scholarly journals Systems and Circuits Linking Chronic Pain and Circadian Rhythms

2021 ◽  
Vol 15 ◽  
Author(s):  
Andrew E. Warfield ◽  
Jonathan F. Prather ◽  
William D. Todd
Keyword(s):  
Chronic Pain ◽  
Circadian Rhythms ◽  
Intracellular Signaling ◽  
Clock Gene ◽  
Cell Types ◽  
Sexually Dimorphic ◽  
Clock Gene Expression ◽  
Bidirectional Relationship ◽  
And Behavior ◽  
The Brain

Research over the last 20 years regarding the link between circadian rhythms and chronic pain pathology has suggested interconnected mechanisms that are not fully understood. Strong evidence for a bidirectional relationship between circadian function and pain has been revealed through inflammatory and immune studies as well as neuropathic ones. However, one limitation of many of these studies is a focus on only a few molecules or cell types, often within only one region of the brain or spinal cord, rather than systems-level interactions. To address this, our review will examine the circadian system as a whole, from the intracellular genetic machinery that controls its timing mechanism to its input and output circuits, and how chronic pain, whether inflammatory or neuropathic, may mediate or be driven by changes in these processes. We will investigate how rhythms of circadian clock gene expression and behavior, immune cells, cytokines, chemokines, intracellular signaling, and glial cells affect and are affected by chronic pain in animal models and human pathologies. We will also discuss key areas in both circadian rhythms and chronic pain that are sexually dimorphic. Understanding the overlapping mechanisms and complex interplay between pain and circadian mediators, the various nuclei they affect, and how they differ between sexes, will be crucial to move forward in developing treatments for chronic pain and for determining how and when they will achieve their maximum efficacy.

scholarly journals Circadian influences on dopamine circuits of the brain: regulation of striatal rhythms of clock gene expression and implications for psychopathology and disease

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2062 ◽  
Author(s):  
Michael Verwey ◽  
Sabine Dhir ◽  
Shimon Amir
Keyword(s):  
Gene Expression ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Clock Gene ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Physiological Importance ◽  
Clock Gene Expression ◽  
Dopamine Circuits ◽  
The Brain

Circadian clock proteins form an autoregulatory feedback loop that is central to the endogenous generation and transmission of daily rhythms in behavior and physiology. Increasingly, circadian rhythms in clock gene expression are being reported in diverse tissues and brain regions that lie outside of the suprachiasmatic nucleus (SCN), the master circadian clock in mammals. For many of these extra-SCN rhythms, however, the region-specific implications are still emerging. In order to gain important insights into the potential behavioral, physiological, and psychological relevance of these daily oscillations, researchers have begun to focus on describing the neurochemical, hormonal, metabolic, and epigenetic contributions to the regulation of these rhythms. This review will highlight important sites and sources of circadian control within dopaminergic and striatal circuitries of the brain and will discuss potential implications for psychopathology and disease. For example, rhythms in clock gene expression in the dorsal striatum are sensitive to changes in dopamine release, which has potential implications for Parkinson’s disease and drug addiction. Rhythms in the ventral striatum and limbic forebrain are sensitive to psychological and physical stressors, which may have implications for major depressive disorder. Collectively, a rich circadian tapestry has emerged that forces us to expand traditional views and to reconsider the psychopathological, behavioral, and physiological importance of these region-specific rhythms in brain areas that are not immediately linked with the regulation of circadian rhythms.

scholarly journals Casein Kinase 1 Underlies Temperature Compensation of Circadian Rhythms in Human Red Blood Cells

2019 ◽  
Vol 34 (2) ◽  
pp. 144-153 ◽  
Author(s):  
Andrew D. Beale ◽  
Emily Kruchek ◽  
Stephen J. Kitcatt ◽  
Erin A. Henslee ◽  
Jack S.W. Parry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Rhythms ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Temperature Compensation ◽  
Clock Gene ◽  
Cell Types ◽  
Casein Kinase ◽  
Casein Kinase 1 ◽  
Human Red Blood Cells

