electrical stimulation, and neurons with partial nociceptive convergence (PNC), which responded to identical stimuli with an A delta-peak regardless of which part of the body was stimulated and with a C-fiber peak of activation from some, mainly contralateral, parts of the body. 2. The effects of various, acute, transverse sections of the cervical (C4-C5) spinal cord on the A delta- and C-fiber-evoked responses were investigated by building poststimulus histograms (PSHs) after 50 trials of supramaximal percutaneous electrical stimulation of the extremity of either hindpaw (2-ms duration; 3 times threshold for C-fiber responses), before and 30-40 min after making the spinal lesion. 3. In the case of TNC neurons, hemisections of the left cervical cord blocked the responses elicited from the right hindpaw and slightly, but not significantly, diminished those evoked from the left hindpaw. Conversely, hemisections of the right cervical cord abolished TNC responses elicited from the left hindpaw without significantly affecting the responses elicited from the right hindpaw. 4. Lesioning the dorsal columns or the left dorsolateral funiculus was found not to affect the TNC neuronal responses elicited from either hindpaw. By contrast, lesioning the left lateral funiculus or the most lateral part of the ventrolateral funiculus, respectively, reduced and blocked the responses elicited from the right hindpaw without affecting those evoked from the left hindpaw. 5. After lesions that included the most lateral parts of the left ventral funiculus, PNC neuronal responses elicited from the right hindpaw were also abolished, whereas those elicited from the left hindpaw remained unchanged. 6. We conclude that the signals responsible for the activation of SRD neurons travel principally in the lateral parts of the ventrolateral quadrant, a region that classically has been implicated in the transmission of noxious information. Both a crossed and a double-crossed pathway are involved in this process. The postsynaptic fibers of the dorsal columns and the spinocervical and spinomesencephalic tracts do not appear to convey signals that activate SRD neurons. 7. The findings also suggest that lamina I nociceptive specific neurons, the axons of which travel within the dorsolateral funiculus, do not contribute very much to the activation of SRD neurons.

Modifications of Locomotor Pattern Underlying Escape Behavior in the Lamprey

2008 ◽  
Vol 99 (1) ◽  
pp. 297-307 ◽  
Author(s):  
Salma S. Islam ◽  
Pavel V. Zelenin
Keyword(s):  
Spinal Cord ◽  
Escape Behavior ◽  
Sensory Information ◽  
The Body ◽  
Descending Pathways ◽  
Long Distance ◽  
Lower Vertebrate ◽  
Dorsal Roots ◽  
Tactile Stimuli ◽  
Undulatory Locomotion

Two forms of undulatory locomotion in the lamprey (a lower vertebrate) have been described earlier: fast forward swimming (FFS) used for long distance migrations and slow backward swimming (SBS) used for escape from adverse tactile stimuli. In the present study, we describe another form of escape behavior: slow forward swimming (SFS). We characterize the kinematic and electromyographic patterns of SFS and compare them with SBS and FFS. The most striking feature of SFS is nonuniformity of shape and speed of the locomotor waves propagating along the body: close to the site of stimulation, the waves slow down and the body curvature increases several-fold due to enhanced muscle activity. Lesions of afferents showed that sensory information critical for elicitation of SFS is transmitted through the dorsal roots. In contrast, sensory signals that induce SBS are transmitted through the dorsal roots, lateral line nerves, and trigeminal nerves. Persistence of SFS and SBS after different lesions of the spinal cord suggests that the ascending and descending pathways, necessary for induction of SBS and SFS, are dispersed over the cross section of the spinal cord. As shown previously, during FFS (but not SBS) the lamprey maintains the dorsal-side-up body orientation due to vestibular postural reflexes. In this study we have found that the orientation control is absent during SFS. The role of the spinal cord and the brain stem in generation of different forms of undulatory locomotion is discussed.

scholarly journals Modulation of Glia-Mediated Processes by Spinal Cord Stimulation in Animal Models of Neuropathic Pain

