A common neurobiology for pain and pleasure
Abstract
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.
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Pleasure and pain operate through overlapping neural systems and neurochemical processes that create a common currency of emotion in the brain.
“preclinical and clinical studies suggest that these two opposing phenomena operate via an overlapping set of neural systems and neurochemical processes5 that instantiate a “common currency” of emotion in the brain.6”
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“These aversive processes are believed to interact with appetitive motivational systems, though mechanisms of such interactions are poorly understood (Konorski, 1967; Dickinson and Dearing, 1979; Daw et al., 2002; Fields, 2007; Koob and LeMoal, 2008; Leknes and Tracey, 2008).”
BackgroundLindquist, K. A., Satpute, A. B., Wager, T. D., Weber, J., & Barrett, L. F. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhv001 · Cited by 713 · see citing works
“These findings might suggest that it is not neurons, but neurochemicals, that are valence specific, but research shows that neurochemicals such as opiods and dopamine are general to both pleasure and pain in mammals (Leknes and Tracey 2008).”
BackgroundThe neurobiology of rewards and values in social decision making
Ruff, C. C., & Fehr, E. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3776 · Cited by 716 · see citing works
Mendl, M., Burman, O. H. P., Parker, R. M. A., & Paul, E. S. (2009) · Applied Animal Behaviour Science · doi:10.1016/j.applanim.2009.02.023 · Cited by 763 · see citing works
“This system may thus provide a common currency for valuation of both positive and negative outcomes (Leknes and Tracey, 2008).”
BackgroundMirror neurons: from origin to function
Cook, R., Bird, G., Catmur, C., Press, C., & Heyes, C. (2014) · Behavioral and Brain Sciences · doi:10.1017/s0140525x13000903 · Cited by 632 · see citing works
Descending pain modulation and chronification of pain
Ossipov, M. H., Morimura, K., & Porreca, F. (2014) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0000000000000055 · Cited by 818 · see citing works
“The somatosensory cortices (S1 and S2) and the insula are believed to encode the sensory features of pain, which include quality (stinging, burning or aching), location and duration [37,38 ■ ,39].”
The influence of negative emotions on pain: Behavioral effects and neural mechanisms
Wiech, K., & Tracey, I. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.05.059 · Cited by 614 · see citing works
“A deeper understanding of their neural basis could not only broaden our view on pain, but also open new approaches to treatment of acute and chronic pain states (Leknes and Tracey, 2008).”
Self-citationGetting the pain you expect: mechanisms of placebo, nocebo and reappraisal effects in humans
Tracey, I. (2010) · Nature Medicine · doi:10.1038/nm.2229 · Cited by 553 · see citing works
“Can we harness the powers of reappraisal outside traditional placebo interventions to gain pain relief? Making pain pleasant If cognitive reappraisal involves re-interpreting the importance or meaning of adverse events, such as painful experiences, then is it possible to not only reduce pain but perhaps also reverse c…”
BackgroundSelf-citationMusic and social bonding: “self-other†merging and neurohormonal mechanisms
Tarr, B., Launay, J., & Dunbar, R. I. M. (2014) · Frontiers in Psychology · doi:10.3389/fpsyg.2014.01096 · Cited by 548 · see citing works
“The EOS is central in opioid-mediated reward (Koob, 1992; Olmstead and Franklin, 1997; Comings et al., 1999), social motivation (Chelnokova et al., 2014), and pleasure and pain perception (Janal et al., 1984; Leknes and Tracey, 2008).”
BackgroundTowards a functional neuroanatomy of pleasure and happiness
Kringelbach, M. L., & Berridge, K. C. (2009) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2009.08.006 · Cited by 528 · see citing works
Neuroscience of affect: brain mechanisms of pleasure and displeasure
Berridge, K. C., & Kringelbach, M. L. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.017 · Cited by 532 · see citing works
How neuroimaging studies have challenged us to rethink: Is chronic pain a disease?
Tracey, I., & Bushnell, M. C. (2009) · The Journal of Pain · doi:10.1016/j.jpain.2009.09.001 · Cited by 455 · see citing works
Self-citationReward and motivation in pain and pain relief
Navratilova, E., & Porreca, F. (2014) · Nature Neuroscience · doi:10.1038/nn.3811 · Cited by 481 · see citing works
The human sexual response cycle: Brain imaging evidence linking sex to other pleasures
Georgiadis, J. R., & Kringelbach, M. L. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.05.004 · Cited by 399 · see citing works
“This is interesting in the context of the substantial overlap between the brain regions involved in pleasure and pain (Leknes and Tracey, 2008).”
