Pleasure Gone Awry? A New Conceptualizationof Chronic Pain and Addiction

Valerie Gray Hardcastle

Published online: 29 December 2013# Springer Science+Business Media Dordrecht 2013

Abstract I examine what happens in the brain when patients experience chronic painand when subjects are addicted to alcohol. We can find important parallels betweenthese two cases, and these parallels can perhaps point us toward new ways of treating(or at least understanding) both issues. Interestingly, we can understand both cases asour pleasure system gone awry. In brief, I argue that chronic pain and alcohol addictionboth stem from a dysregulation in our brain’s reward structure. This dysregulation inwhat should be our pleasure circuitry pushes individuals to behave in ways counter-productive to their needs and to feel unpleasant things. In other words, there is likelyboth something quite right and perhaps quite wrong about how some philosophers arethinking about pain as an evaluative state. I shall be arguing that pain is both hedonicand evaluative, though perhaps not in the ways they are imagining.

Think about consuming something you like. For the most part, we think of thatexperience as something pleasant. Yet, if we over-consume, that pleasant experiencecan quickly turn awful. We become bloated, or hung-over, or anxious, or jittery. Thesevery basic events hint to us that there is something similar about good and badexperiences, about pleasure and pain. Things can feel good, until they just don’tanymore. What is it about us that provokes that switch? And if we can understand thatswitch, would we thereby understand something new about pain?

In a perhaps oblique way, this essay looks at these general questions. I concernmyself not so much with pleasure per se, but with what happens in the brain whenpleasure gives way to awfulness and when that awfulness does not go away. Inparticular, I examine what happens in the brain when patients experience chronic painand when subjects are addicted to alcohol. I believe that we can find important parallelsbetween these two cases, and these parallels can perhaps point us toward new ways oftreating (or at least understanding) both issues. Interestingly, we can understand bothcases as our pleasure system gone awry.

Rev.Phil.Psych. (2014) 5:71–85DOI 10.1007/s13164-013-0170-3

V. G. Hardcastle (*)Philosophy, Psychology, and Psychiatry & Behavioral Neuroscience, University of Cincinnati,Cincinnati, OH, USAe-mail: valerie.hardcastle@uc.edu

Right now, even though we do know a lot about pain processing in the brain, as wellas how addiction manifests itself, we still have effectively no good treatments for eitheraffliction. This sad fact has huge ramifications for our societies. Chronic pain affectsapproximately 116 million American adults annually and costs the United States up to$635 billion dollars are year in (largely ineffective) health care and lost wages.(Committee on Advancing Pain Research, Care, and Education, Institute of Medicine2011). In addition, about 18 million Americans suffer from alcohol abuse or depen-dence, contributing to 100,00 deaths annually and costing about $185 billion (Grantet al. 2004). Clearly, it is important to get it right when treating both chronic pain andaddiction. And this means that we need to understand what these things are.

In this essay, I am going to suggest that a new approach to both disorders couldprove fruitful, an approach that unites both afflictions as members in the same family ofillness. In brief, I shall be arguing that chronic pain and alcohol addiction both stemfrom a dysregulation in our brain’s reward structure. This dysregulation in what shouldbe our pleasure circuitry pushes individuals to behave in ways counter-productive totheir needs and to feel unpleasant things.

What I shall be urging is that there is an underlying structural commonality betweenchronic pain and addiction. This commonality could form the foundation for a newtheoretical approach to understanding these conditions, as well as perhaps a new way ofunderstanding normal acute pain as an instance of a type of pleasure (namely, thepleasure of relief). My claim is that chronic pain, addiction, and probably otherpsychological processes or states are all part of the same species of disorder, and theyare all tied to a perversion in our motivations. In other words, there is likely bothsomething quite right and perhaps quite wrong about how some philosophers arethinking about pain as an evaluative state (e.g., Bain 2011; Bain 2014; Bain 2014;Helm 2002). I shall be arguing that pain is both hedonic and evaluative, as is pleasure,though perhaps not in the ways they are imagining.

1 Preliminaries: DSM, NIMH, and Bottom-up Neuroscience

The latest version of the American Psychiatric Association’s Diagnostic and StatisticalManual for Mental Disorders, the DSM-5, was just published in spring of 2013. Likeall the previous versions, it outlines criteria by which practitioners in the United Statesand Canada describe and classify mental disorders. While the DSM does standardizediagnostic categories and criteria, it also attracts considerable criticism. Detractorsargue that the manual promotes invalid categories that rely on superficial symptomsand that it medicalizes political, cultural, and insurance companies’ interests and biases.Most notably, a number of experts criticized the DSM-5 heavily before it was evenpublished, arguing, among other things, that its criteria did not reflect the best (or any)that science had to offer.

