Brain mechanisms for pain and pleasure-

Metrics details. As all chefs know, great food can have a transformational impact. A great deal of recent research has gone into using the new techniques from molecular gastronomy and gastrophysics to create innovative meals with delicious original textures and flavours. These novel creations have elicited much excitement from food critiques and diners alike. Much stands to be gained if these developments were to be matched by a better understanding of how the pleasure of food comes about in the brain.

Brain mechanisms for pain and pleasure

Brain mechanisms for pain and pleasure

Brain mechanisms for pain and pleasure

Brain mechanisms for pain and pleasure

Brain mechanisms for pain and pleasure

The control of eating over time involves many different levels of processing as illustrated by the food. Annu Rev Psychol. Even a sensory pleasure such as a sweet taste requires the co-recruitment of additional specialized pleasure-generating neural circuitry to add the positive hedonic impact to the sweetness that elicits liking reactions described in details below [ 458 ]. Behav Brain Res. What is pleasure or core liking? The primate amygdala represents the positive and negative value of visual stimuli during learning. Smell images and the flavour Brain mechanisms for pain and pleasure Steve and kristina kay twins the human brain. In further experiments, they used optogenetics to turn off the signaling pathway in the dorsal raphe nucleus. Brain mechanisms for pain and pleasure, liking can sometimes occur unconsciously, and at other times even conscious pleasure ratings sometimes detach substantially from core affective reactions as people concoct explanations to themselves for how they think they should feel [ 16 — 19 ].

Busty fat mature. Introduction

Each hotspot seems able to recruit the other to unanimously generate amplification of liking. Pain is usually such a negative experience that we rarely think about it in terms of just another sensory modality let alone consider the potential of positive aspects to it. Whether or not pain and pleasure are indeed on a continuum, it still remains scientifically supported that parts of the neural pathways for the two perceptions overlap. Those dual aspects reflect Brain mechanisms for pain and pleasure affective reactions are generated by neural mechanisms, selected in evolution based on their real objective consequences for genetic fitness. The brain is so insensitive to painful stimuli that neurosurgeons do not apply anaesthesia to the brain tissue they operate upon, allowing patients to be awake and completely responsive for the Brain mechanisms for pain and pleasure procedure. This has been shown to include a number Florida freshwater shrimp starting business important regions such as pleasure hotspot regions in subcortical areas of the brain such as the nucleus accumbens and ventral pallidum [ 2829 ]. Scientific American. Nucleus accumbens shell, but not core, tracks motivational value of salt. Brain Res. Leyton M.

Affective neuroscience aims to understand how affect pleasure or displeasure is created by brains.

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Now, a new study from the University of Michigan adds a new twist to dopamine's fun-loving reputation: pain. Using sophisticated brain-scanning and a carefully controlled way of inducing muscle pain, the researchers show that the brain's dopamine system is highly active while someone experiences pain - and that this response varies between individuals in a way that relates directly to how the pain makes them feel. It's the first time that dopamine has been linked to pain response in humans.

It may also yield clues to why some, but not other chronic pain patients may be prone to developing addictions to certain pain medications. And, it gives further evidence that vulnerability to drug addiction is a very individual phenomenon - and one that can't be predicted by current knowledge of genetics and physiology.

The study, which involved 25 healthy men and women, showed that dopamine was active in areas of the brain region known as the basal ganglia, the same region where it has been observed to respond to positive stimuli, such as food or sex. But when the researchers induced pain in the volunteers' jaw muscle, and asked them to rate different aspects of how they were feeling, differences emerged in specific sub-areas of the basal ganglia. That effect persisted even after the researchers controlled for the negative emotional effects caused by the actual research setup, which included a needle inserted into a large jaw muscle, and the expectation of pain and repeated questioning.

Similarly, dopamine release in two other areas of the basal ganglia - the putamen and caudate nucleus - was strongly correlated with the rating of how intense and unpleasant the pain itself was on a scale of 0 to The authors concluded that in some areas of the basal ganglia, dopamine was involved in the assessment of pain itself, while in the ventral area, or nucleus accumbens, it was related to the emotional experience of pain.

