Cortical Mechanisms for Emotional Fear and Chronic Pain

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
M. Zhuo
Keyword(s):  
Chronic Pain ◽  
Emotional Disorders ◽  
Cortical Neurons ◽  
Neural Mechanism ◽  
Anterior Cingulate ◽  
Cellular Mechanisms ◽  
New Genes ◽  
Trace Fear ◽  
The Brain ◽  
Synaptic Model

Investigation of molecular and cellular mechanisms of synaptic plasticity is the major focus of many neuroscientists. There are two major reasons for searching new genes and molecules contributing to central plasticity: first, it provides basic neural mechanism for learning and memory, a key function of the brain; second, it provides new targets for treating brain-related disease. Here, I propose that LTP in the anterior cingulate cortex (ACC) as a synaptic model for emotional fear and chronic pain in the brain. Integrative approaches including genetic, neurobiological and physiological methods are used to investigate the roles of cortical neurons and microglia in synaptic LTP, fear and chronic pain. We have identified several key calcium-stimulated signaling molecules including AC1, CaMKIV and FMRP for AMPA receptor mediated cingulate LTP, trace fear memory, and chronic pain. By contrast, microglia only contributes to changes in spinal dorsal horn, but not in the cortex. Our findings strongly suggest that ACC LTP may serve as a cellular model for studying central sensitization that related to fear and chronic pain, as well as pain-related cognitive emotional disorders.

scholarly journals Interplay of Amygdala and Cingulate Plasticity in Emotional Fear

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Hiroki Toyoda ◽  
Xiang-Yao Li ◽  
Long-Jun Wu ◽  
Ming-Gao Zhao ◽  
Giannina Descalzi ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Emotional Disorders ◽  
Cortical Neurons ◽  
Fear Memory ◽  
Anterior Cingulate ◽  
Cortical Areas ◽  
Freely Moving ◽  
Plastic Changes ◽  
Trace Fear ◽  
Synaptic Level

The amygdala is known to be a critical brain region for emotional fear. It is believed that synaptic plasticity within the amygdala is the cellular basis of fear memory. Recent studies demonstrate that cortical areas such as the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) may also contribute to the formation of fear memory, including trace fear memory and remote fear memory. At synaptic level, fear conditioning also triggers plastic changes within the cortical areas immediately after the condition. These results raise the possibility that certain forms of synaptic plasticity may occur within the cortex while synaptic potentiation takes place within synapses in the hippocampus and amygdala. This hypothesis is supported by electrophysiological evidence obtained from freely moving animals that neurons in the hippocampus/amygdala fire synchronous activities with cortical neurons during the learning. To study fear-related synaptic plasticity in the cortex and its functional connectivity with neurons in the amygdala and hippocampus will help us understand brain mechanisms of fear and improve clinical treatment of emotional disorders in patients.

scholarly journals Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Myeounghoon Cha ◽  
Songyeon Choi ◽  
Kyeongmin Kim ◽  
Bae Hwan Lee
Keyword(s):  
Chronic Pain ◽  
Nerve Injury ◽  
Pain Perception ◽  
Imaging Techniques ◽  
Insular Cortex ◽  
Pain Modulation ◽  
Anterior Cingulate ◽  
Related Area ◽  
Mtor Inhibition ◽  
The Brain

AbstractNeuropathic pain induced by a nerve injury can lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in chronic pain models are difficult to represent with functional imaging techniques, advances in manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) could facilitate the visualization of the activation of pain-specific neural responses in the cerebral cortex. In order to investigate the alleviation of pain nociception by mammalian target of rapamycin (mTOR) modulation, we observed cerebrocortical excitability changes and compared regional Mn2+ enhancement after mTOR inhibition. At day 7 after nerve injury, drugs were applied into the intracortical area, and drug (Vehicle, Torin1, and XL388) effects were compared within groups using MEMRI. Therein, signal intensities of the insular cortex (IC), primary somatosensory cortex of the hind limb region, motor cortex 1/2, and anterior cingulate cortex regions were significantly reduced after application of mTOR inhibitors (Torin1 and XL388). Furthermore, rostral-caudal analysis of the IC indicated that the rostral region of the IC was more strongly associated with pain perception than the caudal region. Our data suggest that MEMRI can depict pain-related signal changes in the brain and that mTOR inhibition is closely correlated with pain modulation in chronic pain rats.