Dr. Thomas Insel, Director of the National Institute for Mental Health (NIMH),wrote in his blog on in the NIMH site shortly before the publication date:

While DSM has been described as a ‘Bible’ for the field, it is, at best, a dictionary,creating a set of labels and defining each. The strength of each of the editions ofDSM has been ‘reliability’ – each edition has ensured that clinicians use the same

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terms in the same ways. The weakness is its lack of validity. Unlike ourdefinitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnosesare based on a consensus about clusters of clinical symptoms, not any objectivelaboratory measure. In the rest of medicine, this would be equivalent to creatingdiagnostic systems based on the nature of chest pain or the quality of fever.Indeed, symptom-based diagnosis, once common in other areas of medicine, hasbeen largely replaced in the past half-century as we have understood thatsymptoms alone rarely indicate the best choice of treatment. Patients with mentaldisorders deserve better. (2013)

He concludes by indicating that, for research purposes, the NIMH will be replacingthe DSM with “Research Domain Criteria,” which define mental disorders based notjust on vague lists of symptoms but on more specific, underlying, genetic, neural andcognitive data. He wants to start with our best understanding of brain science and thento link that to clinical behavioral data. In other words, he is advocating for a bottom-upapproach to mental disorders; he wants to try to understand what is going on with thebrain without first assuming psychological categories, which can be misleading.

Such work has already begun. In her long career researching schizophrenia, CarolTamminga had noticed that schizophrenia and bipolar disorder often co-occur(Tamminga 2013). Over a fourth of schizophrenia patients also are diagnosed withbipolar disorder, and about a third of bipolar patients are also diagnosed with schizo-phrenia. She also discovered, much to her chagrin, that psychological and biologicalphenotypes associated with schizophrenia and bipolar disorder (e.g., stop-signal errorrates and latency measures, distinctive EEG and ERP patterns) do not cluster accordingto the DSM categories. That is, the patients whose behavioral and biological measuresare most similar do not group into their psychiatric diagnoses, as one would perhapsexpect. Interestingly, however, they do cluster in statistically significant ways into threeother groups (which she helpfully has labeled Biotype-1, Biotype-2, and Biotype-3),and these biotype groups show noteworthy differences across measures of cognitivecontrol functions and sensorimotor interactions. She is starting to ask whether theremight be a better way to carve up the diagnostic space of schizophrenia, schizoaffectivedisorder, bipolar disorder, and psychosis that more accurately reflects both the under-lying biology of patients with these syndromes and their on-going symptoms.

While it is much too early to tell whether Tamminga’s new groupings are the correctones, the scientific process she has followed is one I aim to emulate in this essay. Westart at the bottom, without our normal psychological categories to guide us, to seewhether we end upwith different way of carving Nature at her proverbial joints. In manyrespects, we can see analogies between the controversies with the DSM criteria andneuroscientists (and others!) who rely on some version of belief-desire psychology to tryto understand complex brain functions that in fact may not map at all well onto thesecategories. In what follows, I try to flesh out this analogy. I attempt to build an approachfrom the bottom up, looking at what the brain is doing under both conditions, withoutrelying too heavily on what our intuitions tell us about the phenomenology of pain oraddiction or about what is important about either. At the end, I will close with somegeneral comments about the viability of reducing mental categories to neural ones.

But before I launch into a description of this new approach, I want to be clear aboutthe line I will ultimately be pushing. I am not claiming that chronic pain and addiction

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are the same things. Rather, I want to claim that both of these conditions have verysimilar underlying neurophysiology, and because of that fact, it might make sense tothink of these two disorders as being of a conceptual piece. This is a strategy similar toone being used in other areas of biology; for example, it is currently reflected in on-going discussions regarding what is known as pathogenic protein seeding (Jucker andWalker 2011; Polymenidou and Cleveland 2012; Walker and Jucker 2013).

Scientists are beginning to see structural and etiological similarities amongCreutzfeldt-Jakob disease (or mad-cow disease), Alzheimer’s, Parkinson’s,Huntington’s, amyotrophic lateral sclerosis (ASL or Lou Gehrig’s disease),concussion-related dementia, multisystem proteinopathy, and some amyloidosis.What do all these disparate diseases have in common? It appears that, in each case,the disease occurs because an errant protein misfolds in such a way that it causes otherlike proteins around it to fold in the same errant way and then to clump together in amass. A chain reaction of misfolding and clumping, called “pathogenic proteinseeding,” ensues, and we end up with brains that are plaqued or tangled or destroyed.

