Cognitive Impairment in Pain through Amygdala-Driven Prefrontal Cortical Deactivation
TLDR
This study shows that the amygdala contributes not only to emotional-affective but also cognitive effects of pain, which has important implications for the understanding of amygdala functions and amygdalo-cortical interactions.Abstract:
Cognitive deficits such as impaired decision-making can be a consequence of persistent pain. Normal functions of the intact amygdala and prefrontal cortex are required for emotion-based decision-making that relies on the ability to assess risk, attribute value, and identify advantageous strategies. We tested the hypothesis that pain-related cognitive deficits result from amygdala-driven impairment of medial prefrontal cortical (mPFC) function. To do this, we used electrophysiological single-unit recordings in vivo, patch clamp in brain slices, and various behavioral assays to show that increased neuronal activity in the amygdala in an animal model of arthritis pain was accompanied by decreased mPFC activation and impaired decision-making. Furthermore, pharmacologic inhibition (with a corticotropin-releasing factor 1 receptor antagonist) of pain-related hyperactivity in the basolateral amygdala (BLA), but not central amygdala (CeA), reversed deactivation of mPFC pyramidal cells and improved decision-making deficits. Pain-related cortical deactivation resulted from a shift of balance between inhibitory and excitatory synaptic transmission. Direct excitatory transmission to mPFC pyramidal cells did not change in the pain model, whereas polysynaptic inhibitory transmission increased. GABAergic transmission was reduced by non-NMDA receptor antagonists, suggesting that synaptic inhibition was glutamate driven. The results are consistent with a model of BLA-driven feedforward inhibition of mPFC neurons. In contrast to the differential effects of BLA versus CeA hyperactivity on cortical-cognitive functions, both amygdala nuclei modulate emotional-affective pain behavior. Thus, this study shows that the amygdala contributes not only to emotional-affective but also cognitive effects of pain. The novel amygdalo-cortical pain mechanism has important implications for our understanding of amygdala functions and amygdalo-cortical interactions.read more
Citations
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Journal ArticleDOI
Cognitive and emotional control of pain and its disruption in chronic pain
TL;DR: The accumulating evidence that chronic pain itself alters brain circuitry, including that involved in endogenous pain control, is examined, suggesting that controlling pain becomes increasingly difficult as pain becomes chronic.
Journal ArticleDOI
The effect of pain on cognitive function: a review of clinical and preclinical research.
TL;DR: The anatomical, neurochemical and molecular substrates common to both cognitive processing and supraspinal pain processing are described, and the evidence for their involvement in pain-related cognitive impairment is presented.
Journal ArticleDOI
Pain and emotion: a biopsychosocial review of recent research.
Mark A. Lumley,Jay L. Cohen,Jay L. Cohen,George S. Borszcz,Annmarie Cano,Alison M. Radcliffe,Laura S. Porter,Howard Schubiner,Howard Schubiner,Francis J. Keefe +9 more
TL;DR: Empirical research documents the neural processes that distinguish affective from sensory pain dimensions, link emotion and pain, and generate central nervous system pain sensitization; and social research shows the potential importance of emotional communication, empathy, attachment, and rejection.
Journal ArticleDOI
Abnormalities in Hippocampal Functioning with Persistent Pain
Amelia A. Mutso,Daniel Radzicki,Marwan N. Baliki,Lejian Huang,Ghazal Banisadr,Maria Virginia Centeno,Jelena Radulovic,Marco Martina,Richard J. Miller,A. Vania Apkarian +9 more
TL;DR: The results indicate that hippocampus-mediated behavior, synaptic plasticity, and neurogenesis are abnormal in neuropathic rodents, and these abnormalities may underlie learning and emotional deficits commonly observed in chronic pain patients.
Journal ArticleDOI
Role of the Prefrontal Cortex in Pain Processing.
TL;DR: The medial PFC (mPFC) could serve dual, opposing roles in pain: it mediates antinociceptive effects, due to its connections with other cortical areas, and as the main source of cortical afferents to the PAG for modulation of pain.
References
More filters
Book
The Rat Brain in Stereotaxic Coordinates
George Paxinos,Charles Watson +1 more
TL;DR: This paper presents a meta-analyses of the determinants of earthquake-triggered landsliding in the Czech Republic over a period of 18 months in order to establish a probabilistic framework for estimating the intensity of the earthquake.
Journal ArticleDOI
Pharmacology and functions of metabotropic glutamate receptors.
TL;DR: The findings suggest that the mGluRs provide a novel target for development of therepeutic agents that could have a significant impact on neuropharmacology.
Journal ArticleDOI
A permanent change in brain function resulting from daily electrical stimulation.
TL;DR: High-intensity stimulation studies revealed that the development of convulsions was not based simply on threshold reduction, but involved complex reorganization of function.
Journal ArticleDOI
Interneurons of the neocortical inhibitory system.
TL;DR: This review focuses on the organizing principles that govern the diversity of inhibitory interneurons and their circuits.
Journal ArticleDOI
Contributions of the Amygdala to Emotion Processing: From Animal Models to Human Behavior
TL;DR: Five major research topics are highlighted that illustrate parallel roles for the amygdala in humans and other animals, including implicit emotional learning and memory, emotional modulation of memory,otional influences on attention and perception, emotion and social behavior, and emotion inhibition and regulation.