Pain and consciousness.
12 Oct 2017-Progress in Neuro-psychopharmacology & Biological Psychiatry (Prog Neuropsychopharmacol Biol Psychiatry)-Vol. 87, pp 193-199
TL;DR: It is contended that even in unconscious subjects, repeated limbic and vegetative activation by painful stimuli via spino‐amygdalar pathways can generate implicit memory traces and stimulus‐response abnormal sequences, possibly contributing to long‐standing anxiety or hyperalgesic syndromes in patients surviving coma.
Abstract: The aversive experience we call "pain" results from the coordinated activation of multiple brain areas, commonly described as a "pain matrix". This is not a fixed arrangement of structures but rather a fluid system composed of several interacting networks: A 'nociceptive matrix' includes regions receiving input from ascending nociceptive systems, and ensures the bodily characteristics of physical pain. A further set of structures receiving secondary input supports the 'salience' attributes of noxious stimuli, triggers top-down cognitive controls, and -most importantly- ensures the passage from pre-conscious nociception to conscious pain. Expectations and beliefs can still modulate the conscious experience via activity in supramodal regions with widespread cortical projections such as the ventral tegmental area. Intracortical EEG responses in humans show that nociceptive cortical processing is initiated in parallel in sensory, motor and limbic areas; it progresses rapidly to the recruitment of anterior insular and fronto-parietal networks, and finally to the activation of perigenual, posterior cingulate and hippocampal structures. Functional connectivity between sensory and high-level networks increases during the first second post-stimulus, which may be determinant for access to consciousness. A model is described, progressing from unconscious sensori-motor and limbic processing of spinothalamic and spino-parabrachial input, to an immediate sense of awareness supported by coordinated activity in sensorimotor and fronto-parieto-insular networks, and leading to full declarative consciousness through integration with autobiographical memories and self-awareness, involving posterior cingulate and medial temporal areas. This complete sequence is only present during full vigilance states. We contend, however, that even in unconscious subjects, repeated limbic and vegetative activation by painful stimuli via spino-amygdalar pathways can generate implicit memory traces and stimulus-response abnormal sequences, possibly contributing to long-standing anxiety or hyperalgesic syndromes in patients surviving coma.
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TL;DR: These results identify the amygdalar representations of noxious stimuli that are functionally required for the negative affective qualities of acute and chronic pain perception.
Abstract: An ensemble of neurons in the basolateral amygdala (BLA) has been identified that encodes nociceptive information across pain modalities, including pain evoked by noxious thermal and mechanical stimuli. Methods are provided for screening candidate agents for inhibition of neural activity of the BLA nociceptive ensemble. Screening assays further include determining the effectiveness of candidate agents in alleviating pain and reducing aversive pain avoidance behavior.
198 citations
TL;DR: This review aims to discuss recent advances in the understanding of circuit connectivity in the mammalian brain at the level of regional contributions and specific cell types in acute and chronic pain.
Abstract: Chronic, pathological pain remains a global health problem and a challenge to basic and clinical sciences. A major obstacle to preventing, treating, or reverting chronic pain has been that the nature of neural circuits underlying the diverse components of the complex, multidimensional experience of pain is not well understood. Moreover, chronic pain involves diverse maladaptive plasticity processes, which have not been decoded mechanistically in terms of involvement of specific circuits and cause-effect relationships. This review aims to discuss recent advances in our understanding of circuit connectivity in the mammalian brain at the level of regional contributions and specific cell types in acute and chronic pain. A major focus is placed on functional dissection of sub-neocortical brain circuits using optogenetics, chemogenetics, and imaging technological tools in rodent models with a view towards decoding sensory, affective, and motivational-cognitive dimensions of pain. The review summarizes recent breakthroughs and insights on structure-function properties in nociceptive circuits and higher order sub-neocortical modulatory circuits involved in aversion, learning, reward, and mood and their modulation by endogenous GABAergic inhibition, noradrenergic, cholinergic, dopaminergic, serotonergic, and peptidergic pathways. The knowledge of neural circuits and their dynamic regulation via functional and structural plasticity will be beneficial towards designing and improving targeted therapies.
131 citations
Cites background from "Pain and consciousness."
...Conscious pain, on the other hand, has been suggested to involve a higher order network that enables the generation of the percept under the influence of learning, expectation, and current affective state of the individual (18, 99, 101, 196)....
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TL;DR: The goal of this review is to summarize current findings in preclinical research, employing the SNI model as a tool for identifying pathophysiological mechanisms of neuropathic pain and testing pharmacological agent.