While researchers are not claiming that all these diseases are the same thing, they aretentatively coming to the conclusion that abnormally folded proteins that seed otherproteins to behave in a similar manner explains the origin of each one of these illnesses.The ultimate hope is that this united conceptual framework will permit similar treat-ments or cures for a whole host of neurodegenerative diseases. All these diseases arepart of the same family.

Similarly, I believe that chronic pain and addiction result from similar types ofmalfunctions of a particular set of brain circuits, that there is a fundamental underlyingneurobiological unity between chronic pain and addiction. Crucially, this is not arelationship that one can see if one focuses on DSM criteria or other psychological orbehavioral symptoms as the defining characteristics of these disorders. You can onlysee this if you start at the bottom, as it were, and build up.

Why might one believe that the line I am suggesting is a fruitful approach to take inunderstanding pain or addiction? Let me spend a few minutes outlining the psycho-logical and behavioral connections between pain and alcohol consumption.

Many of us know through experience that ingesting alcohol reduces pain sensation,just as it reduces our sensations of touch. Why should this be the case? Actually whatreally happens is we get analgesia with alcohol consumption, followed by an increasein pain sensitivity (hyperalgesia) as the body withdraws from alcohol (Gatch 2009;Jochum et al. 2010). These connections between alcohol and pain sensitivity suggestthat there must be some neural systems in common between substance reinforcementand pain transmission.

In addition, problem drinkers are more likely to report pain and exhibit greatersensitivity to painful conditions than purely social drinkers (Brennan et al. 2005;Castillo et al. 2006; Holmes et al. 2010). In fact, alcoholism and alcohol abuse canaccurately predict a patients’ clinical ranking of pain severity following injury. Andthose using alcohol to treat chronic pain showed worsening of drinking and otherhealth-related problems, suggesting that the analgesic effects alcohol contribute toabuse (Brennan et al. 2005; Riley and King 2009; Weissman and Haddox 1989).Many have concluded that pain sensitivity, and the patterns of analgesia andhyperalgesia associated with alcohol consumption and withdrawal, contribute to alco-hol addiction (Egli et al. 2012).

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Moreover, alcoholics and those with a history of binge drinking feel greater painrelief from alcohol than control subjects and non-binge drinkers (Brown and Cutter1977; see also Stewart et al. 1995). Most importantly, perhaps, not only do we findclear positive associations between alcohol dependence and pain sensitivity, but wealso see these same associations with family members of those with drinking problems.That is, subjects who have alcoholic relatives, even though they themselves are notalcoholic, rank stimuli as more painful than do subjects for whom alcoholism is not partof their family tree. Similarly, patients with chronic pain conditions are morelikely to have family members who are alcoholics than those who do not(Katon et al. 1985; Goldberg et al. 1999). It appears that whatever genetic orenvironmental factors promote alcoholism in family members are linked with(or are identical to) the genetic or environmental factors that support chronicpain conditions.

Other conditions associated with chronic pain include depression and anxiety,which tell us that whatever changes in pain processing that lead to chronic painare likely related to or influence the so-called fear circuit, which underliesanxiety disorders. This basic circuit is also involved in substance abuse andaddiction. The fear circuit in the brain is what associates a negative valencewith some event or thing. It includes the medial prefrontal cortex (mPFC),which engages in planning and setting goals; the amygdala, which is ouremotional center; and the hippocampus, which records the “what” and “where”of events, things, and activities. The mPFC normally suppresses amygdalaactivation. As I will discuss below, in chronic pain patients, this route ofinfluence is reversed, and in those patients, their amygdala inhibits the mPFC.We see the same sort of reversal in anxiety disorders. This leads us to concludethat the neural substrates underlying pain, alcoholism, and emotions shouldoverlap one another.

As a preview of things to come, I should mention that the fear systemoverlaps neurobiologically with our pleasure or reward system, and both arecomponents of our basic limbic system. In particular, the amygdala and theprefrontal cortex function in both systems to support conditioned learning andmemory as well as to regulate our emotional reactions (cf. Feder et al. 2009).More generally, the components that make up our limbic system are highlyinterconnected and function most of the time as an integrated whole, though awhole comprised of identifiable parallel circuits.