BackgroundMindfulness training for smoking cessation: Results from a randomized controlled trial
Brewer, J. A., Mallik, S., Babuscio, T. A., Nich, C., Johnson, H. E., Deleone, C. M., Minnix-Cotton, C. A., Byrne, S. A., Kober, H., Weinstein, A. J., et al. (2011) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2011.05.027 · Cited by 383 · see citing works
“…begins in part from the formation of associative memories between smoking and both positive (e.g., after a good meal), and negative (e.g., when “stressed”) affective states (Bevins and Palmatier, 2004; Brown et al., 1996; Kandel and Davies, 1986; Leknes and Tracey, 2008; Piasecki et al., 1997).”
BackgroundYang, S., & Chang, M. C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133130 · Cited by 410 · see citing works
“The prefrontal region and limbic system (ACC, amygdala, VTA, and NAc) are associated with affective aspects of pain and regulate emotional and motivational responses [16,17,25].”
BackgroundNeugebauer, V., Galhardo, V., Maione, S., & Mackey, S. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.12.014 · Cited by 353 · see citing works
“Recent studies have detailed the participation of brain areas outside the somatosensory system in the perception of noxious stimuli (Borsook et al., 2007; Leknes and Tracey, 2008).”
BackgroundLahnakoski, J. M., Glerean, E., Salmi, J., Jääskeläinen, I. P., Sams, M. E., Hari, R., & Nummenmaa, L. (2012) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2012.00233 · Cited by 383 · see citing works
“Finally, the fronto-insular network, comprising the aIns and the medial prefrontal cortex of both hemispheres, reacted to emotions and pain, in line with prior studies (Apkarian et al., 2005; Leknes and Tracey, 2008).”
ResultBeyond the FRN: Broadening the time-course of EEG and ERP components implicated in reward processing
Glazer, J. E., Kelley, N. J., Pornpattananangkul, N., Mittal, V. A., & Nusslock, R. (2018) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2018.02.002 · Cited by 362 · see citing works
“Furthermore, both anticipatory and outcome stages of reward processing can be further divided into several discrete psychological processes associated with their own distinct neurobiological mechanisms (Berridge and Robinson, 2003; Everitt and Robbins, 2005; Kringelbach, 2005; Berridge and Kringelbach, 2008; Leknes an…”
BackgroundCommon brain mechanisms of chronic pain and addiction
Elman, I., & Borsook, D. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.027 · Cited by 303 · see citing works
“The matching law (Herrnstein, 1997) posits that matched rates of the reinforced behavior are moderated by competing prediction errors and their correspondingly matched behavioral outcomes (Fernandez and McDowell, 1995; Fields, 2007; Leknes and Tracey, 2008).”
BackgroundBrewer, J. A., Elwafi, H. M., & Davis, J. H. (2013) · Psychology of Addictive Behaviors · doi:10.1037/a0028490 · Cited by 303 · see citing works
Garland, E. L., Froeliger, B., Zeidan, F., Partin, K., & Howard, M. O. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.08.006 · Cited by 277 · see citing works
Reward and the serotonergic system
Kranz, G. S., Kasper, S. F., & Lanzenberger, R. R. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.01.036 · Cited by 270 · see citing works
Silent disco: dancing in synchrony leads to elevated pain thresholds and social closeness
Tarr, B., Launay, J., & Dunbar, R. I. M. (2016) · Evolution and Human Behavior · doi:10.1016/j.evolhumbehav.2016.02.004 · Cited by 341 · see citing works
“Activation of the EOS is associated with feelings of euphoria (Bodnar, 2008), interpersonal warmth, well-being, and bliss (Depue & Morrone-Strupinsky, 2005), reward (Olmstead & Franklin, 1997), social motivation (Chelnokova et al., 2014), and pleasure and pain perception (Leknes & Tracey, 2008).”
BackgroundThe Distancing-Embracing model of the enjoyment of negative emotions in art reception
Menninghaus, W., Wagner, V., Hanich, J., Wassiliwizky, E., Jacobsen, T., & Koelsch, S. (2017) · Behavioral and Brain Sciences · doi:10.1017/s0140525x17000309 · Cited by 398 · see citing works
Tompkins, D. A., Hobelmann, J. G., & Compton, P. A. (2017) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2016.12.002 · Cited by 251 · see citing works
“Differences between acute and chronic pain A comprehensive review of the pain signaling pathway is beyond the scope of this review, but readers can reference reviews by Clark and Treisman (2004) and Leknes and Tracey (2008) for more information.”