To do this, they used the drug raclopride, to which had been attached a short-lived radioactive form of carbon. The researchers also scanned each volunteer's brain using magnetic resonance imaging MRI in order to create a precise map of the brain's structure, and combined that with their PET scans to find the exact areas of dopamine activity.

The volunteers answered questions from two standardized questionnaires repeatedly both in a control no pain state and when their jaw muscles were being injected with harmless salt water in order to cause pain. The questionnaires measure pain and emotion in a standardized way, so that ratings can be compared over time.

None of the participants had a history of medical or psychiatric illness, nor of drug addiction or dependence. The 7 female volunteers were not taking birth control pills and were scanned at the same point in their menstrual cycles. In addition to the differences in dopamine receptor activation in certain areas of the brain across all the participants, the scans also revealed differences between individuals in the level of their dopamine response and their self-rated pain and emotional response.

This kind of variation may help explain the major variation between individuals who are exposed to addictive drugs - some become addicted to the pleasures of the "high" the drugs cause, while others do not. Scott, Ph. The new findings build on previous pain research by Zubieta and his team, which has shown individual variation in the rating of pain, and has visualized the brain's own painkiller system responding to pain and even to the giving of a "placebo" painkiller medication.

Now, the team is working to examine the hormonal and genetic factors that may be different between people whose dopamine systems responded differently to pain.

They also have recently received funding from the National institute of Drug Abuse to study individual variation in the effects and use of opioid painkiller drugs among people with chronic pain. The study was funded by the National Institutes of Health. The U-M team that performed this study is currently seeking participants for additional studies; visit www. No place like home: Species are on the move, but many have nowhere to go University of York Gimme six!

Love songs, bird brains and diffusion tensor imaging. Conversely, in a caudal NAc shell key, microinjections inducing opioid or dopamine stimulation generate wanting, whereas glutamate AMPA blockade instead generates fear, and GABA signals add disgust to the fear [ 75 — 80 ]. Damasio AR. The novella opens many interesting question with regard to well-being and the good life and in particular shows that to allow oneself to be open to the possibility of pleasure of food is also allowing for the deep experiences of the multitude of pleasures. Philos T R Soc B.

Brain mechanisms for pain and pleasure

Brain mechanisms for pain and pleasure

Brain mechanisms for pain and pleasure

Brain mechanisms for pain and pleasure

Brain mechanisms for pain and pleasure

Brain mechanisms for pain and pleasure. Pleasure Center of the Brain: Light It Up

The novella opens many interesting question with regard to well-being and the good life and in particular shows that to allow oneself to be open to the possibility of pleasure of food is also allowing for the deep experiences of the multitude of pleasures.

This is in sharp contrast to the denial of the pleasure of food leading to anhedonia, the lack of pleasure, which is a key constituent component of affective disorders. The science of pleasure has made great strides in recent years [ 4 ], due not in small parts to using food as a pleasure-eliciting stimulus.

As demonstrated in this review, the research has uncovered many of the fundamental brain mechanisms governing eating and pleasure in general. In particular, the brain must make important decisions of how best to balance exploration and exploitation to ensure survival. The model demonstrates the cyclical changes in hunger levels related to the initiation and termination of meals, as they relate to signals from the brain, gut-brain, oral cavity, stomach and intestines, liver and metabolites and body mass.

Model of information flow in the orbitofrontal cortex OFC. The spatial heterogeneity of the human OFC has been revealed with neuroimaging.

Sensory information comes to the OFC where it is available for pattern association between primary e. The OFC participates in multiple modulatory brain-loops with other important structures in the pleasure system such as the nucleus accumbens, ventral pallidum, amygdala and hypothalamus, as well as modulation with autonomic input from the gut.

