Neurocognitive aspects of pain perception - 정리중... 멋진 자료

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Pain is a highly subjective sensation with a complex and often non-linear relationship between nociceptive input and pain perception.

- 통증은 복잡한 주관적인 감각으로 유해자극성 input과 통증지각사이에 직선적인 관계를 갖지 않음. 

brain 영역에서 통증 인지단계의 pain modulation mechanism

통증은 affective dimension(감정적 차원, 정서적 차원)에서의 진단과 치료법이 반드시 필요.

이 영역은 진단도 직관적이고, 치료도 직관적인 영역. 

이 영역의 통증은 환자 자신의 감정과 믿음에 의지해서 스스로 통증기억을 대뇌에 저장하는 것이다. pain attenion에 의해서 

만성 통증은 환자와 깊은 신뢰(rapport)를 형성한뒤, pain distraction method(EFT)를 이용하면 즉석에서 통증을 줄여줄 수 있다. 

인체를 전체 통합의 관계에서 파악해야 하기때문에 통증을 Trigger한 요소는 반드시 찾아서 치료해주어야 하는 과제는 그대로 남아있음을 기억해야 한다. 

panic bird...

통증의 affective dimension(감정적 차원) 이해

1. 감정적 차원의 통증 두가지

1) 고민(feeling of unpleasantness, short-term, distress) 통증

2) 고통(secondary affect, long-term, suffering) 통증으로 구분

2. pain affective는 세가지 감각경로

1) Nociceptive sensory processes

2) extroceptive(sight, sound) sensory processes

3) interoceptive(startle, autonomic response) sensory processes가 공평하게 관여함. 

나라가 정리한 참고논문)

Psychological and Neural Mechanisms of the affective dimens.pdf

The perception of pain is sensitive to various mental processes such as the feelings and beliefs that someone has about pain. It is therefore not exclusively driven by the noxious input. Attentional modulation involving the descending pain modulatory system has been examined extensively in neuroimaging studies. However, the investigation of neural mechanisms underlying more complex cognitive modulation is an emerging field in pain research. 

- 통증 인지는 환자의 통증에 대한 감정(feeling)과 믿음(belief)에 민감

- 그래서 통증은 전적으로 유해자극성 input에 의존하지는 않음. 

- 하행성 통증 조절에 의한 주의적 변조는 뇌지도 연구에서 많이 탐구됨. 하지만 복잡한 인지적 통증변조에 의한 신경 기전의 탐구는 새로 떠오르는 탐구분야임. 

Recent findings indicate an engagement of the ventrolateral prefrontal cortex during more complex modulation, leading to a change or re-appraisal of the emotional significance of pain. Taking placebo-induced analgesia as an example, we discuss the contribution of attention, expectation and re-appraisal as three basic mechanisms that are important for the cognitive modulation of pain.

- cognitive modulation of pain의 중요한 세가지는 주의(attention), 기대(expectation), 재평가(reappraisal임. 이는 통증의 인지조절을 위해 중요한 영역임. 

The impact of cognitive processes on the perception of pain

Pain is a highly subjective sensation with a complex and often non-linear relationship between nociceptive input and pain perception. A variety of cognitive processes have been shown to influence pain perception and bias nociceptive processing in the human brain. One clear example is how the pain experience depends upon the focus of attention: it is perceived as less intense when somebody is distracted from pain[1], yet increases when attention is focused on pain [2]. 

- 통증은 복잡한 주관적인 감각으로 유해자극성 input과 통증지각사이에 직선적인 관계를 갖지 않음. 다양한 인지 과정은 통증지각에 영향을 주고 ......

- 통증이 대한 과도한 주의가 만성통증에 중요한 역할을 함. 

Attentional Modulation of Spatial Integration of Pain.pdf

Among the cognitive variables influencing pain, the brain mechanisms underlying attentional control have probably been the most extensively studied [3–9].

Distraction Modulates Anterior Cingulate Gyrus Activations during the cold pressor test.pdf

Imaging attentional modulation of pain in the PAG in human.pdf

Imaging how attention modulates pain in human using functional MRI.pdf

Modulation of pain processing in hyperalgesia by cognitive demand.pdf

A re-examination of pain–cognition interactions for neuroimaging. PAIN.pdf

Attention to painful stimulation enhances gamma-band activity and synchronization in human sensorimotor cortex.pdf

However, attentional processes do not stand alone. They interact with mechanisms supporting the formation of expectations about pain and reappraisal of the experience or meaning of pain, these, in turn, are influenced by prior experience. 

