scholarly journals Differential Rearrangement of Excitatory Inputs to the Medial Prefrontal Cortex in Chronic Pain Models

2021 ◽  
Vol 15 ◽  
Author(s):  
Taylor Jefferson ◽  
Crystle J. Kelly ◽  
Marco Martina
Keyword(s):  
Chronic Pain ◽  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Sleep Disturbances ◽  
Sensory Information ◽  
Excitatory Input ◽  
Pain Models ◽  
Circuit Components ◽  
Information Streams

Chronic pain patients suffer a disrupted quality of life not only from the experience of pain itself, but also from comorbid symptoms such as depression, anxiety, cognitive impairment, and sleep disturbances. The heterogeneity of these symptoms support the idea of a major involvement of the cerebral cortex in the chronic pain condition. Accordingly, abundant evidence shows that in chronic pain the activity of the medial prefrontal cortex (mPFC), a brain region that is critical for executive function and working memory, is severely impaired. Excitability of the mPFC depends on the integrated effects of intrinsic excitability and excitatory and inhibitory inputs. The main extracortical sources of excitatory input to the mPFC originate in the thalamus, hippocampus, and amygdala, which allow the mPFC to integrate multiple information streams necessary for cognitive control of pain including sensory information, context, and emotional salience. Recent techniques, such as optogenetic methods of circuit dissection, have made it possible to tease apart the contributions of individual circuit components. Here we review the synaptic properties of these main glutamatergic inputs to the rodent mPFC, how each is altered in animal models of chronic pain, and how these alterations contribute to pain-associated mPFC deactivation. By understanding the contributions of these individual circuit components, we strive to understand the broad spectrum of chronic pain and comorbid pathologies, how they are generated, and how they might be alleviated.

Sleep disturbance in patients attending specialized chronic pain clinics in Denmark: a longitudinal study examining the relationship between sleep and pain outcomes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Henrik Bjarke Vaegter ◽  
Mette Terp Høybye ◽  
Frederik Hjorth Bergen ◽  
Christine E. Parsons
Keyword(s):  
Quality Of Life ◽  
Chronic Pain ◽  
Sleep Quality ◽  
Pain Intensity ◽  
Sleep Disturbances ◽  
Pain Disability ◽  
Pain Clinics ◽  
Pain Outcomes

Abstract Objectives Sleep disturbances are highly prevalent in patients with chronic pain. However, the majority of studies to date examining sleep disturbances in patients with chronic pain have been population-based cross-sectional studies. The aims of this study were to 1) examine the frequency of sleep disturbances in patients referred to two interdisciplinary chronic pain clinics in Denmark, 2) explore associations between sleep disturbances and pain intensity, disability and quality of life at baseline and follow-up, and 3) explore whether changes in sleep quality mediated the relationships between pain outcomes at baseline and pain outcomes at follow-up. Methods We carried out a longitudinal observational study, examining patients enrolled in two chronic pain clinics assessed at baseline (n=2,531) and post-treatment follow-up (n=657). Patients reported on their sleep disturbances using the sleep quality subscale of the Karolinska Sleep Questionnaire (KSQ), their pain intensity using 0–10 numerical rating scales, their pain-related disability using the Pain Disability Index (PDI), and quality of life using the EuroQol-VAS scale. The average time between baseline and follow-up was 207 days (SD=154). Results At baseline, the majority of patients reported frequent sleep disturbances. We found a significant association at baseline between self-reported sleep disturbances and pain intensity, pain-related disability, and quality of life, where greater sleep disturbance was associated with poorer outcomes. At follow-up, patients reported significant improvements across all pain and sleep outcomes. In two mediation models, we showed that changes in sleep disturbances from baseline to follow-up were significantly associated with (i) pain intensity at follow-up, and (ii) pain disability at follow-up. However, baseline pain intensity and disability scores were not associated with changes in sleep disturbances and, we did not find evidence for significant mediation of either pain outcome by changes in sleep disturbances. Conclusions Self-reported sleep disturbances were associated with pain outcomes at baseline and follow-up, with greater sleep disturbances associated with poorer pain outcomes. Changes in sleep quality did not mediate the relationships between baseline and follow-up scores for pain intensity and disability. These findings contribute to a growing body of evidence confirming an association between sleep and chronic pain experience, particularly suggestive of a sleep to pain link. Our data following patients after interdisciplinary treatment suggests that improved sleep is a marker for a better outcome after treatment.