B Examples of monitoring reward value in medial OFC green was found in a study of orthonasal smell where the activity correlated with subjective ratings of pleasant and unpleasant smell [ 66 ]. Activity in mid-OFC orange correlates with the subjective pleasure of food in a study of selective-satiety [ 33 ]. In contrast, the activity in lateral OFC shown in red was found when changing behaviour in a rapid context-dependent reversal task of simple social interactions [ 84 ]. C A large meta-analysis of neuroimaging studies confirmed the differential functional roles of these regions [ 34 ].

It has also shown the unity of pleasure processing of different rewards, with food, sex, social and higher-order stimuli such as music and money in a unified pleasure system [ 12 , 13 , 74 - 76 , 84 ]. Much remains to be done, but finally science has gained a toehold in understanding how pleasure can come to transform lives.

Understanding the pleasure of food has played a major part in hedonia research and may even offer some insights into well-being. Gastronomy offers the potential to expand on these findings and create exciting experiences and great pleasure. The rise of molecular gastronomy and gastrophysics have afforded chefs with unprecedented control over the production of novel flavours and textures of food [ 78 , 79 ]. These experiences are by their very nature multisensory and like all experiences highly dependent on expectation and prior experiences [ 80 ].

Using scientific tools and insights allows playful chefs to create unique and highly pleasurable dining experiences, e. Both the science and art of cooking stand to benefit much from future collaborations between scientists and chefs, especially in so far this research can help increase the pleasure of eating and well-being.

While it is true that creating great art takes skills and years of practice, it is also important to remember that every moment and every bite of food carries within it the possibility of pleasure.

The brain is built for pleasure and it is through learning to appreciate the extraordinary in ordinary experiences, through pursuing the variety of pleasures rather than the relentless single-minded pursuit hedonism or denial of pleasure asceticism that a life well-lived can be constructed. Dinesen I. In: Anecdotes of destiny. London: Penguin; Kringelbach G. Copenhagen: Erichsen; Kringelbach ML.

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New York: C. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev. Affective neuroscience of pleasure: Reward in humans and animals. Psychopharmacology ; Liking vs.

Neurosci Biobehav Rev. Satiation, satiety and the action of fibre on food intake. Int J Obes. Palatability affects satiation but not satiety. Food reward in the absence of taste receptor signaling. The gustatory cortex and multisensory integration. Shepherd GM. Smell images and the flavour system in the human brain. The olfactory system. In The human nervous system 3rd Ed.

Hedonic hot spot in nucleus accumbens shell: where do mu-opioids cause increased hedonic impact of sweetness? J Neurosci. Opioid limbic circuit for reward: interaction between hedonic hotspots of nucleus accumbens and ventral pallidum.

Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion.

Nat Neurosci. The hedonic brain: A functional neuroanatomy of human pleasure. In pleasures of the brain. Oxford, U. Activation of the human orbitofrontal cortex to a liquid food stimulus is correlated with its subjective pleasantness.

Cerebral Cortex. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Progress in Neurobiology. Berridge KC. Food reward: brain substrates of wanting and liking. Neuroscience and Biobehavioral Reviews. Neuroethology of pleasure. New York: Oxford University Press; 85— Meeting of minds: the medial frontal cortex and social cognition. Nat Rev Neurosci. Exploring the network dynamics underlying brain activity during rest. Prog Neurobiol. Deco G, Kringelbach ML.

Neuron ; Cortical systems involved in appetite and food consumption. In Appetite and body weight: integrative systems and the development of anti-obesity drugs. London: Elsevier; 5— Situational effects on meal intake: a comparison of eating alone and eating with others.

Physiology and Behavior. Slow food, fast food and the control of food intake. Nat Rev Endocrinol. Central and peripheral regulation of food intake and physical activity: pathways and genes. Obesity Silver Spring. An expanded view of energy homeostasis: neural integration of metabolic, cognitive, and emotional drives to eat. Appetite control and energy balance regulation in the modern world: reward-driven brain overrides repletion signals. Int J Obes Lond. Grill HJ, Norgren R.

The taste reactivity test. Mimetic responses to gustatory stimuli in chronic thalamic and chronic decerebrate rats. Brain Res. Rozin P.