2021 ◽  
Vol 2 ◽  
Author(s):  
David L. Cedeño ◽  
Courtney A. Kelley ◽  
Krishnan Chakravarthy ◽  
Ricardo Vallejo
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Glial Cells ◽  
Mechanism Of Action ◽  
Spinal Cord Stimulation ◽  
Expression Levels ◽  
Gate Control Theory

Glial cells play an essential role in maintaining the proper functioning of the nervous system. They are more abundant than neurons in most neural tissues and provide metabolic and catabolic regulation, maintaining the homeostatic balance at the synapse. Chronic pain is generated and sustained by the disruption of glia-mediated processes in the central nervous system resulting in unbalanced neuron–glial interactions. Animal models of neuropathic pain have been used to demonstrate that changes in immune and neuroinflammatory processes occur in the course of pain chronification. Spinal cord stimulation (SCS) is an electrical neuromodulation therapy proven safe and effective for treating intractable chronic pain. Traditional SCS therapies were developed based on the gate control theory of pain and rely on stimulating large Aβ neurons to induce paresthesia in the painful dermatome intended to mask nociceptive input carried out by small sensory neurons. A paradigm shift was introduced with SCS treatments that do not require paresthesia to provide effective pain relief. Efforts to understand the mechanism of action of SCS have considered the role of glial cells and the effect of electrical parameters on neuron–glial interactions. Recent work has provided evidence that SCS affects expression levels of glia-related genes and proteins. This inspired the development of a differential target multiplexed programming (DTMP) approach using electrical signals that can rebalance neuroglial interactions by targeting neurons and glial cells differentially. Our group pioneered the utilization of transcriptomic and proteomic analyses to identify the mechanism of action by which SCS works, emphasizing the DTMP approach. This is an account of evidence demonstrating the effect of SCS on glia-mediated processes using neuropathic pain models, emphasizing studies that rely on the evaluation of large sets of genes and proteins. We show that SCS using a DTMP approach strongly affects the expression of neuron and glia-specific transcriptomes while modulating them toward expression levels of healthy animals. The ability of DTMP to modulate key genes and proteins involved in glia-mediated processes affected by pain toward levels found in uninjured animals demonstrates a shift in the neuron–glial environment promoting analgesia.

Introduction to the Nervous System

2017 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
The Body ◽  
Conscious Awareness ◽  
Sensory Stimuli ◽  
System P ◽  
Brainstem Stroke ◽  
Primary Deficit ◽  
The Central Nervous System ◽  
The Brain

The primary regions and principal functions of the central nervous system are introduced through the story of Jean-Dominique Bauby who became locked in after suffering a brainstem stroke. Bauby blinked out his story of locked-in syndrome one letter at a time. The primary deficit of locked-in syndrome is in voluntary movement because pathways from the brain to motoneurons in the brainstem and spinal cord are interrupted. Perception is also disturbed as pathways responsible for transforming sensory stimuli into conscious awareness are interrupted as they ascend through the brainstem into the forebrain. Homeostasis, through which the brain keeps the body alive, is also adversely affected in locked-in syndrome because it depends on the brain, spinal cord and autonomic nervous system. Abstract functions such as memory, language, and emotion depend fully on the forebrain and are intact in locked-in syndrome, as clearly evidenced by Bauby’s eloquent words.