Temperature compensation and period determination by casein kinase 1 (CK1) are conserved features of eukaryotic circadian rhythms, whereas the clock gene transcription factors that facilitate daily gene expression rhythms differ between phylogenetic kingdoms. Human red blood cells (RBCs) exhibit temperature-compensated circadian rhythms, which, because RBCs lack nuclei, must occur in the absence of a circadian transcription-translation feedback loop. We tested whether period determination and temperature compensation are dependent on CKs in RBCs. As with nucleated cell types, broad-spectrum kinase inhibition with staurosporine lengthened the period of the RBC clock at 37°C, with more specific inhibition of CK1 and CK2 also eliciting robust changes in circadian period. Strikingly, inhibition of CK1 abolished temperature compensation and increased the Q10 for the period of oscillation in RBCs, similar to observations in nucleated cells. This indicates that CK1 activity is essential for circadian rhythms irrespective of the presence or absence of clock gene expression cycles.

scholarly journals Glucocorticoid receptor action in metabolic and neuronal function

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1208 ◽  
Author(s):  
Michael J. Garabedian ◽  
Charles A. Harris ◽  
Freddy Jeanneteau
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptor ◽  
Metabolic Diseases ◽  
Cell Types ◽  
Health And Disease ◽  
And Behavior ◽  
External Signals ◽  
The Brain

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them.

scholarly journals Physiology of Circadian Entrainment

2010 ◽  
Vol 90 (3) ◽  
pp. 1063-1102 ◽  
Author(s):  
Diego A. Golombek ◽  
Ruth E. Rosenstein
Keyword(s):  
Circadian Rhythms ◽  
Clock Gene ◽  
Retinal Diseases ◽  
Suprachiasmatic Nuclei ◽  
Circadian Variations ◽  
Dark Cycle ◽  
Clock Gene Expression ◽  
Biological Oscillators ◽  
Pituitary Adenylate Cyclase ◽  
Neurotransmitter Glutamate

Mammalian circadian rhythms are controlled by endogenous biological oscillators, including a master clock located in the hypothalamic suprachiasmatic nuclei (SCN). Since the period of this oscillation is of ∼24 h, to keep synchrony with the environment, circadian rhythms need to be entrained daily by means of Zeitgeber (“time giver”) signals, such as the light-dark cycle. Recent advances in the neurophysiology and molecular biology of circadian rhythmicity allow a better understanding of synchronization. In this review we cover several aspects of the mechanisms for photic entrainment of mammalian circadian rhythms, including retinal sensitivity to light by means of novel photopigments as well as circadian variations in the retina that contribute to the regulation of retinal physiology. Downstream from the retina, we examine retinohypothalamic communication through neurotransmitter (glutamate, aspartate, pituitary adenylate cyclase-activating polypeptide) interaction with SCN receptors and the resulting signal transduction pathways in suprachiasmatic neurons, as well as putative neuron-glia interactions. Finally, we describe and analyze clock gene expression and its importance in entrainment mechanisms, as well as circadian disorders or retinal diseases related to entrainment deficits, including experimental and clinical treatments.

scholarly journals Neuron-specific knockouts indicate the importance of network communication to Drosophila rhythmicity

2019 ◽  
Author(s):  
M Schlichting ◽  
MM Diaz ◽  
J Xin ◽  
M Rosbash
Keyword(s):  
Gene Expression ◽  
Circadian Rhythms ◽  
Intercellular Communication ◽  
Clock Gene ◽  
Feedback Loops ◽  
Neuronal Firing ◽  
Network Communication ◽  
Constant Darkness ◽  
Circadian Period ◽  
Clock Gene Expression