- 하지만 통증에 대한 과도한 주의 홀로 만성통증에 관여하지 않음. pain attention, expectation about pain, reappraisal of the experience(meaning of pain)이 상호 작용하여 만성통증이 됨. 

For instance, patients whose pain is resistant to medication might feel helpless and, as a consequence, allocate more attention to pain than other patients. Moreover, previous experiences enable us to interpret signs that signal the appearance or disappearance of pain. Patients who respond well to analgesic treatment might, for instance, already disengage from pain when they know that medication is available. 

- 예를들어, 진통제에 듣지 않는 통증환자는 희망이 없게 느껴지고, 그 결과 다른 환자보도 통증에 대한 과도한 주의가 더욱 심해짐. 게다가 과거의 통증에 대한 경험은 ....

Here, the medication acts as a cue for pain relief. This knowledge is used in placebo analgesia, whereby pain relief is induced by the assumption that one has received a potent painkiller [10]. Similarly, however, the pain might allocate more attention if the medication was accidentally left at home. Based on the knowledge derived from previous pain experiences and stimuli associated with it, a schematic model of pain develops that enables us to make predictions about future pain events. Neural mechanisms underlying learning and expectations about pain and their resultant effect on pain perception have been investigated in numerous studies[11–13].

- 진통제는 통증완화를 위한 신호로 작용함.

--- 통증에 대한 기대와 익힘 신경기전과 통증지각에 대한 연속된 결과는 많이 연구됨.  

Psychological pain research, however, emphasizes that the schematic model of pain is further influenced by more

complex cognitions, particularly by those related to the perceived threat of pain [14–16]. This type of cognition focuses on the subjective meaning that pain has for the individual. For example, pain might be perceived as more threatening if one believes that it signals a life-threatening pathological process that will have a long-lasting impact on their life. Like attentional and expectational processes, such cognitions can amplify and also attenuate pain. A heightened perceived threat value of pain is associated with a negative psychological adjustment as reflected, for instance, by catastrophic thinking and increased anxiety levels [16], consequently producing higher pain-intensity ratings [17]. Importantly, higher threat values have also been linked to maladaptive coping and higher pain intensity levels in chronic pain sufferers [14]. 

- 심리학적 통증조사는 통증의 설계모델을 강조함. 

- 통증은 사람이 오랫동안 생명을 위협하는 병리적과정 신호로 믿어진다면 좀더 위협적으로 지각됨. 

- 통증에 대한 주의와 호전되지 않을 것이라는 비정상적인 기대는 통증을 악화시킴. 

- 통증에 대한 파멸적인 생각(catastrophic thinking)은 두려움을 증대하고 통증강도 비율을 더욱 악화시킴. 

Conversely, a reappraisal of pain that makes pain less threatening leads to a decrease in pain ratings (e.g. Ref. [18]), an aspect that has only recently become a focus of neuroimaging studies on pain (see Box 1 for differentiation of attentional control and cognitive change).

- 역으로 통증의 재의미는 통증비율을 감소시키는 역할을 함. 

In this review, we summarize recent findings on 

(i) the neural mechanisms underlying the attentional control of pain, 

(ii) the influence of expectations, and 

(iii) reappraisal and discuss the involvement of these processes in placebo-induced analgesia as a clinical example of cognitive pain modulation. 

Although this article focuses on cognitive aspects of pain modulation, it should be noted that processes described here are closely related to emotional factors [19] and their impact on pain experience, which are reviewed elsewhere [20].

- 이 논문이 통증조절의 인지적 측면에 초점을 맞추지만, 그것은 감정적 요소와 연관된..... 

Neural mechanisms of cognitive pain modulation

Attention

Attention modulates perception and cognition by allocating processing resources to relevant external and internal events. It thereby amplifies behavioral and physiological responses to relevant events and attenuates responses to irrelevant events [21]. The highly subjective and behaviorally relevant experience of pain is particularly susceptible to these attentional modulations. 

- 통증에 대한 주의는 통증지각과 인지를 변조함. 

Psychophysical studies indicate that attention can modulate sensory and affective aspects of pain, possibly mediated by a modulation of the spatial integration of pain [2,22,23]. Research during the past decades has started to unravel the underlying neural substrates. Functional imaging studies showed that distraction from pain reduces pain-related activations in most brain areas that are related to sensory, cognitive and affective aspects of pain, including the primary and secondary somatosensory cortices (SI and SII), thalamus, insula and anterior cingulate cortex (ACC) [3–5,7,24,25]. 