scholarly journals Manganese-enhanced MRI depicts a reduction in brain response to nociception upon mTOR inhibition in chronic pain rats

2020 ◽  
Author(s):  
Myeounghoon Cha ◽  
Songyeon Choi ◽  
Kyeongmin Kim ◽  
Bae Hwan Lee
Keyword(s):  
Chronic Pain ◽  
Nerve Injury ◽  
Pain Perception ◽  
Imaging Techniques ◽  
Pain Modulation ◽  
Anterior Cingulate ◽  
Brain Response ◽  
Related Area ◽  
Mtor Inhibition ◽  
The Brain

Abstract Neuropathic pain induced by a nerve injury can lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in chronic pain models are difficult to represent with functional imaging techniques, advances in manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) could facilitate the visualization of the activation of pain-specific neural responses in the cerebral cortex. In order to investigate the alleviation of pain nociception by mammalian target of rapamycin (mTOR) modulation, we observed cerebrocortical excitability changes and compared regional Mn 2+ enhancement after mTOR inhibition. At day 7 after nerve injury, drugs were applied into the intracortical area, and drug (Vehicle, Torin1, and XL388) effects were compared within groups using MEMRI. Therein, signal intensities of the insular cortex (IC), primary somatosensory cortex of the hind limb region, motor cortex 1/2, and anterior cingulate cortex regions were significantly reduced after application of mTOR inhibitors (Torin1 and XL388). Furthermore, rostral-caudal analysis of the IC indicated that the rostral region of the IC was more strongly associated with pain perception than the caudal region. Our data suggest that MEMRI can depict pain-related signal changes in the brain and that mTOR inhibition is closely correlated with pain modulation in chronic pain rats.

scholarly journals Emotional memory and psychopathology

1997 ◽  
Vol 352 (1362) ◽  
pp. 1719-1726 ◽  
Author(s):  
◽  
Joseph E. Ledoux ◽  
Jeff Muller
Keyword(s):  
Fear Conditioning ◽  
Emotional Disorders ◽  
Sensory Information ◽  
Emotional Memory ◽  
Neural System ◽  
Central Nucleus ◽  
Cellular Mechanisms ◽  
Lateral Nucleus ◽  
Specific Fear ◽  
The Brain

A leading model for studying how the brain forms memories about unpleasant experiences is fear conditioning. A cumulative body of work has identified major components of the neural system mediating this form of learning. The pathways involve transmission of sensory information from processing areas in the thalamus and cortex to the amygdala. The amygdala's lateral nucleus receives and integrates the sensory inputs from the thalamic and cortical areas, and the central nucleus provides the interface with motor systems controlling specific fear responses in various modalities (behavioural, autonomic, endocrine). Internal connections within the amygdala allow the lateral and central nuclei to communicate. Recent studies have begun to identify some sites of plasticity in the circuitry and the cellular mechanisms involved in fear conditioning. Through studies of fear conditioning, our understanding of emotional memory is being taken to the level of cells and synapses in the brain. Advances in understanding emotional memory hold out the possibility that emotional disorders may be better defined and treatment improved.