Food preference. Amsterdam: Elsevier; The pleasure of taste flavor and food. In Pleasures of the brain. Functional anatomy of taste perception in the human brain studied with positron emission tomography. Human cortical gustatory areas: a review of functional neuroimaging data. Representation of pleasant and aversive taste in the human brain.

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Orbitofrontal involvement in the processing of unpleasant auditory information. European Journal of Neuroscience. Functional localization and lateralization of human olfactory cortex. Representations of pleasant and painful touch in the human orbitofrontal and cingulate cortices.

Beautiful faces have variable reward value: fMRI and behavioral evidence. Fear conditioning in humans: the influence of awareness and autonomic arousal on functional neuroanatomy. Neural contributions to the motivational control of appetite in humans. Eur J Neurosci , vol. Dissociable contributions of the human amygdala and orbitofrontal cortex to incentive motivation and goal selection.

Rolls ET. The brain and emotion. Oxford: Oxford University Press; Taste-olfactory convergence, and the representation of the pleasantness of flavour, in the human brain. Dissociation of neural representation of intensity and affective valuation in human gustation. Human cortical responses to water in the mouth, and the effects of thirst. Journal of Neurophysiology. Different representations of pleasant and unpleasant odors in the human brain.

Dissociated neural representations of intensity and valence in human olfaction. Nature Neuroscience. Functional heterogeneity in human olfactory cortex: an event-related functional magnetic resonance imaging study. Journal of Neuroscience. Abstract reward and punishment representations in the human orbitofrontal cortex. How might our relationships be? How arousing? The effect is strong and its visual impact intuitive, immediate and direct.

How do we begin to explore the mechanisms behind something like that? The sensation of wetness on your skin is certainly a very complex one, from a neuroscientific point of view, it requires the activation of at least two classes of receptors, one for temperature, the other for movement over the skin. Will we ever be able to get even close to that? Will touch through interfaces become possible when two people separated by miles?

As a neuroscientist, and as a man who is somehow hypnotized by the magic behind human senses, I am definitely thrilled about what we will learn in the future regarding the brain mechanisms responsible for body sensations, be they pain or pleasure! Alberto Gallace, section editor of this blog, is a cognitive neuroscientist with a special interest in the study of the mechanisms responsible for body-related sensations, pain and touch in particular.

He teaches at university of Milano-Bicocca, Psychobiology of human behaviour at both graduate and undergraduate level, and Neuropsychology of Pain at post-graduate level. He is also adjunct professor of Consumer Neuroscience, at commercial university Luigi Bocconi in Milan. His work underpins the very first model of tactile awareness and he is among the few researchers who have scientifically approached both the hedonic e.

Recently he co-authored with Charles Spence, a book on the theoretical and applied aspects of touch Gallace A and Spence, C, ; see below. Gallace A and Spence, C Listen to Lorimer Moseley talk to Karim Khan on new understanding of pain and focusing on the patient. We have active collaborations with editors scattered around the world. Together we are seeking a better understanding of the interaction between the body, brain and mind in chronic and complex pain disorders.

Body in Mind Research into the role of the brain and mind in chronic pain. Reference Gallace A and Spence, C Filed Under: Pain , Pain psychology , Research. Am I safe to move? Prof Paul Hodges on pain and altered movement. Understanding Pain. All blog posts should be attributed to their author, not to BodyInMind.

That is, BodyInMind wants authors to say what they really think, not what they think BodyInMind thinks they should think. Think about that! MotorImpairment Blog Joint position sense is unaffected during persistent experimental muscle pain Our ability to sense the position of our body, known as proprioception, is fundamental for controlling how we move and interact during daily activities Proske and Gandevia, People who have persistent pain i.

Around a third of critically ill patients require mechanical ventilation to help them breathe. While a lifesaving intervention, mechanical ventilation increases breathing and heart related complications, decreases quality of life, and costs at least an additional […].

Who are we?

