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 Long-term potentiation in the anterior cingulate cortex and chronic pain

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130146 ◽  
Author(s):  
Min Zhuo
Keyword(s):  
Chronic Pain ◽  
Anterior Cingulate Cortex ◽  
Dorsal Horn ◽  
Glutamate Release ◽  
Cingulate Cortex ◽  
Long Term Potentiation ◽  
Anterior Cingulate ◽  
Spinal Cord Dorsal Horn ◽  
Term Potentiation

Glutamate is the primary excitatory transmitter of sensory transmission and perception in the central nervous system. Painful or noxious stimuli from the periphery ‘teach’ humans and animals to avoid potentially dangerous objects or environments, whereas tissue injury itself causes unnecessary chronic pain that can even last for long periods of time. Conventional pain medicines often fail to control chronic pain. Recent neurobiological studies suggest that synaptic plasticity taking place in sensory pathways, from spinal dorsal horn to cortical areas, contributes to chronic pain. Injuries trigger long-term potentiation of synaptic transmission in the spinal cord dorsal horn and anterior cingulate cortex, and such persistent potentiation does not require continuous neuronal activity from the periphery. At the synaptic level, potentiation of excitatory transmission caused by injuries may be mediated by the enhancement of glutamate release from presynaptic terminals and potentiated postsynaptic responses of AMPA receptors. Preventing, ‘erasing’ or reducing such potentiation may serve as a new mechanism to inhibit chronic pain in patients in the future.

scholarly journals Preoperative anxiety induces chronic postoperative pain by activating astrocytes in the anterior cingulate cortex region

2019 ◽  
Vol 65 (9) ◽  
pp. 1174-1180 ◽  
Author(s):  
Damin Gu ◽  
Minmin Zhou ◽  
Chao Han ◽  
Daoyun Lei ◽  
Songhui Xie ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Postoperative Pain ◽  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Long Term Potentiation ◽  
Preoperative Anxiety ◽  
Anterior Cingulate ◽  
Chronic Postoperative Pain ◽  
Term Potentiation ◽  
Mechanical Thresholds

SUMMARY OBJECTIVE The study aims to explore the relationship between preoperative anxiety and chronic postoperative pain. METHODS A total of forty rats were divided into four groups, control, single-prolonged stress alone, Hysterectomy alone, and SPS+ Hysterectomy. The paw withdrawal mechanical thresholds (PWMT) were examined. qRT-PCR and western blotting assay were performed to detect the GFAP expression in astrocytes isolated from the anterior cingulate cortex (ACC) region. In addition, the long-term potentiation (LTP) in ACC was examined. RESULTS Rats in the SPS group or the Hysterectomy alone group had no significant effect on chronic pain formation, but SPS can significantly induce chronic pain after surgery. Astrocytes were still active, and the LTP was significantly increased three days after modeling in the SPS+Hysterectomy group. CONCLUSIONS anxiety can induce chronic pain by activating astrocytes in the ACC region.

Psychophysical Evidence for Long-Term Potentiation of C-Fiber and Aδ-Fiber Pathways in Humans by Analysis of Pain Descriptors

2007 ◽  
Vol 97 (3) ◽  
pp. 2559-2563 ◽  
Author(s):  
Niels Hansen ◽  
Thomas Klein ◽  
Walter Magerl ◽  
Rolf-Detlef Treede
Keyword(s):  
Pain Perception ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Burning Pain ◽  
Term Potentiation ◽  
C Fiber ◽  
Pain Ratings ◽  
Two Factors ◽  
Pain Descriptors

Long-term potentiation of human pain perception (nociceptive LTP) to single electrical test stimuli was induced by high-frequency stimulation (HFS) of cutaneous nociceptive afferents. Numerical pain ratings and a list of sensory pain descriptors disclosed the same magnitude of nociceptive LTP (23% increase for >60 min, P < 0.001), whereas affective pain descriptors were not significantly enhanced. Factor analysis of the sensory pain descriptors showed that facilitation was restricted to two factors characterized by hot and burning (+41%) and piercing and stinging (+21%, both P < 0.01), whereas a factor represented by throbbing and beating was not significantly increased (+9%, P = 0.47). The increased perception of the burning pain quality for >1 h after HFS is interpreted as a LTP-like facilitation of the conditioned cutaneous C-fiber pathway. Additionally, the increase of the stinging pain quality supplied evidence for facilitation of a sharpness-sensitive Aδ-fiber pathway.

scholarly journals Plasticity-Related PKMζSignaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jeongsoo Han ◽  
Minjee Kwon ◽  
Myeounghoon Cha ◽  
Motomasa Tanioka ◽  
Seong-Karp Hong ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Neural Plasticity ◽  
Mechanical Allodynia ◽  
Insular Cortex ◽  
Long Term Potentiation ◽  
Inhibitory Peptide ◽  
Term Potentiation ◽  
Potential Applications

The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ(PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζin the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. Afterζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ(p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζwere decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζand that ZIP has potential applications for relieving chronic pain.

scholarly journals Presynaptic long-term potentiation requires extracellular signal-regulated kinases in the anterior cingulate cortex

2020 ◽  
Vol 16 ◽  
pp. 174480692091724
Author(s):  
Qi-Yu Chen ◽  
Zhi-Ling Zhang ◽  
Qin Liu ◽  
Chao-Jun Chen ◽  
Xiao-Kang Zhang ◽  
...  
Keyword(s):  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Long Term Potentiation ◽  
Anterior Cingulate ◽  
Term Potentiation ◽  
Extracellular Signal

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.

Remodeling the Plasticity Debate: The Presynaptic Locus Revisited

Physiology ◽  
2006 ◽  
Vol 21 (5) ◽  
pp. 346-351 ◽  
Author(s):  
Stefan Krueger ◽  
Reiko Maki Fitzsimonds
Keyword(s):  
Long Term Potentiation ◽  
Glutamatergic Synapses ◽  
Cellular Mechanisms ◽  
Present Evidence ◽  
Term Potentiation

The cellular mechanisms contributing to long-term potentiation and activity-induced formation of glutamatergic synapses have been intensely debated. Recent studies have sparked renewed interest in the role of presynaptic components in these processes. Based on the present evidence, it appears likely that long-term plasticity utilizes both pre- and postsynaptic expression mechanisms.

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.

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