BackgroundPerformance-dependent inhibition of pain by an executive working memory task
Buhle, J., & Wager, T. D. (2010) · Pain · doi:10.1016/j.pain.2009.10.027 · Cited by 249 · see citing works
“However, given the possibility that reward processing may interact with pain [43], future research should confirm that motivated performance of a demanding task can reduce pain regardless of reward context.”
BackgroundGoschke, T., & Bolte, A. (2014) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2014.07.015 · Cited by 298 · see citing works
The anatomy of pain and suffering in the brain and its clinical implications
Ridder, D. D., Adhia, D. B., & Vanneste, S. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.08.013 · Cited by 276 · see citing works
Mesolimbic dopamine signaling in acute and chronic pain
Taylor, A. M. W., Becker, S., Schweinhardt, P., & Cahill, C. M. (2016) · Pain · doi:10.1097/j.pain.0000000000000494 · Cited by 229 · see citing works
“A common suggestion, based on animal studies focusing on pain behavior, some clinical data, and genetic associations, is that dopamine is antinociceptive by D2 receptors.(24,27,33,52,71) Some experimental works in humans supports this notion by showing increased affective pain ratings after dietary dopamine depletion(…”
BackgroundBuilding a neuroscience of pleasure and well-being
Berridge, K. C., & Kringelbach, M. L. (2011) · Psychology of Well-Being: Theory, Research and Practice · doi:10.1186/2211-1522-1-3 · Cited by 229 · see citing works
“…fundamental pleasure is social interaction with conspecifics, which draws on overlapping neural systems and is important even from an evolutionary perspective (Aragona et al. 2006; Britton et al. 2006; Frith and Frith 2010; King-Casas et al. 2005; Kringelbach et al. 2008; Leknes and Tracey 2008).”
BackgroundSomatic and vicarious pain are represented by dissociable multivariate brain patterns
Krishnan, A., Woo, C., Chang, L. J., Ruzic, L. L., Gu, X., López‐Solà, M., Jackson, P. L., Pujol, J., Fan, J., & Wager, T. D. (2016) · eLife · doi:10.7554/elife.15166 · Cited by 233 · see citing works
“It also converges with views of somatic pain as represented by patterns across populations of neurons distributed across macroscopic brain regions ( Coghill et al., 1999 ; Leknes and Tracey, 2008 ; Melzack and Wall, 1967 ).”
BackgroundThomsen, K. R., Whybrow, P. C., & Kringelbach, M. L. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00049 · Cited by 235 · see citing works
“…is instead a complex process containing several psychological components that correspond to distinguishable, and partly dissociable, neurobiological mechanisms, although the terminology may vary (Berridge and Robinson, 2003; Schultz, 2006; Berridge and Kringelbach, 2008; Leknes and Tracey, 2008).”
BackgroundPain and suicidality: Insights from reward and addiction neuroscience
Elman, I., Borsook, D., & Volkow, N. D. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.06.003 · Cited by 220 · see citing works
How Humans Integrate the Prospects of Pain and Reward during Choice
Talmi, D., Dayan, P., Kiebel, S. J., Frith, C., & Dolan, R. J. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2026-09.2009 · Cited by 217 · see citing works
“As anticipated, the main effect of pain activated regions corresponding to a putative pain matrix (Leknes and Tracey, 2008), with clusters in the primary and secondary somatosensory cortex (supplemental table and Fig.”
BackgroundRelief as a reward: hedonic and neural responses to safety from pain
Leknes, S., Lee, M., Berna, C., Andersson, J., & Tracey, I. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017870 · Cited by 207 · see citing works
“Relief from pain fits with the definition of a reward [1,2].”
BackgroundSelf-citationEmotional imagery: Assessing pleasure and arousal in the brain's reward circuitry
Costa, V. D., Lang, P. J., Sabatinelli, D., Versace, F., & Bradley, M. M. (2010) · Human Brain Mapping · doi:10.1002/hbm.20948 · Cited by 202 · see citing works
“On the other hand, based on studies using a wide variety of populations, paradigms, and procedures, there is also evidence that NAc activity increases in response to both pain and pleasure [Leknes and Tracey, 2008].”