Abstract: Neuropathic pain is a pathological condition induced by a lesion or disease affecting the somatosensory system, with symptoms like allodynia and hyperalgesia. It has a multifaceted pathogenesis as it implicates several molecular signaling pathways involving peripheral and central nervous systems. Affective and cognitive dysfunctions have been reported as comorbidities of neuropathic pain states, supporting the notion that pain and mood disorders share some common pathogenetic mechanisms. The understanding of these pathophysiological mechanisms requires the development of animal models mimicking, as far as possible, clinical neuropathic pain symptoms. Among them, the Spared Nerve Injury (SNI) model has been largely characterized in terms of behavioral and functional alterations. This model is associated with changes in neuronal firing activity at spinal and supraspinal levels, and induces late neuropsychiatric disorders (such as anxious-like and depressive-like behaviors, and cognitive impairments) comparable to an advanced phase of neuropathy. The goal of this review is to summarize current findings in preclinical research, employing the SNI model as a tool for identifying pathophysiological mechanisms of neuropathic pain and testing pharmacological agent.
55 citations
TL;DR: Attending to, expressing, and understanding previously unacknowledged psychological distress unrelated to pain may facilitate recovery from chronic pain after early adversity and constitute an unintentional analog of the phenomenon of self-injury in patients with borderline personality disorder.
Abstract: Background Early adversity predisposes to chronic pain, but a mechanistic explanation is lacking. Survivors of early adversity with chronic pain often seem impaired in their ability to be aware of, understand, and express distressing emotions such as anger and fear in social contexts. In this context, it has been proposed that pain may at times serve as a "psychic regulator" by preventing awareness of more intolerable emotions. Method This narrative review builds on the premise that physical pain and emotional pain are conscious experiences that can compete for selective attention. We highlight mechanisms whereby the consequences of early adversity may put emotional pain at a competitive disadvantage. A case history, supportive research findings, and an evidence-based neurobiological model are presented. Results Arising from abuse or neglect in childhood, impairments in the adult capacity to attend to and/or conceptualize the emotional meaning of felt distress may be associated with impaired engagement of the default network and impaired top-down modulation of affective response generation processes. Persistent and poorly conceptualized affective distress may be associated with reduced emotion regulation ability, reduced vagal tone, increased inflammation, and amplified nociceptive signals. Attention to physical pain may be reinforced by the temporary reduction in negative emotions that it causes. Conclusions These processes jointly promote biased competition favoring attention to physical pain and away from one's own emotions. They may constitute an unintentional analog of the phenomenon of self-injury in patients with borderline personality disorder in whom the intentional infliction of physical pain serves to downregulate intense emotional distress. Attending to, expressing, and understanding previously unacknowledged psychological distress unrelated to pain may facilitate recovery from chronic pain after early adversity. Mechanistic studies that can validate this clinically derived neurobiological hypothesis are urgently needed.
40 citations
Cites background from "Pain and consciousness."
...This attentional focus on pain could play a role in central sensitization and may be particularly relevant given the growing body of evidence (reviewed by Garcia-Larrea and Bastuji (128)) for unconscious nociceptive processing and for the role of attentional mechanisms in moderating whether unconscious pain representations become consciously accessible (i.e., supporting the same neurocognitive models of conscious access described previously in relation to emotion (14))....
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...This attentional focus on pain could play a role in central sensitization and may be particularly relevant given the growing body of evidence (reviewed by Garcia-Larrea and Bastuji (128)) for unconscious nociceptive processing and for the role of...
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TL;DR: The results underscore the anterior insula's reverse role, i.e., receiving and integrating very rapidly limbic with sensory input, to initiate a perceptual decision on the stimulus ‘painfulness’.
Abstract: Two parallel di-synaptic routes convey nociceptive input to the telencephalon: the spino-thalamic system projecting principally to the posterior insula, and the spino-parabrachial pathway reaching the amygdalar nucleus Interplay between the two systems underlies the sensory and emotional aspects of pain, and was explored here in humans with simultaneous recordings from the amygdala, posterior and anterior insulae Onsets of thermo-nociceptive responses were virtually identical in the posterior insula and the amygdalar complex, but no significant functional connectivity was detected between them using coherence analysis Anterior insular sectors responded with ~30 ms delay relative to both the posterior insula and the amygdala While intra-insular functional correlation was significant during the whole analysis period, coherence between the anterior insula and the amygdala became significant after 700 ms of processing Phase lags indicated information transfer initially directed from the amygdalar complex to the insula Parallel but independent activation of sensory and limbic nociceptive networks appear to converge in the anterior insula in less than one second While the anterior insula is often considered as providing input into the limbic system, our results underscore its reverse role, ie, receiving and integrating very rapidly limbic with sensory input, to initiate a perceptual decision on the stimulus ‘painfulness’
34 citations
References
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TL;DR: A useful conceptual framework is provided for matching the functional imaging findings with the specific role(s) played by this structure in the higher-order cognitive functions in which it has been implicated, and activation patterns appear to converge with anatomical and connectivity data in providing preliminary evidence for a functional subdivision within the precuneus.