2 The Neurobiology of Pain

Historically, pain processing has been divided into two basic components, the affective-motivational processing stream and the sensory-discriminatory processing stream. Thisdivision goes back to Sir Charles Scott Sharrington’s and Sir Henry Head’s work on thefunction of neurons and the somatosensory system in the early 1900s (Sherrington1906; Head and Holmes 1911). The fundamental importance of this division wasunderscored in the 1960s, as neuroscientists discovered two different spinothalamictracts involved in nociception, a medial pathway involved in processing affect and alateral pathway involved in sensory encoding.

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This division lives on today, largely as an assumed and unexamined truth. Here is afairly typical description of nociception from a contemporary on-line textbook chapter:

The body is equipped with mechanical nociceptors at the periphery (so-calledfirst-order neurons), which project to second-order neurons in the spinal cord andmedulla, which then carries the sensory information (in the form of electricalimpulse) to the thalamus, where it synapses with third-order neurons that transmitthe impulse to the cortex.

Second-order neurons send their sensory inputs to the thalamus via two ascendingpathways: the dorsal column medial-lemniscal system and the anterolateralsystem ([which] includes the spinothalamic, spinoreticular, and spinotectal fi-bers). The former transmits impulse involving position sense, touch, and pressure.The latter pathway is involved in [the experience of] pain transmission (Jensenand Karoly 1987 [sic]).

The spinal cord is the central concourse along which all pain messages travels toand from the brain (Catalano 1987). For example, when you stub your toe andyour peripheral nerves register alarm, this acute pain is immediately relayed alongthe nerve fibers of your foot and leg to the substantia gelatinosa located within thedorsal horn of the spinal cord. The cells in the substantia gelatinosa relay this“fast pain” message along the neospinothalamic and terminating in the thalamusand the cortex … (Catalano 1987). The cortex is the region in which [sensoryinformation, e.g., location, intensity, and duration information] is… processed.

In contrast, [“slow’]… pain moves along a different and slower tract, called thepaleospinothalamic tract. This … pain is generally dull, aching, burning, andcramping (Catalano 1987). Slow pain follows the same path as the fast painthrough the spinal cord, but once in the brain, it separates and terminates in thehypothalamus and the limbic structures (Catalano 1987). The hypothalamus isresponsible for stimulating the release of stress hormones. The limbic structuresare the places where emotions are processed. (Yang 2013)

My point is that a two-dimensional structure for pain is widely assumed andubiquitous in the literature, including philosophical perspectives (e.g., Aydede 2006).But more significantly, since hypothesis was put forth in the 1960s, scientists have notmade much progress in uncovering the details of its operations. Indeed, as Apkarianmaintains, evidence for division remains “fairly weak” (2012, p. 6).

There are four basic evidentiary challenges to providing support for the hypothesis.First is that there is a lot of crosstalk in our nervous system, starting in the spinal tractsand continuing on up through cortex (Giesler et al. 1981). Such crosstalk prevents anyparticular area from being either just affective or sensory but suggests that various areasin the spine and brain process both types of information together. Second, verbalreports (or other behavioral indicators) of pain intensity and the magnitude of pain’sunpleasantness are tightly correlated, which makes differentiating the two in terms ofbehavioral markers very difficult. But if we cannot distinguish between subjects’intensity ratings and their unpleasantness ratings, then we lose any claim to their beingdistinct and separable psychological entities. Third, and perhaps most unfortunatelyfrom my perspective, many neuroscientists simply assign the tag “affective” or

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“sensory” to brain regions depending on whether it received projections from the lateralthalamic regions or the medial thalamic regions. By adopting previous neurophysio-logical and psychological distinctions without serious reflection, these neuroscientistsonly serve to reify what might in fact be a false dichotomy. And finally fourth, there aresome brain regions, like the insula, that just do not clearly fall into either type ofprocessing circuit (more on this below) (Apkarian 2012).

Let us take a different approach to understanding the neurophysiology of painprocessing; let us take the perspective of our pain system being a system of motivation.We can see this sort of perspective in pain researchers such as Vania Apkarian, GeorgeKoob, and Giandomenico Iannetti as well as in philosophical treatments like DavidBain’s. The basic idea is that normal acute pain, which normally signals tissue damage,first prompts us to escape or avoid our current situation in order to minimize physicalharm and then, when the pain stops, provides us with a sense of relief. Together, thesetwo reactions – avoidance and the feeling of relief – not only protect our bodies, butthey also contribute to our being able to predict the utility and costs of competingbehavioral goals. That is, when we are confronted with a conflict between a potentialthreat and a potential reward, we have learned from past pain experience how toevaluate the severity of the threat.

