中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

basic research and clinical data in an attempt to derive a cohesive model which explains the behavioral effects of the drug. Johnson is an experimental psychologist, and his work underlies many of the chapters which suggest that lithium decreases the behavioral response to novel external stimuli. He then utilizes this foundation to propose a cognitive model for lithium's anti-manic action, its inhibition of violent impulsivity, and its prophylactic effects in recurrent depression. Previous formulations which were clinically based, such as that of Mabel Blake Cohen and her associates, stressed the primacy of depression and noted the \"manic defense\" as an attempt to ward off intolerable depression. In direct contrast, Johnson views mania as the primary disturbance in bipolar disorder. He considers depression in bipolar disease as an over-zealous homeostatic inhibitory responsf to a maniaassociated cognitive overload. Consistent with this, he believes, lit lum exerts its anti-manic effect by decreasing cognitive processing in a manner analogous to his animal studies. Johnson also suggests that lithium exerts its prophylactic effect in recurrent depressions by treating subclinical mania. These concepts are supported by the work of Johnson's associate, Kukopulos, to whom the book is dedicated. The bulk of the research which describes the cognitive disturbance in mania is complex, however, and uncomfortably open to multiple interpretations. Recognized as a preliminary effort, Johnson's formulation may help to guide further research. Although Johnson clearly traces lithium actions through a broad range of subjects, his discussion of the neurophysiological aspects of this drug is notably spotty. In particular, Johnson ignores the work of Svensson, DeMontigny, Aghajanian, and others who suggest that serotonergic systems may play an important role in the antidepressant actions of lithium. As a result, he fails to discuss one of the most important current uses of lithium: as an agent used in conjunction with antidepressant medications to increase treatment response in medication-resistant forms of depression. Lithium augmentation of antidepressant medication also challenges the formulation presented by Johnson. This formulation suggests that lithium should have no therapeutic value in patients, such as those with endogenous depression, who already \"under-process\" cognitive information. The omission of lithium augmentation in depression is clearly unfortunate in this text. Overall, this volume demonstrates the benefits of a single-authored text. It it clearly organized and readable. The bibliography is also broad and useful. In this book, Johnson primarily addresses a research audience, and his model seems designed to stimulate thought rather than to improve clinical technique. In this capacity, his book will be of most interest to behavioral psychologists. Other books, focusing purely on clinical data, may be more useful to clinicians. Nevertheless, the clear organization, the large bibliography, and the thoughtful presentation may make this text a useful addition to a clinical library as well.

The Body in Pain: The Making and Unmaking of the World.

https://www.wisebrain.org/media/Papers/BerridgeRobinson%26AldridgeDissectingcomponentsofrewardCurrentOpinPharm2009.pdf

Dissecting components of reward: 'liking', 'wanting', and learning.

Chronic pain is one of the most prevalent health problems in our modern world, with millions of people debilitated by conditions such as back pain, headache and arthritis. To address this growing problem, many people are turning to mind-body therapies, including meditation, yoga and cognitive behavioural therapy. This article will review the neural mechanisms underlying the modulation of pain by cognitive and emotional states - important components of mind-body therapies. It will also examine the accumulating evidence that chronic pain itself alters brain circuitry, including that involved in endogenous pain control, suggesting that controlling pain becomes increasingly difficult as pain becomes chronic.

/pdf/cognitive-and-emotional-control-of-pain-and-its-disruption-2zouzyfeyw.pdf

Cognitive and emotional control of pain and its disruption in chronic pain

/pdf/beck-depression-inventory-iinituitenoyi-kao-cha-3143h0pleh.pdf

Beck Depression Inventory-IIについての一考察

Pain and pleasure are powerful motivators of behaviour and have historically been considered opposites. Emerging evidence from the pain and reward research fields points to extensive similarities in the anatomical substrates of painful and pleasant sensations. Recent molecular-imaging and animal studies have demonstrated the important role of the opioid and dopamine systems in modulating both pain and pleasure. Understanding the mutually inhibitory effects that pain and reward processing have on each other, and the neural mechanisms that underpin such modulation, is important for alleviating unnecessary suffering and improving well-being.

A common neurobiology for pain and pleasure.