BackgroundQuantifying cerebral contributions to pain beyond nociception
Woo, C., Schmidt, L., Krishnan, A., Jepma, M., Roy, M., Lindquist, M. A., Atlas, L. Y., & Wager, T. D. (2017) · Nature Communications · doi:10.1038/ncomms14211 · Cited by 215 · see citing works
Arsalidou, M., Duerden, E. G., & Taylor, M. J. (2012) · Human Brain Mapping · doi:10.1002/hbm.22124 · Cited by 206 · see citing works
“A recent qualitative review indicated that pain and reward pathways were processed similarly by the dorsal and ventral striatum and the globus pallidus [Leknes and Tracey, 2008].”
BackgroundRubı́, B., & Maechler, P. (2010) · Endocrinology · doi:10.1210/en.2010-0745 · Cited by 208 · see citing works
The association between migraine and physical exercise
Amin, F. M., Aristeidou, S., Baraldi, C., Czapińska-Ciepiela, E., Daponte, A., Lenola, D. D., Fenech, C., Kampouris, K., Karagiorgis, G., Braschinsky, M., et al. (2018) · The Journal of Headache and Pain · doi:10.1186/s10194-018-0902-y · Cited by 228 · see citing works
Jhou, T. C., Good, C. H., Rowley, C. S., Xu, S., Wang, H., Burnham, N. W., Hoffman, A. F., Lupica, C. R., & Ikemoto, S. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3634-12.2013 · Cited by 198 · see citing works
“LHb activation is associated with a wide range of negative affective processes (Ullsperger and von Cramon, 2003; Matsumoto and Hikosaka, 2007; Hikosaka et al., 2008; Jhou et al., 2009a; Shumake et al., 2010; Friedman et al., 2011; Li et al., 2011; Stamatakis and Stuber, 2012).”
BackgroundUbuka, T., Lai, H., Kitani, M., Suzuuchi, A., Pham, V., Cadigan, P. A., Wang, A., Chowdhury, V. S., Tsutsui, K., & Bentley, G. E. (2009) · The Journal of Comparative Neurology · doi:10.1002/cne.22191 · Cited by 192 · see citing works
“In contrast, a relatively small number of dopamine neurons in the ventral tegmental area (Leknes and Tracey, 2008) received putative contact from GnIH-ir fibers.”
BackgroundBrain Circuits Encoding Reward from Pain Relief
Navratilova, E., Atcherley, C. W., & Porreca, F. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.09.003 · Cited by 202 · see citing works
“Thus, relief of pain is rewarding and could promote a positive emotional state [37].”
BackgroundPereira, A., & Furlan, F. A. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.07.001 · Cited by 177 · see citing works
“Leknes and Tracey (2008) indicate ''extensive similarities in the anatomical substrates of painful and pleasant sensations (such as) the important role of the opioid and dopamine systems in modulating both pain and pleasure'', pointing to the importance of ''understanding the mutually inhibitory…”
Synchrony as an Adaptive Mechanism for Large‐Scale Human Social Bonding
Launay, J., Tarr, B., & Dunbar, R. (2016) · Ethology · doi:10.1111/eth.12528 · Cited by 202 · see citing works
“The EOS is central in opioid-mediated reward (Koob 1992; Olmstead & Franklin 1997; Comings et al. 1999), social motivation (Chelnokova et al. 2014), and pleasure and pain perception (Janal et al. 1984; Leknes & Tracey 2008), and is associated with feelings of euphoria (Boecker et al. 2008).”
Personality Trait Predictors of Placebo Analgesia and Neurobiological Correlates
Peciña, M., Azhar, H., Love, T., Lu, T., Fredrickson, B. L., Stohler, C. S., & Zubieta, J. K. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.227 · Cited by 187 · see citing works
“Given the overlapping neurobiology of pain, reward and placebo analgesia circuitry (Leknes and Tracey, 2008), it would not be surprising that regions engaged in empathic responses to others would also be involved in placebo responses.”