One consequence of adopting this perspective on pain processing is that removes, orat least seriously diminishes, the strong distinction we assume between our folk notionsof pain and pleasure. Our folk intuition is that pain is unpleasurable and pleasure is,well, pleasurable. But if our pain system works because it gives us a sense of relief,then it too could be considered, perhaps, part of our pleasure-inducing systems. Thepain motivates us to do something, not just because it hurts, but also because when wesuccessfully do the something required to stop the pain, we feel more than the absenceof pain. We also feel pleasure. I do not want to push too hard on this analysis, since Ihave never really believed that we should give much credence to our workadayintuitions, but I do want to highlight what this new perspective might imply for whatthe folk (or what philosophers think the folk) believe.

A second consequence of adopting this perspective is that it denies that there is abrain circuit specific to pain processing (Iannetti and Mouraux 2010). Pain processingis simply part of our on-going risk-reward calculations. Contrary to popular theorizing,there just is no such thing as a dedicated “pain matrix” (see, e.g., Ploghaus et al. 1999;Ingvar 1999; Brooks and Tracey 2005). Indeed, it might turn out that Melzack’s (1989)original idea for a non-specific neuromatrix, a widely distributed network of neuronsthat crosses many areas of the brain and underlies pain perception, might be correctafter all. We have one reward calculator, as it were, and one component of thiscalculator is what we normally take to be pain processing.

One specific hypothesis regarding how this type of system might work in the brain isthat the insula integrates magnitude information regarding pain, which then feeds thosecalculations to the nucleus accumbens (NAc). The NAc indexes our anticipation of painand calculates the reward value of pain relief by integrating the magnitude informationfrom insula. It then feeds its estimation to other limbic areas involved in analyzingrewards. These areas talk to our cortex, which concerns itself with planning andpromoting actions (Cauda et al. 2011). This process, incidentally, is the sameprocess our brains go through when we seeking some intuitively pleasurableoutcome as well.

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Let us look closer at the insula and perceptions of pain intensity. If there are no braincircuits specific to pain processing, then the insula should index the magnitude of otherthings, along with pain. And this is exactly what scientists are finding. In a recent study,researchers recorded the fRMI BOLD signals from the insula as subjects rated theirperceived magnitude of thermal pain stimuli (Baliki et al. 2009). They discovered thatfor each episode of perceived pain, the magnitude of the peak pain rating was correlatedwith the peak fMRI insular activity. Importantly, they showed almost identical effectsfor subjects estimating the length of visual stimuli. Other studies have shown thatnociceptive, somatosensory, auditory, and visual stimuli all cause virtually indistin-guishable responses in the insula, primary and secondary somatosensory cortex, as wellas in the anterior cingulate cortex (Iannetti et al. 2010). Unlike auditory or visualstimuli, which cause specific sensory response in primary auditory or primary visualcortex, nociceptive inputs do not seem to elicit any specific nociceptive responses.

Once we get away from dividing pain into affective and sensory components, wemake room for a new way of looking at nociceptive and pain processing data and canuncover different response and activity patterns. For example, Apkarian’s lab has foundparticular temporal sequences that correspond to anticipating a painful stimulus, theperception of the pain itself, and relief after the pain is over (Baliki et al. 2010). Theaforementioned NAc and the anterior portion of the insula are most active just at thestart of a thermal painful stimulus. But when subjects indicated that they actually feltpain, these regions quieted and the posterior portion of the insula and the anteriorcingulate became the most active. Finally, as the stimulus was returning to baseline, theperi-acquiductal gray region became active and the posterior insula and anteriorcingulate returned to baseline as well. We can identify three distinct and differentnetworks that are sequentially activated during acute pain processing.

Moreover, all of these regions are part of our motivational system that calculates andexperiences risk and rewards. As a preview regarding what is to come, I note thatalcoholism and addiction also show similar tripartite pattern. But first, a quickdiscussion regarding the similarities and differences between acute pain andchronic pain will help elucidate why chronic pain should be considered adisorder of motivation and reward.

3 From Acute Pain to Chronic Pain

One might intuitively believe that chronic pain is just an acute pain that does not goaway. This actually is far from the truth. We can actually have acute pains that last andlast, and these are different from chronic pains that last and last. Chronic pain isrepresented in different areas in the brain than acute pain, because, as it turns out, thebrain reorganizes itself when it is in chronic pain.