Induction of depressed mood disrupts emotion regulation neurocircuitry and enhances pain unpleasantness

Relief fits the definition of a reward. Unlike other reward types the pleasantness of relief depends on the violation of a negative expectation, yet this has not been investigated using neuroimaging approaches. We hypothesized that the degree of negative expectation depends on state (dread) and trait (pessimism) sensitivity. Of the brain regions that are involved in mediating pleasure, the nucleus accumbens also signals unexpected reward and positive prediction error. We hypothesized that accumbens activity reflects the level of negative expectation and subsequent pleasant relief. Using fMRI and two purpose-made tasks, we compared hedonic and BOLD responses to relief with responses during an appetitive reward task in 18 healthy volunteers. We expected some similarities in task responses, reflecting common neural substrates implicated across reward types. However, we also hypothesized that relief responses would differ from appetitive rewards in the nucleus accumbens, since only relief pleasantness depends on negative expectations. The results confirmed these hypotheses. Relief and appetitive reward task activity converged in the ventromedial prefrontal cortex, which also correlated with appetitive reward pleasantness ratings. In contrast, dread and pessimism scores correlated with relief but not with appetitive reward hedonics. Moreover, only relief pleasantness covaried with accumbens activation. Importantly, the accumbens signal appeared to specifically reflect individual differences in anticipation of the adverse event (dread, pessimism) but was uncorrelated to appetitive reward hedonics. In conclusion, relief differs from appetitive rewards due to its reliance on negative expectations, the violation of which is reflected in relief-related accumbens activation.

/pdf/relief-as-a-reward-hedonic-and-neural-responses-to-safety-1h593y5dm8.pdf

Relief as a Reward: Hedonic and Neural Responses to Safety from Pain

Context can influence the experience of any event. For instance, the thought that “it could be worse” can improve feelings towards a present misfortune. In this study we measured hedonic feelings, skin conductance, and brain activation patterns in 16 healthy volunteers who experienced moderate pain in two different contexts. In the “relative relief context,” moderate pain represented the best outcome, since the alternative outcome was intense pain. However, in the control context, moderate pain represented the worst outcome and elicited negative hedonic feelings. The context manipulation resulted in a “hedonic flip,” such that moderate pain elicited positive hedonics in the relative relief context. Somewhat surprisingly, moderate pain was even rated as pleasant in this context, despite being reported as painful in the control context. This “hedonic flip” was corroborated by physiological and functional neuroimaging data. When moderate pain was perceived as pleasant, skin conductance and activity in insula and dorsal anterior cingulate were significantly attenuated relative to the control moderate stimulus. “Pleasant pain” also increased activity in reward and valuation circuitry, including the medial orbitofrontal and ventromedial prefrontal cortices. Furthermore, the change in outcome hedonics correlated with activity in the periacqueductal grey (PAG) of the descending pain modulatory system (DPMS). The context manipulation also significantly increased functional connectivity between reward circuitry and the PAG, consistent with a functional change of the DPMS due to the altered motivational state. The findings of this study point to a role for brainstem and reward circuitry in a context-induced “hedonic flip” of pain.

/pdf/the-importance-of-context-when-relative-relief-renders-pain-474frgj1jl.pdf

The importance of context: When relative relief renders pain pleasant

Intense itch and urge to scratch are the major symptoms of many chronic skin ailments, which are increasingly common. Vicious itch-scratch cycles are readily established and may diminish quality of life for those afflicted. We investigated peripheral and central processing of two types of itch sensation elicited by skin-prick tests of histamine and allergen solutions. Itch-related skin blood flow changes were measured by laser Doppler in 14 subjects responsive to type I allergens and 14 nonatopic subjects. In addition, this study examined central processing of both types of itch using functional magnetic resonance imaging (fMRI). Itch perception and blood flow changes were significantly greater when itch was induced by allergens compared with histamine. Both types of itch correlated significantly with activity in the genual anterior cingulate, striatum, and thalamus. Moreover, itch elicited by allergens activated orbitofrontal, supplementary motor, and posterior parietal areas. Histamine-induced itch also significantly correlated with activation in the insula bilaterally. The identification of limbic and ventral prefrontal activation in two types of itch processing likely reflects the subjects' desire to relieve the itch sensation by scratching, and these regions have been repeatedly associated with motivation processing. A dysfunction of the striato-thalamo-orbitofrontal circuit is believed to underlie the failure to regulate motivational drive in disorders associated with strong urges, e.g., addiction and obsessive compulsive disorder. The patterns of itch-induced activation reported here may help explain why chronic itch sufferers frequently self-harm through uncontrollable itch-scratch cycles.

Siri Leknes

Papers

A common neurobiology for pain and pleasure.

Induction of depressed mood disrupts emotion regulation neurocircuitry and enhances pain unpleasantness

Relief as a Reward: Hedonic and Neural Responses to Safety from Pain

The importance of context: When relative relief renders pain pleasant

Itch and Motivation to Scratch: An Investigation of the Central and Peripheral Correlates of Allergen- and Histamine-Induced Itch in Humans