Affective neuroscience aims to understand how affect pleasure or displeasure is created by brains. Progress is aided by recognizing that affect has both objective and subjective features. Those dual aspects reflect that affective reactions are generated by neural mechanisms, selected in evolution based on their real objective consequences for genetic fitness. We review evidence for neural representation of pleasure in the brain gained largely from neuroimaging studies , and evidence for the causal generation of pleasure gained largely from brain manipulation studies.

We suggest that representation and causation may actually reflect somewhat separable neuropsychological functions. Representation reaches an apex in limbic regions of prefrontal cortex, especially orbitofrontal cortex, influencing decisions and affective regulation.

Pleasure liking is especially generated by restricted hedonic hotspot circuits in nucleus accumbens and ventral pallidum. Affect, the hedonic quality of pleasure or displeasure, is what distinguishes emotion from other psychological processes. Affect therefore distinguishes affective neuroscience from other branches of neuroscience, and in a sense, all affective neuroscience could be viewed as a search for affect in the brain.

Yet to search for affect itself, as a core process of pleasure or displeasure, has rarely been the explicit goal of affective neuroscience studies. Consequently, the degree of understanding of how affect per se is created by brain mechanisms has remained relatively undeveloped even as brain studies of emotion have multiplied [ 1 ].

Yet fortunately, substantial progress has begun to be made in the past few years in understanding brain mechanisms of pleasure and displeasure [ 2 — 4 , 5 ].

We will focus here on the prototypical affect of pleasure as sensory reward. Pleasure and reward are important, both today and in evolutionary history.

Healthy well-being requires capacity for normal pleasure reactions. Dysfunction in reward circuitry can produce affective psychopathologies ranging from depression to addiction. Evolutionarily, selected pleasure reactions shaped behavior toward adaptive goals. Reward involves multiple neuropsychological components together: 1 the hedonic affect of pleasure itself liking ; 2 motivation to obtain the reward wanting or incentive salience ; and 3 reward-related learning.

Each component likely played key roles in optimizing the allocation of brain resources necessary for evolutionary survival, by helping to initiate, sustain and switch behavior adaptively among different available options [ 5 — 7 ].

Here, we concentrate on describing the progress made in uncovering brain mechanisms involved in liking or core pleasure reactions, but note that wanting and learning components involve overlapping neural systems. What is pleasure or core liking? First, pleasure is never merely a sensation.

Even a sensory pleasure such as a sweet taste requires the co-recruitment of additional specialized pleasure-generating neural circuitry to add the positive hedonic impact to the sweetness that elicits liking reactions described in details below [ 4 , 5 , 8 ]. Without that pleasure gloss, even a sweet sensation can remain neutral or actually become unpleasant. Second, pleasure has objective as well as subjective features. Pleasure mechanisms were selected and conserved by the same natural evolutionary pressures that shape any psychological function.

Hedonic mechanisms require millions of neurons arranged into patterns of mesocorticolimbic circuitry, a combination constituting substantial biological investment that was unlikely to have evolved if affective reactions did not convey significant objective benefits [ 3 , 9 — 11 ].

Darwin noted distinctive affective expressions facial, bodily and autonomic in humans and animals in various emotional situations. We similarly suggest that considering animal and human studies together allows the best progress to be made in understanding how affective reactions are mediated by brain systems.

Concerning human affect, it should be noted that objective liking -related reactions as well as subjective pleasure ratings liking in the ordinary sense can be measured in adults and infants. In adults, objective affective reactions alone, without any subjective feelings, can occur as unconscious pleasures under limited circumstances e. The translation of objective liking reaction into subjective pleasure feeling probably requires recruitment of additional brain mechanisms specialized for cognitive appraisal and conscious experience.

An implication of the objective-subjective distinction is that subjective ratings of felt pleasure, while crucial signatures of human affective experience, are interpretive readouts of underlying affective processes, not always infallible windows into core pleasure reactions themselves. Indeed, liking can sometimes occur unconsciously, and at other times even conscious pleasure ratings sometimes detach substantially from core affective reactions as people concoct explanations to themselves for how they think they should feel [ 16 — 19 ].