The results of electrophysiological studies provided additional information that attention affects later responses more than earlier ones [26]. Furthermore, attention yields an increase in functional coupling between key brain regions involved in pain processing [9,27], implying that attentional modulation does not only result in altered local activation but also affects the functional integration of activation. These attentional modulations correlate nicely with the perceptual effects and correspond well to attentional modulations of sensory processing in other modalities [28].

A pivotal question for understanding attentional modulations of pain is where and how these effects are exerted. 

Numerous studies in other modalities compared different levels of attentional control and identified circuitries of

higher-order frontal and parietal areas, which are presumed to mediate top-down attentional influences on sensory

processing (for reviews, see Refs [21,28–30]). There is no reason to doubt that these brain areas are also involved

in the attentional control of pain. However, direct evidence for this is lacking, presumably because of the inherent difficulty in grading attention to pain (Figure 1). 

Pain attracts attention per se and can rarely be ignored. Researchers have tried to circumvent this problem by

applying paradigms in which subjects actively engage in distracting tasks and compared these distraction conditions

to conditions in which subjects attended to pain. This contrast compares different foci of attention and unravels the expected attentional effects on pain processing. 

Figure 1. Investigating attentional modulation of pain. To investigate the effect of attention on pain, ideally, the perception and neural processing of a noxious stimulation when subjects focus all their attention on the stimulation (A pain) would be compared with a condition whereby no attention is paid to the noxious input (A neutral). The difference between the conditions provides an estimate for the influence that the amplitude or amount of attention has on pain (D attention  amplitude). In most studies on attentional modulation of pain, subjects are instructed to either perform a discrimination task on the noxious stimulation or count the painful stimuli to keep the focus of attention on pain, whereas, typically no specific instruction is given in the control task. However, because pain automatically attracts attention (particularly in the absence of other sensory input), the validity of the ‘no attention to pain’ control condition is limited. Alternatively, attention to pain (A pain) has been compared with a condition that is equally demanding of attention, but not focused on pain (A other than pain). As an example, subjects were instructed to count deviant painful stimuli in the ‘A pain’ (i.e. a shortlasting increase in temperature) and deviant acoustic stimuli in the ‘A other than pain’ condition [24]. Although this comparison (D attention focus) provides information about attentional processes specific for pain, it does not identify brain areas with activation level that co-vary with the amount of attention to pain. Note that the broken line pepresents a hypothetical inverted U-shaped relationship between amplitude and focus of attention.

However, the level of attention might be similar for attention and distraction conditions (Figure 1), so the comparison of conditions does not enable identification of brain areas that specifically influence pain processing via attentional mechanisms. Moreover, even distraction paradigms cannot ensure that attention is effectively diverted from pain.

So far, attentional modulations of pain are supposed to share the general mechanisms and substrates of attentional

modulations of sensory processing. However, the exceptionally close interaction between attention and pain seems to involve pain-specific features that are not necessarily known from other modalities. Interaction analyses taken during distraction from pain revealed brain areas that were more strongly activated than expected from the simple summation of distraction tasks and pain [4–6].

These areas particularly included the prefrontal cortex, ACC and the brainstem periaqueductal gray (PAG). Interestingly, these structures have been associated with descending pain modulation as characterized in animals [31]

(Box 2). This network subserves opioid-mediated analgesia and mainly acts on the level of the spinal cord dorsal-horn.

The results of the functional imaging studies indicate that distraction might at least partly act via activation of this descending pain modulatory system (see Ref. [32] for an overview). 

The Cerebral Signature for Pain Perception and its modulation.pdf

This is further corroborated by a study showing that distraction increases functional connectivity within this network [6] and the underlying descending cortical–brainstem pathways in humans are confirmed in vivo by diffusion tensor imaging [33]. Taken together, attention might modulate pain perception at least partially via a pain-specific opiate-sensitive descending modulatory pathway that regulates nociceptive processing largely at the level of the spinal cord dorsal-horn. This pain modulatory system might complement, interact and overlap with a more general system of attentional control, which has been well characterized in other modalities. Functionally, both networks might enable behavioral flexibility, which is limited by the involuntary attentional demands of pain.