Abstract: Functional neuroimaging studies have started unravelling unexpected functional attributes for the posteromedial portion of the parietal lobe, the precuneus. This cortical area has traditionally received little attention, mainly because of its hidden location and the virtual absence of focal lesion studies. However, recent functional imaging findings in healthy subjects suggest a central role for the precuneus in a wide spectrum of highly integrated tasks, including visuo-spatial imagery, episodic memory retrieval and self-processing operations, namely first-person perspective taking and an experience of agency. Furthermore, precuneus and surrounding posteromedial areas are amongst the brain structures displaying the highest resting metabolic rates (hot spots) and are characterized by transient decreases in the tonic activity during engagement in non-self-referential goal-directed actions (default mode of brain function). Therefore, it has recently been proposed that precuneus is involved in the interwoven network of the neural correlates of self-consciousness, engaged in self-related mental representations during rest. This hypothesis is consistent with the selective hypometabolism in the posteromedial cortex reported in a wide range of altered conscious states, such as sleep, drug-induced anaesthesia and vegetative states. This review summarizes the current knowledge about the macroscopic and microscopic anatomy of precuneus, together with its wide-spread connectivity with both cortical and subcortical structures, as shown by connectional and neurophysiological findings in non-human primates, and links these notions with the multifaceted spectrum of its behavioural correlates. By means of a critical analysis of precuneus activation patterns in response to different mental tasks, this paper provides a useful conceptual framework for matching the functional imaging findings with the specific role(s) played by this structure in the higher-order cognitive functions in which it has been implicated. Specifically, activation patterns appear to converge with anatomical and connectivity data in providing preliminary evidence for a functional subdivision within the precuneus into an anterior region, involved in self-centred mental imagery strategies, and a posterior region, subserving successful episodic memory retrieval.
4,342 citations
TL;DR: A review of available studies examining the human amygdala covers both lesion and electrical stimulation studies as well as the most recent functional neuroimaging studies, and attempts to integrate basic information on normal amygdala function with the current understanding of psychiatric disorders, including pathological anxiety.
Abstract: Here we provide a review of the animal and human literature concerning the role of the amygdala in fear conditioning, considering its potential influence over autonomic and hormonal changes, motor behavior and attentional processes. A stimulus that predicts an aversive outcome will change neural transmission in the amygdala to produce the somatic, autonomic and endocrine signs of fear, as well as increased attention to that stimulus. It is now clear that the amygdala is also involved in learning about positively valenced stimuli as well as spatial and motor learning and this review strives to integrate this additional information. A review of available studies examining the human amygdala covers both lesion and electrical stimulation studies as well as the most recent functional neuroimaging studies. Where appropriate, we attempt to integrate basic information on normal amygdala function with our current understanding of psychiatric disorders, including pathological anxiety.
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TL;DR: It is argued that complex cognitive–emotional behaviours have their basis in dynamic coalitions of networks of brain areas, none of which should be conceptualized as specifically affective or cognitive.
Abstract: The current view of brain organization supports the notion that there is a considerable degree of functional specialization and that many regions can be conceptualized as either 'affective' or 'cognitive'. Popular examples are the amygdala in the domain of emotion and the lateral prefrontal cortex in the case of cognition. This prevalent view is problematic for a number of reasons. Here, I will argue that complex cognitive-emotional behaviours have their basis in dynamic coalitions of networks of brain areas, none of which should be conceptualized as specifically affective or cognitive. Central to cognitive-emotional interactions are brain areas with a high degree of connectivity, called hubs, which are critical for regulating the flow and integration of information between regions.
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"Pain and consciousness." refers background in this paper
...…shown that unconscious processing remains restricted to stimulus-specific sensory cortices –with frontal activation in some cases (Beck et al., 2001; Pessoa, 2008; van Gaal et al., 2010), whereas conscious access involves a distributed network which allies sensory-specific regions to…...
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...…reactions to emotionally salient stimuli can also initiate cognitive activation, via its output to the cortex and subcortical nuclei projecting to widespread cortical areas (locus coeruleus, raphe nuclei, ventral tegmental area) (Pessoa, 2008; Pessoa and Adolphs, 2010; Mitchell and Greening, 2011)....
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TL;DR: A taxonomy is proposed that distinguishes between vigilance and access to conscious report, as well as between subliminal, preconscious and conscious processing, and that conscious perception is systematically associated with surges of parieto-frontal activity causing top-down amplification.
1,693 citations