scholarly journals The claustrum-medial prefrontal cortex network controls attentional set-shifting

2020 ◽  
Author(s):  
Leon Fodoulian ◽  
Olivier Gschwend ◽  
Chieko Huber ◽  
Sophie Mutel ◽  
Rodrigo F. Salazar ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Cognitive Deficits ◽  
Pyramidal Cells ◽  
Excitatory Input ◽  
Set Shifting ◽  
Attentional Set ◽  
Attentional Set Shifting ◽  
Reciprocal Connections

SUMMARYIn various mental disorders, dysfunction of the prefrontal cortex contributes to cognitive deficits. Here we studied how the claustrum (CLA), a nucleus sharing reciprocal connections with the cortex, may participate in these cognitive impairments. We show that specific ensembles of CLA and of medial prefrontal cortex (mPFC) neurons are activated during a task requiring cognitive control such as attentional set-shifting, i.e. the ability to shift attention towards newly relevant stimulus-reward associations while disengaging from irrelevant ones. CLA neurons exert a direct excitatory input on mPFC pyramidal cells, and chemogenetic inhibition of CLA neurons suppresses the formation of specific mPFC assemblies during attentional set-shifting. Furthermore, impairing the recruitment of specific CLA assemblies through opto/chemogenetic manipulations prevents attentional set-shifting. In conclusion, we propose that the CLA controls the reorganization of mPFC ensembles to enable attentional set-shifting, emphasizing a potential role of the CLA-mPFC network in attentional dysfunctions.

scholarly journals Reduced Glutamate in the Medial Prefrontal Cortex Is Associated With Emotional and Cognitive Dysregulation in People With Chronic Pain

2019 ◽  
Vol 10 ◽  
Author(s):  
Brooke Naylor ◽  
Negin Hesam-Shariati ◽  
James H. McAuley ◽  
Simon Boag ◽  
Toby Newton-John ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex

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.

Disruption to normal excitatory and inhibitory function within the medial prefrontal cortex in people with chronic pain

2021 ◽  
Author(s):  
David Kang ◽  
Negin Hesam‐Shariati ◽  
James H. McAuley ◽  
Monzurul Alam ◽  
Zina Trost ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Inhibitory Function

scholarly journals Context-invariant neural dynamics underlying the encoding of Bayesian uncertainty, but not confidence

2019 ◽  
Author(s):  
Vincenzo G. Fiore ◽  
Xiaosi Gu
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Effective Connectivity ◽  
Sensory Information ◽  
Anterior Insula ◽  
Anterior Cingulate ◽  
Neural Dynamics ◽  
Network Computing ◽  
Evidence Accumulation ◽  
Healthy Humans

