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 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 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 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.

scholarly journals Characterization of New TRPM8 Modulators in Pain Perception

2019 ◽  
Vol 20 (22) ◽  
pp. 5544 ◽  
Author(s):  
Carmen De Caro ◽  
Claudia Cristiano ◽  
Carmen Avagliano ◽  
Alessia Bertamino ◽  
Carmine Ostacolo ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Pain Perception ◽  
Transient Receptor Potential ◽  
Pain Modulation ◽  
The Body ◽  
Sprague Dawley ◽  
Transient Receptor Potential Melastatin ◽  
Pain Models ◽  
Excessive Activation

Background: Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to reduce acute and chronic pain, it is also reported that TRPM8 activation produces analgesia. These conflicting results could be explained by extracellular Ca2+-dependent desensitization that is induced by an excessive activation. Likely, this effect is due to phosphatidylinositol 4,5-bisphosphate (PIP2) depletion that leads to modification of TRPM8 channel activity, shifting voltage dependence towards more positive potentials. This phenomenon needs further evaluation and confirmation that would allow us to understand better the role of this channel and to develop new therapeutic strategies for controlling pain. Experimental approach: To understand the role of TRPM8 in pain perception, we tested two specific TRPM8-modulating compounds, an antagonist (IGM-18) and an agonist (IGM-5), in either acute or chronic animal pain models using male Sprague-Dawley rats or CD1 mice, after systemic or topical routes of administration. Results: IGM-18 and IGM-5 were fully characterized in vivo. The wet-dog shake test and the body temperature measurements highlighted the antagonist activity of IGM-18 on TRPM8 channels. Moreover, IGM-18 exerted an analgesic effect on formalin-induced orofacial pain and chronic constriction injury-induced neuropathic pain, demonstrating the involvement of TRPM8 channels in these two pain models. Finally, the results were consistent with TRPM8 downregulation by agonist IGM-5, due to its excessive activation. Conclusions: TRPM8 channels are strongly involved in pain modulation, and their selective antagonist is able to reduce both acute and chronic pain.

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.

EMDR in the Treatment of Chronic Pain

2009 ◽  
Vol 3 (2) ◽  
pp. 66-79 ◽  
Author(s):  
Alexandra Mazzola ◽  
Marìa Lujàn Calcagno ◽  
Marìa Teresa Goicochea ◽  
Honorio Pueyrredòn ◽  
Jorge Leston ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sleep Disturbances ◽  
Pain Perception ◽  
Psychological Treatment ◽  
Life Quality ◽  
Outcome Evaluation ◽  
Pain Modulation ◽  
Depression Level ◽  
Objective Outcome

Chronic pain can significantly diminish life quality, causing depression, anxiety, and sleep disturbances, and may lead to neuroplastic processes that influence pain modulation. The current study investigated eye movement desensitization and reprocessing (EMDR) treatment of 38 patients suffering from chronic pain with 12 weekly 90-minute sessions. A battery of self-reported questionnaires assessing quality of life, pain intensity, and depression level were administered pre- and posttreatment for objective outcome evaluation. The Structured Clinical Interview for DSM was administered at pretreatment to identify participants’ personality traits that may influence pain perception. Patients showed statistically significant improvement relative to baseline after 12 weeks of EMDR treatment. Our findings suggest that EMDR is an effective tool in the psychological treatment of chronic pain, resulting in decrease pain sensations, pain-related negative affect, and anxiety and depression levels. We examine possible theories about the mechanisms by which EMDR achieves these effects. Results were consistent with the underlying EMDR premise that posits the important effect of emotions on pain perception.

scholarly journals The Transition from Acute to Chronic Pain: Dynamic Epigenetic Reprogramming of the Mouse Prefrontal Cortex up to One Year Following Nerve Injury