Therefore objective measures can be equally asuseful as subjective measures for probing pleasure and displeasure mechanisms.

Much of this circuitry is remarkably similar between humans and other mammals [ 20 — 22 ]. For example, essentially the same homologous region of deep ventral anterior cingulate cortex exists in both, but is called the subgenual anterior cingulate cortex Area 25 in humans, and called infralimbic cortex in rodents.

Hedonic hotspots and anatomical circuits that distinguish the nucleus accumbens hotspot in rostrodorsal medial shell as a unique site anatomy based on Thompson and Swanson TS symbol in orange boxes; and on Zahm and colleagues Z symbol in purple hexagons; Thompson and Swanson [ 66 ] reported that the nucleus accumbens hotspot of rostrodorsal medial shell is uniquely embedded in its own closed-circuit corticolimbicpallidal-thalamocortical loop, connecting discrete input subregions and output subregions, and segregated from other parallel loops passing through other regions of medial shell.

Zahm and colleagues suggested additional unique connections for the rostrodorsal hotspot [ 65 ]. GABAergic projections are indicated in red, hedonic hotspots are marked in yellow, glutamatergic projections are green, and dopaminergic projections are marked in blue.

Figure by Daniel Castro, modified from [ 81 ]. Still, some real differences do exist between limbic brains of humans and other animals.

Anatomically, encephalization also creates greater differentiation among prefrontal subregions. This may produce a few human cortex subregions that lack any clear homologue in nonprimates, such as dorsal anterior insula [ 23 ].

This may also produce some neuronal differences, such as the granular layer in anterior orbitofrontal cortex of humans that is missing in rats. Encephalization may also foster greater invasion by descending projections from prefrontal cortex into subcortical structures and functions. A possible human feature is greater freeway connectivity, or direct projections between cortex and deep subcortical structures. Psychologically, human encephalization may consequently result in a greater cortical involvement of affect and emotion, expressed as top-down regulation of affective reactions.

Still, mesocorticolimbic circuits for mediating core affective reactions are largely similar across all mammals. The sensory pleasure of a delicious-tasting food feels different from pleasures of sex or drugs. But does each psychological pleasure have its own neural circuit? Perhaps not. Instead there appears heavy overlap, with a shared mesocorticolimbic circuit or single common neural currency, involved in all those diverse pleasures [ 6 , 7 , 26 — 35 ]. Neuroimaging studies often implicate the same list of usual culprits as activated by various pleasures.

The list includes cortical regions e. This overlapping pattern opens the possibility that the same hedonic generating circuit, embedded in larger mesocorticolimbic systems, could give a pleasurable gloss to all such rewards even when the final experience of each seems otherwise unique. Subcortically, selective hedonic changes also may be tracked by neural firing in nucleus accumbens and ventral pallidum [ 38 — 41 ]. Such tracking gives the strongest evidence of pleasure representation because other nonhedonic features of the experience remain constant.

Subjective pleasure is faithfully coded by orbitofrontal cortex OFC activations in people. Pleasant sensations are also coded by activation in a medial strip of OFC green , but the medial strip may not as faithfully track changes in pleasure as the orange mid-anterior site [ 37 ].

Independently, posterior subregions of OFC represented complex or abstract reinforcers such as money whereas anterior subregions represented sensory rewards such as taste [ 82 ]. Some studies also indicate lateralization of affect representation, often as hemispheric differences in positive versus negative valence. The weight of evidence from research on causation of affect suggests that affective reactions may be generated chiefly in subcortical brain structures rather than by any of the cortical regions discussed above [ 3 , 46 ].

The other structures may represent affect as a step to generating their own different functions, such as cognitive appraisal, memory, decision making, etc. Evidence from humans that cortex is not needed to cause affect includes, for instance, persistence of relatively normal affective reactions such as pleasure even after massive damage to prefrontal cortex.

Despite pronounced memory and cognitive deficits, this patient retained a rich emotional life for 20 years as far as could be told, including remarkable capacity to talk about his feelings. He was also able to develop new Pavlovian learned fears of medical syringe needles and noisy fMRI machines and socially learned to prefer a friendly caretaker to a grumpy one. Affective reaction remaining despite prefrontal loss is one reason to suggest that cortical representation is a quite different function from subcortical causation of affect.