For example, as discussed above, the insula indexes acute thermal pain, and yetactivity in the medial prefrontal cortex (mPFC) is best correlated with outbreaks ofspontaneous (chronic) back pain. Interestingly, when back pain patients experience anacute pain, such as a thermal stimulus, their insula lights up just as normal subjects’would under similar conditions (Baliki et al. 2006). To make matters more complicated,we find different regions of brain activity associated with different types of chronicpain: in post-herpetic neuralgia, to take one example, the amygdala is most active

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during spontaneous pain, instead of mPFC. The point is that there are few, if any, brainareas activated in common across all chronic pain conditions and in acute pain – furtherevidence that there is no fixed “pain matrix” in the brain.

But both the amygdala and the mPFC are part of the limbic system, so it appearsperhaps that the differences in activation in different types of chronic pain are differ-ences in emphasis within the same network, as opposed to activations in entirelydifferent networks, which is what we might be seeing when we contrast acute painwith chronic pain. Even though different types of chronic pain engage distinct corticaland subcortical regions, we can still discern overarching activity patterns. Most types ofchronic pain shift away from what might be referred to as simple nociceptive process-ing to more affective and motivational reactions. Moreover, the nearly continuousactivation of these areas has specific on-going effects: the baseline level of activity inthe insula and anterior cingulate is much higher in chronic pain patients than in controlsubjects. Such is not the case for other areas of the brain, like the sensory cortices(Malinen et al. 2010).

One hypothesis is that the near continuous activation of the limbic areas shiftsreward valuation, and these shifts in turn modulate learning and memory (Apkarian2012). In other words, being in chronic pain fundamentally changes how one thinks,learns, remembers, and feels. There is some neurophysiological evidence for this idea.As suggested by the data above regarding activity correlations with spontaneous pain,how the NAc is connected to the rest of the brain is different for chronic pain patientsthan healthy subjects. Moreover, this change in connectivity is tightly correlated withthe magnitude of back pain reported by the chronic pain patients. In normal subjects,the NAc and the insula are highly interconnected. But in chronic pain patients, the NAcshifts its functional connectivity to mPFC. That is, in normal subjects, when the NAclights up, the insula do as well, but in chronic pain patients, when the NAc is activated,mPFC responds (Baliki et al. 2010). And, the more spontaneous pain the patients feel,the stronger the correlation between activity in NAc and mPFC.

As a result of this rewiring, NAc activity differs between healthy subjects andchronic pain patients for instances of acute pain, especially during the “relief” phaseof pain processing. Normal subjects’ brain activity signals that a reward is coming quitereliably, but chronic pain patients’ brain show activity that reflects a lack of predictedreward and even perhaps disappointment. Normal subjects should be happy andrelieved that their pain is ending, but chronic pain patients would still have theirchronic pain when the acute pain stimuli ends. Indeed, quite often an acute painrelieves or at least covers over the chronic pain. Under those circumstances, the chronicpain patient should be sad that the acute pain is ending.

This change in brain connectivity is a functional rewriting not specific to painprocessing, for we see similar effects for monetary rewards in chronic pain patients –their brains show no real response to reward or loss (Apkarian 2012). In other words,chronic pain puts stress on our protective and adaptive motivational systems such thatour motivational system fundamentally changes how it operates. And this change infunctionality is so large that it distinguishes between normal subjects and chronic painpatients with an accuracy of more than 90 % (Baliki et al. 2010).

These results are even more remarkable because they are independent of subjectivepain perception. The distorted brain responses are not reflected in the conscious painratings by chronic pain patients. They are unaware of any impact their pain sensations

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have on their motivations, sense of disappointment or relief, or anticipated rewards.Therefore, the effect we are seeing is an unconscious effect by the brain that influencesactions, decisions, and feelings.

Vania Apkarian hypothesizes that nociceptive information impacts the limbic system(including the hippocampus, the NAc, and the amygdala). The limbic system, in itsinteractions with the prefrontal cortex, determines when a pain condition morphs into amore emotional and chronic state. The activity in the limbic system also modulates therest of the cortex such that we get the functional and anatomical distortions seen inchronic pain conditions. He concludes that chronic pain is a disorder of our motiva-tional/affective system. However, even if Apkarian is wrong in the details of his model,the evidence surrounding chronic pain processing does support the conclusion that it isintimately tied to our reward circuitry.

4 The Neurobiology of Addiction

Let us now turn out attention to alcoholism and addiction. Substances of abuse inaddicts are thought to usurp systems in the brain that normally direct mammals tostimuli salient for their preservation or flourishing. Most hypotheses regarding theneurobiology of addiction have as a common element a narrowing of the addicts’focus to drug-seeking behaviors at the expense of natural rewards. In other words,addicts lose their sense of pleasure for many of the things that we normally andintrinsically find happy-making (food, sex, comfort, success) as their desire for thesubstances of choice grows.