AbstractBeliefs about action-outcomes contingencies are often updated in opaque environments where feedbacks might be inaccessible and agents might need to rely on other information for evidence accumulation. It remains unclear, however, whether and how the neural dynamics subserving confidence and uncertainty during belief updating might be context-dependent. Here, we applied a Bayesian model to estimate uncertainty and confidence in healthy humans (n=28) using two multi-option fMRI tasks, one with and one without feedbacks. We found that across both tasks, uncertainty was computed in the anterior insular, anterior cingulate, and dorsolateral prefrontal cortices, whereas confidence was encoded in anterior hippocampus, amygdala and medial prefrontal cortex. However, dynamic causal modelling (DCM) revealed a critical divergence between how effective connectivity in these networks was modulated by the available information. Specifically, there was directional influence from the anterior insula to other regions during uncertainty encoding, independent of outcome availability. Conversely, the network computing confidence was driven either by the anterior hippocampus when outcomes were not available, or by the medial prefrontal cortex and amygdala when feedbacks were immediately accessible. These findings indicate that confidence encoding might largely rely on evidence accumulation and therefore dynamically changes as a function of the available sensory information (i.e. symbolic sequences monitored by the hippocampus, and monetary feedbacks computed by amygdala and medial prefrontal cortex). In contrast, uncertainty could be triggered by any information that disputes existing beliefs (i.e. processed in the insula), independent of its content.Significance StatementOur choices are guided by our beliefs about action-outcome contingencies. In environments where only one action leads to a desired outcome, high estimated action-outcome probabilities result in confidence, whereas low probabilities distributed across multiple choices result in uncertainty. These estimations are continuously updated, sometimes based on feedbacks provided by the environment, but sometimes this update takes place in opaque environments where feedbacks are not readily available. Here, we show that uncertainty computations are driven by the anterior insula, independent of feedback availability. Conversely, confidence encoding dynamically adapts to the information available, as we found it was driven either by the anterior hippocampus, when feedback was absent, or by the medial prefrontal cortex and amygdala, otherwise.

scholarly journals Insula to mPFC reciprocal connectivity differentially underlies novel taste neophobic response and learning

2021 ◽  
Author(s):  
Haneen Kayyal ◽  
Sailendrakumar Kolatt Chandran ◽  
Adonis Yiannakas ◽  
Nathaniel Gould ◽  
Mohammad Khamaisy ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Sensory Information ◽  
Insular Cortex ◽  
Memory Formation ◽  
Intrinsic Properties ◽  
Insight Into ◽  
Taste Experience ◽  
Neophobic Response

To survive in an ever-changing environment, animals must detect and learn salient information. The anterior insular cortex (aIC) and medial prefrontal cortex (mPFC) are heavily implicated in salience and novelty processing, and specifically, the processing of taste sensory information. Here, we examined the role of aIC-mPFC reciprocal connectivity in novel taste neophobia and memory formation, in mice. Using pERK and neuronal intrinsic properties as markers for neuronal activation, and retrograde AAV (rAAV) constructs for connectivity, we demonstrate a correlation between aIC-mPFC activity and novel taste experience. Furthermore, by expressing inhibitory chemogenetic receptors in these projections, we show that aIC-to-mPFC activity is necessary for both taste neophobia and its attenuation. However, activity within mPFC-to-aIC projections is essential only for the neophobic reaction but not for the learning process. These results provide an insight into the cortical circuitry needed to detect, react to- and learn salient stimuli, a process critically involved in psychiatric disorders.

Duloxetine Added to Tramadol in Chronic Pain Syndrome

2016 ◽  
Vol 33 (S1) ◽  
pp. S500-S501
Author(s):  
M. Domijan ◽  
Z. Lončar ◽  
S. Udovičić
Keyword(s):  
Quality Of Life ◽  
Chronic Pain ◽  
Sleep Disturbances ◽  
Short Form ◽  
Pain Syndrome ◽  
Mcgill Pain Questionnaire ◽  
Chronic Pain Syndrome ◽  
Reduction Of Pain ◽  
Competing Interest

IntroductionAbout 15–20% of the population suffering from the chronic pain. Over time, chronic pain can result in different emotional problems, social isolation, sleep disturbances, which reduce the quality of life. Chronic pain syndrome (CPS) indicates persistent pain, subjective symptoms in excess of objective findings, associated dysfunctional pain behavious and self-limitation in activities of daily living. Duloxetine is a potent antidepressant approved by the Food and Drug Administration for the chronic musculoskeletal disorder, diabetic neuropathic pain, fibromyalgia, generallized anxiety disorder and major depressive disorder.ObjectiveTo determine the effect of duloxetine on the reduction of pain and psychosocial suffering.AimsThe goal of the treatment should be to effectively reduce pain while improving function and reducing psychosocial suffering.MethodsThirty-six adult, nondepressed patients, already on tramadol therapy were included. Patients with VAS (visual analogue scale) ≥ 4were treated with duloxetine for 13 weeks. We measured pain intensity with the McGill Pain Questionnaire-Short Form (MPQ-SF) and compared VAS before starting the treatment with duloxetine and weekly for 13 weeks.ResultsPain response was defined as a 30%decrease in the MPQ-SF. A total of 62.5% of the sample met these criteria for response. Among them, 13.8% of patients were discontinued because of adverse effects. Duloxetine significantly improved functioning and the quality of life in patients with CPS.ConclusionsBecause of it is analgesic properties, duloxetine in the lower antidepressant doses (60 mg taken ones daily) combined with tramadol (another analgesic agent) can be useful in CPS for patients who do not respond satisfactory to monotherapy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals The Role of Mesostriatal Dopamine System and Corticostriatal Glutamatergic Transmission in Chronic Pain