AbstractAnimal circadian rhythms persist in constant darkness and are driven by intracellular transcription-translation feedback loops. Although these cellular oscillators communicate, isolated mammalian cellular clocks continue to tick away in darkness without intercellular communication. To investigate these issues in Drosophila, we assayed behavior as well as molecular rhythms within individual brain clock neurons while blocking communication within the ca. 150 neuron clock network. We also generated CRISPR-mediated neuron-specific circadian clock knockouts. The results point to two key clock neuron groups: loss of the clock within both regions but neither one alone has a strong behavioral phenotype in darkness; communication between these regions also contributes to circadian period determination. Under these dark conditions, the clock within one region persists without network communication. The clock within the famous PDF-expressing s-LNv neurons however was strongly dependent on network communication, likely because clock gene expression within these vulnerable sLNvs depends on neuronal firing or light.

scholarly journals Artificial Light at Night Influences Clock-Gene Expression, Activity, and Fecundity in the Mosquito Culex pipiens f. molestus

2019 ◽  
Vol 11 (22) ◽  
pp. 6220 ◽  
Author(s):  
Honnen ◽  
Kypke ◽  
Hölker ◽  
Monaghan
Keyword(s):  
Gene Expression ◽  
Culex Pipiens ◽  
Clock Gene ◽  
Clock Cycle ◽  
Diel Activity ◽  
Artificial Light ◽  
Light At Night ◽  
Clock Gene Expression ◽  
Expression Activity ◽  
And Behavior

Light is an important environmental cue, and exposure to artificial light at night (ALAN) may disrupt organismal physiology and behavior. We investigated whether ALAN led to changes in clock-gene expression, diel activity patterns, and fecundity in laboratory populations of the mosquito Culex pipiens f. molestus (Diptera, Culicidae), a species that occurs in urban areas and is thus regularly exposed to ALAN. Populations were kept under 16hours (h):8h light:dark cycles or were subjected to an additional 3.5 h of light (100–300 lx) in the evenings. ALAN induced significant changes in expression in all genes studied, either alone (period) or as an interaction with time (timeless, cryptochrome2, Clock, cycle). Changes were sex-specific: period was down-regulated in both sexes, cycle was up-regulated in females, and Clock was down-regulated in males. ALAN-exposed mosquitoes were less active during the extra-light phase, but exposed females were more active later in the night. ALAN-exposed females also produced smaller and fewer eggs. Our findings indicate a sex-specific impact of ALAN on the physiology and behavior of Culex pipiens f. molestus and that changes in clock-gene expression, activity, and fecundity may be linked.

scholarly journals Minireview: The Neuroendocrinology of the Suprachiasmatic Nucleus as a Conductor of Body Time in Mammals

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5640-5647 ◽  
Author(s):  
Ilia N. Karatsoreos ◽  
Rae Silver
Keyword(s):  
Circadian Rhythms ◽  
Suprachiasmatic Nucleus ◽  
Hormone Secretion ◽  
Gonadal Hormone ◽  
Multiple Levels ◽  
And Behavior ◽  
Circadian Behavior ◽  
The Brain ◽  
Indirect Route ◽  
Photic Input

Circadian rhythms in physiology and behavior are regulated by a master clock resident in the suprachiasmatic nucleus (SCN) of the hypothalamus, and dysfunctions in the circadian system can lead to serious health effects. This paper reviews the organization of the SCN as the brain clock, how it regulates gonadal hormone secretion, and how androgens modulate aspects of circadian behavior known to be regulated by the SCN. We show that androgen receptors are restricted to a core SCN region that receives photic input as well as afferents from arousal systems in the brain. We suggest that androgens modulate circadian behavior directly via actions on the SCN and that both androgens and estrogens modulate circadian rhythms through an indirect route, by affecting overall activity and arousal levels. Thus, this system has multiple levels of regulation; the SCN regulates circadian rhythms in gonadal hormone secretion, and hormones feed back to influence SCN functions.

Sign in / Sign up

Export Citation Format

Share Document