Shared Brain Synaptic Mechanisms of Pain and Anxiety

2020 ◽  
pp. 50-62
Author(s):  
Ipek Yalcin ◽  
Min Zhuo
Keyword(s):  
Chronic Pain ◽  
Depressive Disorders ◽  
Pain Perception ◽  
Behavioral Sensitization ◽  
Long Term Potentiation ◽  
Anterior Cingulate ◽  
Cellular Mechanisms ◽  
Clinical Investigations ◽  
Term Potentiation ◽  
Monoaminergic System

Uncontrolled and persistent pain strongly associates with anxiety and depressive disorders and is the most common cause of disability impairing quality of life. In the past decade, a growing number of studies have focused on chronic pain comorbidities, aiming at modeling them and at understanding the pathophysiology of chronic and mood disorder comorbidity. These studies offer a unique opportunity to test cellular and molecular hypotheses, whereas human clinical investigations provide critical neuroanatomical insights, particularly through functional imaging studies. Altogether, the results point out that there are shared neural mechanisms between chronic pain and anxiety/depression, such as shared neuroanatomical substrates, changes in monoaminergic system, and neuroimmune and neuroendocrine responses. Based on recent studies, chronic anxiety triggered by chronic pain is mediated through presynaptic long-term potentiation (LTP) in the anterior cingulate cortex (ACC), a key cortical region for pain perception. Conversely, N-methyl-d-aspartate (NMDA) receptor–dependent postsynaptic LTP plays a more important role in behavioral sensitization in chronic pain. Thus, postsynaptic and presynaptic LTP in ACC neurons are likely the key cellular mechanisms for causing chronic pain and its associated anxiety, respectively.

scholarly journals Manganese-enhanced MRI depicts a reduction in brain response to nociception by mTOR inhibition in chronic pain rats

2020 ◽  
Author(s):  
Myeounghoon Cha ◽  
Songyeon Choi ◽  
Kyeongmin Kim ◽  
Bae Hwan Lee
Keyword(s):  
Chronic Pain ◽  
Nerve Injury ◽  
Pain Perception ◽  
Imaging Techniques ◽  
Pain Modulation ◽  
Anterior Cingulate ◽  
Brain Response ◽  
Related Area ◽  
Mtor Inhibition ◽  
The Brain

Abstract Neuropathic pain induced by a nerve injury could lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in the chronic pain model were difficult to represent with functional imaging techniques, advances in manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) could facilitate the visualization of the activation of pain-specific neural responses in the cerebral cortex. In order to investigate the alleviation of pain nociception by mammalian target of rapamycin (mTOR) modulation, we observed the cerebrocortical excitability changes and compared the regional Mn 2+ enhancement after mTOR inhibitions. At day 7 after nerve injury, drugs were applied into the intracortical area, and drug (Vehicle, Torin1 and XL388) effects were compared within groups using MEMRI. In the results, signal intensities of the insular cortex (IC), primary somatosensory cortex of the hind limb region (S1HL), motor cortex 1/2 (M1/2), and anterior cingulate cortex (ACC) regions were significantly reduced after application of mTOR inhibitors (Torin1 and XL388). Furthermore, the rostral-caudal analysis of the IC indicated that the rostral region of the IC was more associated with pain perception than caudal region. Our data suggest that MEMRI could present the pain-related signal changes in the brain, and mTOR inhibition is closely correlated with pain modulation in chronic pain rats.

scholarly journals The Cerebral Localization of Pain: Anatomical and Functional Considerations for Targeted Electrical Therapies

2020 ◽  
Vol 9 (6) ◽  
pp. 1945 ◽  
Author(s):  
Rose M. Caston ◽  
Elliot H. Smith ◽  
Tyler S. Davis ◽  
John D. Rolston
Keyword(s):  
United States ◽  
Chronic Pain ◽  
Electrical Stimulation ◽  
Brain Stimulation ◽  
Pain Perception ◽  
The United States ◽  
Anterior Cingulate ◽  
History Of ◽  
The Brain ◽  
Stimulation Of