Characteristics of somatotopic organization and spontaneous neuronal activity in the region of the thalamic principal sensory nucleus in patients with spinal cord transection

1994 ◽  
Vol 72 (4) ◽  
pp. 1570-1587 ◽  
Author(s):  
F. A. Lenz ◽  
H. C. Kwan ◽  
R. Martin ◽  
R. Tasker ◽  
R. T. Richardson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Poisson Distribution ◽  
Neuronal Activity ◽  
High Frequency ◽  
Spike Trains ◽  
The Body ◽  
Border Zone ◽  
Sensory Nucleus ◽  
Spontaneous Neuronal Activity ◽  
Spinal Control

1. We explored the region of the principal sensory nucleus of thalamus (Vc) during stereotactic surgical procedures for treatment of patients with pain after spinal cord transection (n = 23). Receptive fields (RFs) of thalamic single neurons and locations of sensations evoked by stimulation (projected field, PF) were determined by standard methods. The cellular thalamic region where sensations were evoked at < 25 microA was termed the “region of Vc.” The region of Vc in spinal patients was subdivided into different areas according to RF and PF locations. Areas that were distant from the representation of the anesthetic part of the body were termed “spinal control” areas, whereas those that were adjacent to or included in the representation of the area of absolute sensory loss were termed “border zone/anesthetic” areas. The region of Vc in movement disorder patients were termed the “control” area. 2. Border zone/anesthetic areas of thalamus often exhibited increased representations of the border of the anesthetic part of the body in comparison with the representation of the same parts of the body in control and spinal control areas. 3. In control and spinal control areas the locations of RFs and PFs were usually well matched. However, in border zone/anesthetic areas of the thalamus there was frequently a mismatch between the location of RFs and PFs (RF/PF mismatch). In border zone/anesthetic areas, RFs were often located on the border of the anesthetic part of the body whereas PFs were referred to anesthetic parts of the body. 4. Analysis of first- and higher-order properties of spontaneous neuronal activity revealed that spike trains could be classified into two groups with distinct patterns of activity. The R group (n = 49) was characterized by independence of sequential interspike intervals (ISIs), a Poisson distribution of ISIs, initially inhibitory or flat autocovariance function (acvf), and low level of high-frequency bursting. The O group (n = 26) was characterized by correlation of sequential ISIs, large sustained postspike facilitation on the acvf, and high prevalence of high-frequency bursting--all consistent with a bursting pattern of activity. A third group of spike trains (n = 17) had an initially inhibitory or flat acvf and a unimodal, positively shifted, ISI distribution that did not meet criteria for a Poisson distribution. 5. Spike trains in the R group were much more common in control and control spinal areas, whereas those in the O group were more common in border zone/anesthetic areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Why and How Do We Hurt?

2002 ◽  
Author(s):  
Daniel J. Wallace ◽  
Janice Brock Wallace
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Clinical Situation ◽  
The Body ◽  
Sensory Pathways ◽  
System P ◽  
Chronic Pain Patients ◽  
The Central Nervous System ◽  
Pain Patients ◽  
The Brain

A fibromyalgia patient frequently complains of pain. The pain of fibromyalgia is different from that of a headache, stomach cramp, toothache, or swollen joint. It has been described as a type of stiffness or aching, often associated with spasm. Unlike the other pains mentioned above, fibromyalgia pain responds poorly to aspirin, acetaminophen (Tylenol), or ibuprofen (Advil, Motrin). In fact, studies have suggested that even narcotics such as morphine are minimally beneficial in ameliorating fibromyalgia pain. Why is it that fibromyalgia patients can take codeine, Darvon, Vicodin, or even Demerol for musculoskeletal aches and have only a slight response? What produces “pain without purpose”? In this chapter, we’ll explore what makes fibromyalgia a pain amplification syndrome. Why does the patient hurt in places where there was often no injury and all laboratory tests are normal? What creates what doctors call allodynia, or a clinical situation that results in pain from a stimulus (such as light touch) that normally should not be painful? Fibromyalgia is a form of chronic, widespread allodynia, as well as sustained hyperalgesia, or greater sensitivity than would be expected to an adverse stimulus. The nervous system consists of several components. The brain and spinal cord comprise the central nervous system. Nerves leaving the spinal cord that tell us to move our arms or legs are part of the “motor” aspects of the peripheral nervous system. Additionally, all sorts of information about touch, taste, chemicals, and pressure are relayed through “sensory” pathways back to the spinal cord, where they are processed and sent up to the brain for a response. The autonomic nervous system consists of specialized peripheral nerves. Fibromyalgia is a disorder characterized by an inappropriate neuromuscular reaction that leads to chronic pain. Patients with fibromyalgia usually react normally to acute pain. Our current concepts of the way the body responds to chronic painful stimuli stem from the gate theory, first proposed by Ronald Melzack and Patrick Wall in 1965. Nerve “wires” go from the periphery to the dorsal horn of the spinal cord. These wires are modulated by feedback loops within the nervous system.