Addiction is normally seen as a behavioral control disorder. Many contemporarytreatments of addiction identify both impulse control difficulties as well as compulsivebehaviors. Patients with impulse control disorders feel an increasing sense of tension orarousal before committing an impulsive act, and then pleasure, gratification, or a senseof relief at the time of doing the act itself. These types of disorders are generallyassociated with positive reinforcement mechanisms (American Psychiatric Association2013). In contrast, patients with compulsive disorders feel anxiety and stress beforeengaging in some compulsive behavior, and then a sudden release from the stress asthey perform the compulsive behavior. Their disorders are associated with negativereinforcement mechanisms. (Already, we can see interesting comparisons with painprocessing, which is associated with positive reinforcement at the cessation of acutepain sensations in normal subjects, but not in the case of chronic pain patients.)

Putting impulsivity and compulsivity together gives us the three stages of the self-reinforcing cycle of addiction: binge or intoxication, withdrawal, and preoccupationand anticipation. Impulsivity often dominates early in addiction, and impulsivitycombined with compulsivity dominates later in the disease. As addicts move fromimpulsivity to compulsivity, the driving force motivating their addictive behaviorsshifts from pleasure and positive reinforcement over to anxiety, stress, and negativereinforcement (Koob and Le Moal 2001; Edwards and Koob 2010).

The transition from normal alcohol consumption to genuine alcohol dependenceinvolves circuitry in the forebrain, including the amygdala and prefrontal cortex (Gilpinand Koob 2008). Similar areas are involved in the transition from acute pain processingto a chronic pain syndrome. Let us examine the different areas of the brain relevant to

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addiction to understand their relation to what we have seen with pain processing,starting with the insula, an area we know is relevant for processing the magnitude ofpainful stimuli.

The insula, particularly its more anterior regions, is reciprocally connected to severallimbic regions (the mPFC, amygdala, and striatum, for example) and, as we have seen,appears to integrate information regarding the magnitude of sensory inputs withemotion or motivation, often leading to (or underlying) conscious experiences of pain,and, in this case, addictive urges (Bechara and Naqvi 2009). Indeed, brain lesionstudies suggest that the mPFC and insula are necessary components of the brain circuitsunderlying affective decision-making (Clark et al. 2008). Smokers with damage to theirinsula, for example, are able to stop smoking easily and without experiencing eithercravings or relapse (Naqvi et al. 2007). This is not the case for smokers with lesionsoutside the insula. Just as this area is being used as a biomarker for pain intensity, itcould perhaps also be a biomarker to help predict addictive urges.

There are additional circuitry overlaps between pain processing and addiction in theNAc, amydala, and PFC. We already know that the NAc encodes everything fromsalience to reward to aversion. We believe that the NAc may mediate the reward valueof pain relief, as we see decreases in NAc activity to acute painful stimuli in normalsubjects but increases with chronic pain patients. Similar to the changes in connectivityof NAc to other areas we see in chronic pain patients, addicts also show increasedconnectivity to the mPFC, which might contribute to increased reinforcement of drugsand alcohol in addiction.

Nociceptive pathways terminate in the amygdala, which, as part of the limbicsystem, processes the emotional aspects of pain. Amygdala activity is increased inchronic pain patients, which might lead to increased negative reinforcement of painfulexperiences. The amygdala is also connected to processing salience or reinforcement inalcoholics, in much the same way as in chronic pain patients.

Activation in the amygdala in chronic pain patients also indexes changes in mPFC.We see similar patterns in alcoholics. Changes in addicts’ PFC likely impair theirdecision-making, which then can lead to increased alcohol dependence. This area isvery involved in drug-seeking and other compulsive behaviors. (Though not discussedin this essay, we also find cognitive deficits in chronic pain patients, which often affectstheir choices for pain management.) Just as we can tie functional connectivity with themPFC to whether a subject has chronic pain, we can also connect similar changes topropensity for relapse in a putative addict. In short, we find a significant intersection ofthe neural substrates for chronic pain processing and for alcohol dependence.