BackgroundEllingsen, D., Leknes, S., Løseth, G., Wessberg, J., & Olausson, H. (2016) · Frontiers in Psychology · doi:10.3389/fpsyg.2015.01986 · Cited by 195 · see citing works
“First, sensory information enters subjective awareness through the gate of attention (Johansen-Berg et al., 2000) – presuming you are sitting down right now, you might not be aware of the physical pressure of the chair pressing against your skin until this very moment when your attention is…”
BackgroundInfluentialSelf-citationReward, motivation, and emotion of pain and its relief
Porreca, F., & Navratilova, E. (2017) · Pain · doi:10.1097/j.pain.0000000000000798 · Cited by 198 · see citing works
Carruthers, P. (2018) · Philosophy and Phenomenological Research · doi:10.1111/phpr.12395 · Cited by 177 · see citing works
“…involving not just subcortical evaluative regions in the basal ganglia, but also the anterior insula and anterior cingulate, together especially with orbitofrontal and ventromedial prefrontal cortex (Leknes & Tracey, 2008; FitzGerald et al., 2009; Plassmann et al., 2010; Bartra et al., 2013).”
Martucci, K. T., & Mackey, S. (2018) · Anesthesiology · doi:10.1097/aln.0000000000002137 · Cited by 224 · see citing works
Endogenous Opioid Activity in the Anterior Cingulate Cortex Is Required for Relief of Pain
Navratilova, E., Xie, J. Y., Meske, D. S., Qu, C., Morimura, K., Okun, A., Arakawa, N., Ossipov, M. H., Fields, H. L., & Porreca, F. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3862-14.2015 · Cited by 186 · see citing works
“Human and animal studies have identified multiple brain regions, including the insula, prefrontal cortex, anterior cingulate cortex (ACC), amygdala, and dorsal and ventral striatum, involved in processing the affective component of pain (i.e., pain aversiveness; Leknes and Tracey, 2008; Becker et al., 2012; Bushnell e…”
BackgroundAn Empirical Review of the Neural Underpinnings of Receiving and Giving Social Support
Eisenberger, N. I. (2013) · Psychosomatic Medicine · doi:10.1097/psy.0b013e31829de2e7 · Cited by 213 · see citing works
“Rewarding stimuli such as pleasant music or palatable food can reduce pain or threat responding, whereas sustained pain can inhibit the experience of reward from morphine (149,150).”
The importance of context: When relative relief renders pain pleasant
Leknes, S., Berna, C., Lee, M., Snyder, G. D., Biele, G., & Tracey, I. (2012) · Pain · doi:10.1016/j.pain.2012.11.018 · Cited by 187 · see citing works
“Based on previous literature on reward-related and other types of endogenous analgesia [9,14,22,36,47,70], we expected to find recruitment of the PAG in response to the context manipulation.”
BackgroundInfluentialSelf-citationYoshida, W., Seymour, B., Koltzenburg, M., & Dolan, R. J. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4984-12.2013 · Cited by 165 · see citing works
“The first stems from theories of placebo analgesia, and relates to evidence suggesting that induction of reward (putatively dopaminergic) mechanisms, for example during relief prediction, exert an opponent inhibitory influence on pain (de la Fuente-Fernández et al., 2004; Lidstone et al., 2005; Fields, 2006; Scott et…”
BackgroundMethodInfluentialPain, affective symptoms, and cognitive deficits in patients with cerebral dopamine dysfunction
Jarcho, J. M., Mayer, E. A., Jiang, Z. K., Feier, N. A., & London, E. D. (2012) · Pain · doi:10.1016/j.pain.2012.01.002 · Cited by 160 · see citing works
“gions most commonly implicated in pain processing [4] and brain regions that comprise the DA system [86] (see regions highlighted”
BackgroundElwafi, H. M., Witkiewitz, K., Mallik, S., IV, T. A. T., & Brewer, J. A. (2013) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2012.11.015 · Cited by 161 · see citing works
Lowry, P. B., Gaskin, J. E., & Moody, G. D. (2015) · Journal of the Association for Information Systems · doi:10.17705/1jais.00403 · Cited by 143 · see citing works
“Pleasure is a rudimentary state of gratification that results from a sensory stimulus and can have mental and physiological components (Aaker & Lee, 2001; Cabanac, 1979; Cabanac & Ferber, 1987; Leknes & Tracey, 2008).”
BackgroundGavériaux‐Ruff, C., Nozaki, C., Nadal, X., Hever, X. C., Weibel, R., Matifas, A., Reiss, D. J., Filliol, D., Nassar, M. A., Wood, J. N., et al. (2011) · Pain · doi:10.1016/j.pain.2010.12.031 · Cited by 161 · see citing works
“Opioid receptors are also largely distributed in other neural pathways, where they mainly regulate reward and affective states [41,42,46].”