THE INFLUENCE OF SEX ON THE MATURATION OF THE CENTRAL NERVOUS SYSTEM IN THE ALBINO RAT

1951 ◽  
Vol 7 (3) ◽  
pp. 271-279 ◽  
Author(s):  
J. T. EAYRS
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
The Body ◽  
Female Rats ◽  
Male Rats ◽  
Albino Rat ◽  
Litter Mate ◽  
Male And Female Rats ◽  
The Central Nervous System

The growth of the body and central nervous system and the emergence of stereotyped behaviour have been studied in male and female rats during the first 24 days of life. The effects of daily injections of equine gonadotrophin on these measures have also been investigated. The weight of the body and of the central nervous system was significantly less in the female than in the male. The daily administration of 10 i.u. of equine gonadotrophin was without effect on either. The movements of the trunk and limbs concerned in the body-righting reflex became coordinated more slowly in the gonadotrophin-injected animals than in their litter-mate controls. At 15 days old, male rats were able to right in mid-air more successfully than litter-mate females. The placing reflex appeared earlier in the male than in the female. Its appearance was accelerated in the females given gonadotrophin, but not in the males. In the ventral funiculus of the spinal cord of 24-day-old experimental animals, the axis cylinders occupied more space relative to that occupied by myelin than did those of the controls. The total amount of myelin present was unchanged. There was no sex difference in the progress of myelination in the spinal cord. The significance of these findings in relation to the secretion of sex hormones is discussed. It is suggested that the secretion of androgen may be responsible for an acceleration of nervous maturation.

scholarly journals VI. Croonian Lecture.—On the mammalian nervous system, its functions, and their localisation determined by an electrical method

1891 ◽  
Vol 182 ◽  
pp. 267-526 ◽  
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Internal Capsule ◽  
The Body ◽  
Full Detail ◽  
Electrical Method ◽  
Cortex Cerebri ◽  
The Central Nervous System ◽  
Motor Nerves ◽  
Central Apparatus

In the 'Proceedings of the Royal Society,' vol. 45, 1889, p. 18 (Meeting of November 1, 1888), we published a preliminary account of some of the experiments of which the results are now given in full detail. In that communication we stated that the object of our work then was to endeavour to ascertain the character of the excitatory processes occurring in nerve fibres, when, either directly (artificially) excited, or when in that state of functional activity, which is due to the passage of impulses along them from the central apparatus. The most important way in which such a method could be applied was obviously one which would involve the investigation of the excitatory changes occurring in the fibres of the spinal cord when the cortex cerebri is stimulated. We must at once assume that the motor side of the central nervous system is practically divisible into three elements:— 1. Cortical centres. 2. Efferent (pyramidal tract) fibres leading down through the internal capsule, corona radiata, and spinal cord. 3. Bulbo-spinal centres contained in the medulla and the spinal cord, and forming the well-known nuclei of the cranial and also of the spinal motor nerves. It had already been determined, both by direct observation and by the graphic method (1) that certain areas of the cortex were connected with definite movements of various parts of the body, and (2) that while the complete discharge of the cortical apparatus was followed by a very definite and characteristic series of contractions of the muscles in special relation with the particular point excited, the effectual removal of the cortical central mechanisn and subsequent excitation of the white fibres passing down through the internal capsule, &c., led to the production of only a portion of the effect previously obtained from the uninjured brain.

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