Millions of people in the United States are affected by chronic pain, and the financial cost of pain treatment is weighing on the healthcare system. In some cases, current pharmacological treatments may do more harm than good, as with the United States opioid crisis. Direct electrical stimulation of the brain is one potential non-pharmacological treatment with a long history of investigation. Yet brain stimulation has been far less successful than peripheral or spinal cord stimulation, perhaps because of our limited understanding of the neural circuits involved in pain perception. In this paper, we review the history of using electrical stimulation of the brain to treat pain, as well as contemporary studies identifying the structures involved in pain networks, such as the thalamus, insula, and anterior cingulate. We propose that the thermal grill illusion, an experimental pain model, can facilitate further investigation of these structures. Pairing this model with intracranial recording will provide insight toward disentangling the neural correlates from the described anatomic areas. Finally, the possibility of altering pain perception with brain stimulation in these regions could be highly informative for the development of novel brain stimulation therapies for chronic pain.

Neurotransmitter systems of female mouse brain during growth of malignant melanoma modeled on the background of chronic pain

2018 ◽  
pp. 49-55
Author(s):  
О.И. Кит ◽  
И.М. Котиева ◽  
Е.М. Франциянц ◽  
И.В. Каплиева ◽  
Л.К. Трепитаки ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Cerebral Cortex ◽  
Malignant Melanoma ◽  
Sciatic Nerve ◽  
Female Mouse ◽  
Combined Effects ◽  
Malignant Growth ◽  
Course Of Disease ◽  
The Brain ◽  
Melanoma Growth

Известно, что биогенные амины (БА) участвуют в злокачественном росте, их уровень изменяется в ЦНС при болевом воздействии, однако исследований о сочетанном влиянии хронической боли (ХБ) и онкопатологии на динамику БА в головном мозге не проводилось. Цель: изучить особенности баланса БА в коре головного мозга в динамике роста меланомы, воспроизведенной на фоне ХБ. Материалы и методы. Работа выполнена на 64 мышах-самках, весом 21-22 г. Животным основной группы меланому В16/F10 перевивали под кожу спины через 2 недели после перевязки седалищных нервов. Группой сравнения служили мыши с меланомой без боли. Уровни БА: адреналина, норадреналина, дофамина (ДА), серотонина (5-НТ), гистамина, а также 5-ОИУК определяли методом иммуноферментного анализа. Результаты. У мышей с ХБ уменьшается содержание большинства БА, однако уровень ДА не изменяется. Метаболизм 5-НТ происходит с участием МАО. Развитие меланомы сопровождается увеличением содержания ДА и 5-НТ, тогда как МАО - ингибируется. Направленность сдвигов БА при развитии меланомы на фоне ХБ оказалась практически такой же, как и без неё. В то же время ХБ ограничивает накопление 5-НТ в коре мозга при меланоме, что сопровождается более агрессивным её течением. Выводы. ХБ ограничивает включение стресс-лимитирующих механизмов в головном мозге при развитии меланомы у мышей, что приводит к более агрессивному течению злокачественного процесса. Biogenic amines (BA) are known to be involved in malignant growth, and their CNS levels change in pain; however, there are no studies of combined effects of chronic pain (CP) and cancer on BA dynamics in the brain. Aim: To study features of BA balance in the cerebral cortex during melanoma growth associated with CP. Material and methods. The study included 64 female mice weighing 21-22 g. In the main groups, B16/F10 melanoma was transplanted under the skin of the back two weeks following sciatic nerve ligation. Mice with melanoma without pain were used as the control. Concentrations of BA: adrenaline, noradrenaline, dopamine (DA), serotonin (5-HT), histamine and 5-HIAA were measured with ELISA. Results. Concentrations of BAs decreased in mice with CP although DA levels did not change. 5-HT metabolism involved MAO. The development of melanoma was accompanied by increases in DA and 5-HT whereas MAO was inhibited. The direction of BA changes during the development of melanoma was the same with and without CP. At the same time, CP with melanoma limited accumulation of 5-HT in the cerebral cortex, which resulted in even more aggressive course of cancer. Conclusion. CP restricted the activation of cerebral stress-limiting mechanisms during the development of melanoma in mice, which resulted in a more aggressive course of disease.

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