While I have only discussed the similarities between chronic pain patients andalcoholics, we could probably tell the same story for chronic pain patients and heroinaddicts, for opioids and alcohol activate similar neural circuitry in similar ways(Modesto-Lowe and Fritz 2005; Gianoulakis 2009; Egli et al. 2012). But I am notcertain that this story would generalize much beyond that, for already evidence isaccumulating that pain processing is not associated with the effects of cocaine addictionon brain circuitry, for example (Edwards et al. 2012; Ewan and Martin 2011). Why wesee these differences in interaction effects between pain and different types of addic-tions is not yet clear, because cocaine, alcohol, and heroin all activate the dopaminergicsystem in the NAc and amydala (though they do each have other individual effectselsewhere in the brain). There is going to be more to the story than the simple sketch I

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have laid out here, but I am hopeful that I have outlined useful first steps in a new wayto conceptualize pain processing and addiction as two potential consequences of adysregulated reward system.

5 Conclusions

David Bain argues that “being in unpleasant pain consists in (i) undergoing a somato-sensory experience that represents (accurately or inaccurately) that a part of one’s ownbody is damaged or under threat of damage; and (ii) that experience additionallyrepresenting the damage or threat as bad” (2014, italics his). I would add to hischaracterization that the brain unites “bad” experiences with motivations to do some-thing, to get rid of the bad thing. The whole complex of the somatosensory experience,the representation of badness, and the affective motivation comprises pain, of which theconscious experience of “ouch” is only a part. And this complex is not specific for pain,but it is perhaps a reflection of how the brain processes all incoming stimuli. In otherwords, I am suggesting here that chronic pain, addiction, (and perhaps other disorders)as well seeking pleasurable experiences, are all effects of our basic reward circuitry inthe brain. Both chronic pain processing and extended episodes of alcohol intoxicationand withdrawal change brain circuitry and functionality in similar ways, with similareffects. If the approach I am advocating for here is correct, then knowing this fact mightlead to improvements in clinical descriptions of important disorders, which then mightlead to better therapeutic treatments. It also might help us understand when and whypleasurable activities stop being such, even as the activities themselves remain the same.

But my larger point is that it is probably a mistake for neuroscientists to adoptpsychology’s or psychiatry’s “natural kinds” without reflection, as they have histori-cally done. A better, and likely more productive, research approach would be for themto build up their own theories from neurobiological perspective, and then to see howthese hypotheses and theories dove-tail (or not) with what psychology and psychiatryhold true. While this approach might be seen as a variant of Patricia Churchland’snotion of “reductive co-evolution” (1986), I am also suggesting that it might be moreuseful for neuroscience to be willing to stand apart from the other behavioral andbiological sciences.

Neuroscience has a history that goes back at least until David Marr (1982) of beingseen as the implementer of our cognitive engines. It was therefore not perceived as adiscipline that could contribute substantively to theoretical advances about cognition orpsychological function. I believe that recent work in the neurosciences is proving thisold conception incorrect. Not only can neuroscience offer a unique theoretical perspec-tive on mind and brain function, but also what it offers could help solve some long-standing difficulties with psychological and psychiatric approaches. It is at least worthletting neuroscience take the lead in developing theories for a while, especially giventhe lack of progress we have seen in psychiatry and clinical psychology in managing ortreating some of our most common mental ailments.

It might be the case that, at the end of the day, psychiatry and psychology keep thebehaviorally defined categories of “pleasure,” “pain,” and “addiction,” but that neuro-science parses its domain very differently, speaking of generic affective-reward circuitsinstead. And each domain might intervene in their respective systems differently, based

82 V.G. Hardcastle

on how they have defined their categories. Psychiatrists might still prescribe antabuse(disulfiram) to prevent alcoholics from drinking again, and analgesics with SSRI’s orSNRI’s for chronic pain patients, hoping to relieve their discomfort while tampingdown their anxiety, while psychologists could engage with addicts in counselingsessions designed to uncover their emotional triggers for abusing substances and withchronic pain patients in behavioral-modification therapy to help them live pain-freelives behaviorally (which does, interestingly enough, have an impact on how muchpain chronic pain patients then claim to be feeling). All the while, neuroscientists couldbe trying to disentangle how the various components in the limbic system interact witheach other and the rest of the brain so that they can design interventions that will changehow our reward system does its business. Feyerabend’s thousand flowers just mightbloom in peace and harmony.

It could also be the case that, at the end of the day, one or the other disciplines end upsubsuming the rest. It really is too soon to tell. No matter what the outcome, though,neuroscience needs to forge its own theoretical path without leaning so heavily onpsychological categories that have been developed largely uninformed by any neuraldata. Neuroscience needs to stand on its own two feet for a while, independent of andunencumbered by its sister-disciplines. Only the fullness of time will reveal the bestway to understand and treat our human foibles and failings.

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