Studies in our laboratory have identified neural pleasure generators by focusing on the sensory pleasure of sweetness. Sweet liking is useful because affective facial expressions of taste pleasure liking exist in newborn humans and in some animals, aiding the objective measure of hedonic impact. For example, parents often know when their baby expresses a liking judgment of the deliciousness of a meal.

Sweet foods elicit a contented licking of the lips, but bitter tastes instead elicit disgust gapes and headshakes. Homologous liking orofacial expressions are elicited also in apes and monkeys, and even in rats and mice [ 47 ]. We have used brain manipulations of liking reactions to identify brain mechanisms that generate and enhance such pleasures as sweetness Figure 3.

Detail of hedonic hotspot in nucleus accumbens for pleasure generation sagittal view of medial shell and of neostriatum. By comparison, at caudal sites the same opioid microinjections only suppressed aversive disgust reactions to bitter quinine purple; e. Modified from [ 81 ], based on data from [ 51 ]. When amplified by addictive drugs or by endogenous factors, dopamine helps generate intense levels of wanting, characteristic of drug addiction, eating disorders, and related compulsive pursuits [ 44 , 53 , 58 — 60 , 61 ].

Why, then, are dopamine-promoting drugs such as cocaine or methamphetamine reportedly so pleasant? For instance, there is evidence to suggest that elevation of endogenous opioid signals may be recruited in limbic structure [ 62 , 63 ]. Such opioid recruitment in accumbens-pallidal hotspots described below would plausibly generate pleasure liking [ 64 ]. We have identified several pleasure generators as small hedonic hotspots, nestled in subcortical structures [ 48 — And in the anterior half of ventral pallidum, DAMGO microinjection actually causes opposite suppression of liking reactions.

So far, no hedonic hotspots have yet been found in neocortex though the search continues , but rather only in these subcortical structures. Continued failure to find a hedonic-enhancing hotspot in prefrontal cortex would be another reason to distinguish between cortical representation and subcortical causation of pleasure as different functions. Each accumbens-pallidum hotspot is only a cubic-millimeter in volume in rats a human hotspot equivalent should be approximately a cubic-centimeter, if scaled to whole-brain size.

Functionally, hedonic hotspots seem quite specialized for intense pleasure generation compared to regions around them.

Neurobiologically, hotspots may have unique anatomical or neurobiological features that distinguish them from the rest of their containing structure, and which perhaps permit the functional specialization for pleasure causation [ 65 — 67 ] Figure 1. Rather opioid stimulation has the special capacity to enhance liking only if the stimulation occurs within an anatomical hotspot — whereas dopamine never does anywhere [ 48 , 68 , 69 ]. Beyond NAc and ventral pallidum, opioid stimulation in all regions tested so far for other structures, such as neostriatum, amygdala, etc.

Overall, the pattern indicates strong localization of hedonic function, as well as neurochemical specificity of pleasure neurotransmitters. Functionally, hotspots in nucleus accumbens and ventral pallidum interact together in a single integrated circuit.

The two sites act as a functional unit for mediating pleasure enhancements [ 48 , 72 ]. Each hotspot seems able to recruit the other to unanimously generate amplification of liking. For example, a single opioid microinjection into the NAc hotspot enhances also responsiveness of ventral pallidum hotspot neurons, reflected in neuronal firing patterns elicited by a sweet taste or in gene activation, at the same time as enhancing behavioral liking reactions [ 48 , 72 ]. Unanimous recruitment of both hotspots further appears to be required to magnify pleasure.

Finally, the ventral pallidum hotspot may be especially important for maintaining normal levelsof pleasure. Damage to ventral pallidum can cause even sweet sucrose taste to elicit purely negative gapes and other disgust reactions for days or weeks afterwards [ 8 , 73 , 74 ].

Brain mechanisms for pain and pleasure