scholarly journals Investigating Circadian Rhythmicity in Pain Sensitivity Using a Neural Circuit Model for Spinal Cord Processing of Pain

2017 ◽  
pp. 23-48
Author(s):  
Jennifer A. Crodelle ◽  
Sofia H. Piltz ◽  
Victoria Booth ◽  
Megan Hastings Hagenauer
Keyword(s):  
Spinal Cord ◽  
Pain Sensitivity ◽  
Neural Circuit ◽  
Circuit Model ◽  
Circadian Rhythmicity

scholarly journals Investigating circadian rhythmicity in pain sensitivity using a neural circuit model for spinal cord processing of pain

2017 ◽  
Author(s):  
Jennifer A. Crodelle ◽  
Sofia H. Piltz ◽  
Victoria Booth ◽  
Megan Hastings Hagenauer
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Neural Circuit ◽  
Dynamic Range ◽  
Nerve Fibers ◽  
Circadian Rhythmicity ◽  
Noxious Stimulation ◽  
Peripheral Tissues ◽  
Pain Signal

AbstractPrimary processing of painful stimulation occurs in the dorsal horn of the spinal cord. In this article, we introduce mathematical models of the neural circuitry in the dorsal horn responsible for processing nerve fiber inputs from noxious stimulation of peripheral tissues and generating the resultant pain signal. The differential equation models describe the average firing rates of excitatory and inhibitory interneuron populations, as well as the wide dynamic range (WDR) neurons whose output correlates with the pain signal. The temporal profile of inputs on the different afferent nerve fibers that signal noxious and innocuous stimulation and the excitability properties of the included neuronal populations are constrained by experimental results. We consider models for the spinal cord circuit in isolation and when top-down inputs from higher brain areas that modulate pain processing are included. We validate the models by replicating experimentally observed phenomena of A fiber inhibition of pain and wind-up. We then use the models to investigate mechanisms for the observed phase shift in circadian rhythmicity of pain that occurs with neuropathic pain conditions. Our results suggest that changes in neuropathic pain rhythmicity can occur through dysregulation of inhibition within the dorsal horn circuit.

Neural Mechanisms of Hyperalgesia: Peripheral or Central Sensitization?

Physiology ◽  
1995 ◽  
Vol 10 (6) ◽  
pp. 260-265
Author(s):  
E Carstens
Keyword(s):  
Spinal Cord ◽  
Central Sensitization ◽  
Pain Sensitivity ◽  
Neural Mechanisms ◽  
Neural Processes

Everyone has experienced soreness after an injury. What neural processes underlie this increased pain sensitivity (hyperalgesia)? Recent data indicate that injury triggers an increase in the sensitivity of spinal cord pain-signaling neurons. Nonpainful activation of these sensitized neurons evokes an exaggerated signal interpreted as pain.

scholarly journals Effect of Artesunate on Leishmania Amazonesis Induced Neuroinflammation and Nociceptive Behavior in Male Balb/C Mice

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 557
Author(s):  
Enrico Gugliandolo ◽  
Ernesto Palma ◽  
Alessio Filippo Peritore ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Spinal Cord ◽  
Neurological Disorders ◽  
Pain Sensitivity ◽  
Nociceptive Behavior ◽  
Sickness Behaviors ◽  
Inflammatory State ◽  
The Central Nervous System ◽  
Spinal Cord Level

Background: Leishmaniasis is a multisystemic zoonotic disease with several symptoms, including neurological disorders. Leishmaniasis is accompanied by an increase in nociceptive behaviors, linked to the presence of a chronic inflammatory state, in both peripheral tissue and the central nervous system. Artesunate is a more stable derivative of its precursor artemisin and has been shown to be a pluripotent agent with different pharmacological actions. Methods: In this study, we investigated the effects of artesunate in Leishmania amazonensi- infected BALB/c mice, evaluating its effectiveness in reducing inflammation, neuroinflammation, and nociceptive and sickness behaviors. Results: Our results demonstrate a significant increase in pain sensitivity and sickness behaviors after L. amazonensis infection. Moreover, the infection induced a significant increase in inflammatory response at both the paw and spinal cord level. Treatment with artesunate was able to induce a significant decrease in tissue inflammation and neuroinflammation and thus induce a significant decrease in pain sensitivity and sickness behaviors. Conclusions: The results from this study indicate that artesunate is a good candidate for treatment and/or as an adjuvant in leishmanicidal therapy, and to prevent and alleviate leishmaniasis-induced pain and neuroinflammation and thereby improve the quality of life of leishmaniasis patients.

scholarly journals Mis-expression of the BK K+ channel disrupts suprachiasmatic nucleus circuit rhythmicity and alters clock-controlled behavior