2021 ◽  
Vol 11 (10) ◽  
pp. 1311
Author(s):  
Barbara Ziółkowska
Keyword(s):  
Chronic Pain ◽  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
D2 Receptor ◽  
Dorsal Striatum ◽  
Persistent Pain ◽  
Pain Modulation ◽  
Medium Spiny Neurons ◽  
Analgesic Effects

There is increasing recognition of the involvement of the nigrostriatal and mesolimbic dopamine systems in the modulation of chronic pain. The first part of the present article reviews the evidence indicating that dopamine exerts analgesic effects during persistent pain by stimulating the D2 receptors in the dorsal striatum and nucleus accumbens (NAc). Thereby, dopamine inhibits striatal output via the D2 receptor-expressing medium spiny neurons (D2-MSN). Dopaminergic neurotransmission in the mesostriatal pathways is hampered in chronic pain states and this alteration maintains and exacerbates pain. The second part of this article focuses on the glutamatergic inputs from the medial prefrontal cortex to the NAc, their activity changes in chronic pain, and their role in pain modulation. Finally, interactions between dopaminergic and glutamatergic inputs to the D2-MSN are considered in the context of persistent pain. Studies using novel techniques indicate that pain is regulated oppositely by two independent dopaminergic circuits linking separate parts of the ventral tegmental area and of the NAc, which also interact with distinct regions of the medial prefrontal cortex.

scholarly journals The Medial Prefrontal Cortex as a Central Hub for Mental Comorbidities Associated with Chronic Pain

2020 ◽  
Vol 21 (10) ◽  
pp. 3440 ◽  
Author(s):  
Kai K. Kummer ◽  
Miodrag Mitrić ◽  
Theodora Kalpachidou ◽  
Michaela Kress
Keyword(s):  
Chronic Pain ◽  
Prefrontal Cortex ◽  
Anterior Cingulate Cortex ◽  
Medial Prefrontal Cortex ◽  
Cingulate Cortex ◽  
Psychosocial Interventions ◽  
Anterior Cingulate ◽  
Fine Tuning ◽  
Mental Comorbidities ◽  
Local Circuitry

Chronic pain patients frequently develop and suffer from mental comorbidities such as depressive mood, impaired cognition, and other significant constraints of daily life, which can only insufficiently be overcome by medication. The emotional and cognitive components of pain are processed by the medial prefrontal cortex, which comprises the anterior cingulate cortex, the prelimbic, and the infralimbic cortex. All three subregions are significantly affected by chronic pain: magnetic resonance imaging has revealed gray matter loss in all these areas in chronic pain conditions. While the anterior cingulate cortex appears hyperactive, prelimbic, and infralimbic regions show reduced activity. The medial prefrontal cortex receives ascending, nociceptive input, but also exerts important top-down control of pain sensation: its projections are the main cortical input of the periaqueductal gray, which is part of the descending inhibitory pain control system at the spinal level. A multitude of neurotransmitter systems contributes to the fine-tuning of the local circuitry, of which cholinergic and GABAergic signaling are particularly emerging as relevant components of affective pain processing within the prefrontal cortex. Accordingly, factors such as distraction, positive mood, and anticipation of pain relief such as placebo can ameliorate pain by affecting mPFC function, making this cortical area a promising target region for medical as well as psychosocial interventions for pain therapy.

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