Expectation

Expectations about upcoming events enable an organism to adjust sensory, cognitive and motor systems for adequate

neural and behavioral responses. When a noxious stimulation is signaled by a cue, the expectation period between cue and stimulus is characterized by a signal increase either within or adjacent to brain areas that are subsequently activated by pain itself, that is, regions such as SI, ACC, insula, thalamus, PAG, cerebellum and putamen [34–37]. 

Crucially, the expectation of high pain intensity [37–39] and, consequently, increased anticipatory activation in contralateral SI, bilateral ACC, anterior insula and medial prefrontal cortex [35] were related to higher intensity ratings of subsequent pain. During any perceptual process, expectations are compared to the bottom-up sensory information. 

The subjective experience of pain. Where expectations become reality.pdf

Isolating the Modulatory Effect of Expectation on pain transmission.pdf

These expectations are either confirmed or violated by the noxious input (Figure 2). Two recent functional magnetic resonance imaging (fMRI) studies examined the relative strength of expectations that bias perception when these expectations are violated [38,39]. To identify brain areas sensitive to the expectation of a decreased intensity, incorrectly signaled high-level pain stimuli were compared with correctly cued stimuli of the same stimulation intensity. Pain-intensity ratings showed that the same stimuli were rated as less intense when subjects were expecting a lower intensity. At the neural level, this expectation of a low- but application of a high-level stimulus was reflected by less activation in many brain areas related to pain processing compared with the matched ‘high cue, high pain-intensity’ condition.

This finding indicates that the neural processing during stimulus application is crucially determined by prior knowledge of the stimulus. Interestingly, a bias towards increased pain (i.e. expectation of a high pain stimulus that is followed by low-level stimulation; Figure 2d) was neither observed in the pain-intensity rating nor at the neuronal level.

If expectations enable an organism to prepare for the upcoming sensory input, it is vital to detect discrepancies between expected and perceived features so that expectations can be updated if necessary. Ploghaus et al. [11] were the first to identify brain activation consistent with this violation of expectations. By using a model-based imaging approach they showed activation in the hippocampal system, superior frontal gyrus, posterior parietal cortex and cerebellum. The aim of this approach was to provide insights into ‘how’ the brain learns about pain over time by considering the history of successful (i.e. confirmed) and unsuccessful (i.e. violated) learning trials [40]. Subsequent studies used more complex algorithms to model learning about pain with a higher temporal resolution, enabling identification of brain regions involved in higher-order learning and the prediction of pain relief [12,13]. This promising computational approach will not only aid the elucidation of neural mechanisms underlying the influence of expectations on pain but also shed light on individual differences and biases in pain-related learning.

Figure 3. Possible neural pathways of cognitive pain modulation. Cognitive modulations of pain are related to activation of prefrontal brain areas (DLPFC, VLPFC and ACC; shown in orange), which modulate activation in pain-associated

regions in the cortex (ACC, SI, SII/insula and thalamus), brainstem and dorsal horn (e.g. the PAG and dorsal horn; shown in blue). Attention has been shown to mainly engage the DLPFC and ACC, whereas reappraisal relates particularly to the VLPFC. Expectation has been associated with both densely interconnected prefrontal areas. The DLPFC is connected to the ACC, which, in turn, projects to thalamus and the PAG, a core component of the descending pain modulatory system. This system eventually facilitates and/or inhibits pain processing at the level of the spinal cord dorsal horn. Direct cortico–cortical modulations from VLPFC and DLPFC to pain-associated cortical areas are probable but have not been directly

shown yet (broken lines). Areas most closely associated with pain (SI, ACC, SII/ insula and thalamus) are densely interconnected, as indicated by the green circle. For the sake of clarity, ascending projections are not fully shown. Abbreviations: ACC, anterior cingulate cortex; DLPFC, dorsolateral prefrontal cortex; PAG, periaqueductual gray; SI, primary somatosensory cortex; SII, secondary somatosensory cortex; VLPFC, ventrolateral prefrontal cortex.

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와우~~ 멋진 자료네요..!!! 감사합니다^^

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pain distraction method ...
공감!! 강력하게 동의 동의합니다. 만3년 반 동안 그 무시무시한 통증이 " 마음이 보내는 경고 " 였음을 " 마음의 통증 = 신체의 통증 ... 이 두 통증의 정도가 서로 비례 한다는 사실이 그저 놀랍기만 합니다. distraction.. distraction...

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경험하셨군요..

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감사합니다