2013 ◽  
Vol 304 (4) ◽  
pp. C299-C311 ◽  
Author(s):  
Jenna R. Montgomery ◽  
Joshua P. Whitt ◽  
Breanne N. Wright ◽  
Michael H. Lai ◽  
Andrea L. Meredith
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Neural Circuit ◽  
High Amplitude ◽  
Circadian Rhythmicity ◽  
K Channel ◽  
Current Channel ◽  
Behavioral Rhythm ◽  
Ionic Mechanisms ◽  
Almost All ◽  
Circadian Behavior

In mammals, almost all aspects of circadian rhythmicity are attributed to activity in a discrete neural circuit of the hypothalamus, the suprachiasmatic nucleus (SCN). A 24-h rhythm in spontaneous firing is the fundamental neural intermediary to circadian behavior, but the ionic mechanisms that pattern circuit rhythmicity, and the integrated impact on behavior, are not well studied. Here, we demonstrate that daily modulation of a major component of the nighttime-phased suppressive K+ current, encoded by the BK Ca2+-activated K+ current channel (KCa1.1 or Kcnma1), is a critical arbiter of circadian rhythmicity in the SCN circuit. Aberrant induction of BK current during the day in transgenic mice using a Per1 promoter ( Tg-BK R207Q) reduced SCN firing or silenced neurons, decreasing the circadian amplitude of the ensemble circuit rhythm. Changes in cellular and circuit excitability in Tg-BK R207Q SCNs were correlated with elongated behavioral active periods and enhanced responses to phase-shifting stimuli. Unexpectedly, despite the severe reduction in circuit amplitude, circadian behavioral amplitudes in Tg-BK R207Q mice were relatively normal. These data demonstrate that downregulation of the BK current during the day is essential for the high amplitude neural activity pattern in the SCN that restricts locomotor activity to the appropriate phase and maintains the clock's robustness against perturbation. However, a residually rhythmic subset prevails over the ensemble circuit to drive the fundamental circadian behavioral rhythm.

A Dynamic Body Model of the NematodeC. eleganswith Neural Oscillators

2005 ◽  
Vol 17 (3) ◽  
pp. 318-326 ◽  
Author(s):  
Michiyo Suzuki ◽  
◽  
Takeshi Goto ◽  
Toshio Tsuji ◽  
Hisao Ohtake ◽  
...  
Keyword(s):  
Computer Simulation ◽  
Motor Control ◽  
Caenorhabditis Elegans ◽  
Neural Circuit ◽  
Rhythmic Movement ◽  
Circuit Model ◽  
Neural Oscillators ◽  
C Elegans ◽  
Body Model ◽  
Multicellular Organisms

The nematode <I>Caenorhabditis elegans (C. elegans)</I>, a relatively simple organism in structure, is one of the most well-studied multicellular organisms. We developed a <I>virtual C. elegans</I> based on the actual organism to analyze motor control. We propose a dynamic body model, including muscles, controlled by a neural circuit model based on the actual nematode. The model uses neural oscillators to generate rhythmic movement. Computer simulation confirmed that the <I>virtual C. elegans</I> realizes motor control similar qualitatively to that of the actual organism. Specified classes of neurons are killed in the neural circuit model corresponding to actual <I>unc</I> mutants, demonstrating that resulting movement of the <I>virtual C. elegans</I> resembles that of actual mutants.

scholarly journals MicroRNAs mediate precise control of spinal interneuron populations to exert delicate sensory-to-motor outputs

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Shih-Hsin Chang ◽  
Yi-Ching Su ◽  
Mien Chang ◽  
Jun-An Chen
Keyword(s):  
Spinal Cord ◽  
Neural Circuit ◽  
Thermally Induced ◽  
Precise Control ◽  
Dynamic Expression ◽  
Spinal Interneuron ◽  
Motor Synergy ◽  
Response Thresholds ◽  
Fine Tune ◽  
Behavioral Assays

Although the function of microRNAs (miRNAs) during embryonic development has been intensively studied in recent years, their postnatal physiological functions remain largely unexplored due to inherent difficulties with the presence of redundant paralogs of the same seed. Thus, it is particularly challenging to uncover miRNA functions at neural circuit level since animal behaviors would need to be assessed upon complete loss of miRNA family functions. Here, we focused on the neural functions of MiR34/449 that manifests a dynamic expression pattern in the spinal cord from embryonic to postnatal stages. Our behavioral assays reveal that the loss of MiR34/449 miRNAs perturb thermally induced pain response thresholds and compromised delicate motor output in mice. Mechanistically, MiR34/449 directly target Satb1 and Satb2 to fine-tune the precise number of a sub-population of motor synergy encoder (MSE) neurons. Thus, MiR34/449 fine-tunes optimal development of Satb1/2on interneurons in the spinal cord, thereby refining explicit sensory-to-motor circuit outputs.

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