2020 ◽  
Author(s):  
Lucas Topham ◽  
Stephanie Gregoire ◽  
HyungMo Kang ◽  
Mali Salmon-Divon ◽  
Elad Lax ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chronic Pain ◽  
Prefrontal Cortex ◽  
Nerve Injury ◽  
Acute Pain ◽  
Dna Sequences ◽  
Pain Modulation ◽  
Epigenetic Reprogramming ◽  
Time Points ◽  
Differentially Methylated Genes

AbstractChronic pain is associated with persistent structural and functional changes throughout the neuroaxis, including in the prefrontal cortex (PFC). The PFC is important in the integration of sensory, cognitive and emotional information and in conditioned pain modulation. We previously reported wide-spread epigenetic reprogramming in the PFC many months following nerve injury in rodents. Epigenetic modifications, including DNA methylation, can drive changes in gene expression without modifying DNA sequences. To date, little is known about epigenetic dysregulation at the onset of acute pain or how it progresses as pain transitions from acute to chronic. We hypothesize that acute pain following injury results in rapid and persistent epigenetic remodelling in the PFC that evolves as pain becomes chronic. We further propose that understanding epigenetic remodelling will provide insights into the mechanisms driving pain-related changes in the brain. Epigenome-wide analysis was performed in the mouse PFC 1 day, 2 weeks, 6 months, and 1 year following peripheral injury using the spared nerve injury (SNI) in mice. SNI resulted in rapid and persistent changes in DNA methylation, with robust differential methylation observed between SNI and sham-operated control mice at all time points. Hundreds of differentially methylated genes were identified, including many with known function in pain. Pathway analysis revealed enrichment in genes related to stimulus response at early time points, immune function at later time points and actin and cytoskeletal regulation throughout the time course. Increased attention to pain chronicity as a factor is recommended for both pain research and management.

scholarly journals Role of Descending Dopaminergic Pathways in Pain Modulation

2019 ◽  
Vol 17 (12) ◽  
pp. 1176-1182 ◽  
Author(s):  
Changsheng Li ◽  
Sufang Liu ◽  
Xihua Lu ◽  
Feng Tao
Keyword(s):  
Chronic Pain ◽  
Well Being ◽  
Pain Modulation ◽  
Central Regulation ◽  
Dopaminergic Systems ◽  
Different Types ◽  
Dopaminergic Pathways ◽  
The Brain

Pain, especially when chronic, is a common reason patients seek medical care and it affects the quality of life and well-being of the patients. Unfortunately, currently available therapies for chronic pain are often inadequate because the neurobiological basis of such pain is still not fully understood. Although dopamine has been known as a neurotransmitter to mediate reward and motivation, accumulating evidence has shown that dopamine systems in the brain are also involved in the central regulation of chronic pain. Most importantly, descending dopaminergic pathways play an important role in pain modulation. In this review, we discuss dopamine receptors, dopaminergic systems in the brain, and the role of descending dopaminergic pathways in the modulation of different types of pain.

Neurobiology of Acute and Chronic Pain

2019 ◽  
pp. 111-122
Author(s):  
Adrian Pichurko ◽  
Richard E. Harris
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Pain Perception ◽  
Conscious Experience ◽  
Initial Point ◽  
Neurosurgical Procedures ◽  
Evidence Based Treatments ◽  
Nuanced Understanding ◽  
Chronic Pain Conditions ◽  
The Brain

Pain is a complex phenomenon that may involve both peripheral and central neurobiological processes. Nociception is the unconscious registration of a noxious stimulus by the nervous system, while pain is a conscious experience. Neurobiological correlates of pain perception have been characterized from the initial point of tissue damage to its realization in the brain. Importantly, various pharmacological and psychological interventions exist that can target various points along this pathway. Evidence shows the nervous system remodels in response to chronic pain. More evidence-based treatments showing efficacy for chronic pain conditions are needed. Finally, an individualized and multidisciplinary approach in concordance with the biopsychosocial model of illness is often advocated. The neuroanaesthetist requires a nuanced understanding of pain, since many patients presenting for neurosurgical procedures suffer chronic pain.

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