BackgroundRichardson, M., McEwan, K., Maratos, F., & Sheffield, D. (2016) · Evolutionary Psychological Science · doi:10.1007/s40806-016-0065-5 · Cited by 155 · see citing works
“Finally, opioids are well-established in the relief of pain, with research suggesting that both opioid and dopamine systems are important in modulating both pain and pleasure (Leknes and Tracey 2008).”
BackgroundFrom Bad to Worse: Striatal Coding of the Relative Value of Painful Decisions
Brooks, A. M., Pammi, V. S. C., NOUSSAIR, C. N., Capra, C. M., Engelmann, J. B., & Berns, G. S. (2010) · Frontiers in Neuroscience · doi:10.3389/fnins.2010.00176 · Cited by 133 · see citing works
“…signals residing in some of the same regions that we observe, namely in the lateral OFC and genual ACC (O’Doherty et al., 2001; Small et al., 2001; Beyond the striatum’s adaptive coding of value, its more general role in pain processing has been hotly debated (Leknes and Tracey, 2008).”
BackgroundAversive stimulus differentially triggers subsecond dopamine release in reward regions
Budygin, E. A., Park, J., Bass, C. E., Grinevich, V. P., Bonin, K. D., & Wightman, R. M. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2011.10.056 · Cited by 152 · see citing works
“Dopamine signaling in the nucleus accumbens (NAc) is involved in the integration of sensory information and the initiation of the subsequent behavioral responses to diverse stimuli (Leknes and Tracey, 2008).”
BackgroundInfluentialKringelbach, M. L., & Berridge, K. C. (2017) · Emotion Review · doi:10.1177/1754073916684558 · Cited by 187 · see citing works
“In turn, swift progress has been made through the careful study of the objective features of reward behaviour and triangulating toward underlying brain substrates (Berridge & Kringelbach, 2008; Leknes & Tracey, 2008).”
BackgroundNew insights on the subcortical representation of reward
Hikosaka, O., Bromberg-Martin, E. S., Hong, S., & Matsumoto, M. (2008) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2008.07.002 · Cited by 141 · see citing works
“One tempting conclusion drawn from recent experiments is that the opioid system is necessary for hedonic experience, ‘liking’, whereas the dopamine system is important for motivation, ‘wanting’ [46].”
Reason, emotion and decision-making: risk and reward computation with feeling
Quartz, S. R. (2009) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2009.02.003 · Cited by 125 · see citing works
Neural Mechanisms of Reward in Insects
Perry, C. J., & Barron, A. B. (2013) · Annual Review of Entomology · doi:10.1146/annurev-ento-120811-153631 · Cited by 135 · see citing works
Garland, E. L. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13034 · Cited by 137 · see citing works
“A number of hypotheses have been generated from the new perspective emerging from the MORE research program, including the following testable predictions to be pursued in future research: (1) mindfulness strengthens top-down cognitive control; (2) enhancing attentional stability, setshifting capacity, and metacognitiv…”
BackgroundBurkett, J. P., Spiegel, L. L., Inoue, K., Murphy, A. Z., & Young, L. J. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.117 · Cited by 133 · see citing works
“The opiate system has long been known to mediate the rewarding or positively reinforcing properties of unconditioned stimuli such as food, water, sex, and drugs of abuse (Turkish and Cooper, 1983; Agmo and Berenfeld, 1990; Self and Nestler, 1995; Yeomans and Gray, 1996; Fields, 2007; Leknes and Tracey, 2008).”
BackgroundKong, F., Hu, S., Wang, X., Song, Y., & Liu, J. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.11.033 · Cited by 136 · see citing works
“, 2011) and encoding reward values of pain or pleasure (Leknes and Tracey, 2008; Kringelbach, 2005; O'Doherty et al., 2001).”
Evaluation of reward from pain relief
Navratilova, E., Xie, J. Y., King, T. E., & Porreca, F. (2013) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12095 · Cited by 147 · see citing works
Opioid Release after High-Intensity Interval Training in Healthy Human Subjects
Saanijoki, T., Tuominen, L. J., Tuulari, J. J., Nummenmaa, L., Arponen, E., Kalliokoski, K. K., & Hirvonen, J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.148 · Cited by 136 · see citing works
Li, Z., Liu, M., Lan, L., Zeng, F., Makris, N., Liang, Y., Guo, T., Wu, F., Gao, Y., Dong, M., et al. (2016) · Scientific Reports · doi:10.1038/srep20298 · Cited by 127 · see citing works
“We also observed that the pre-and post-treatment rs-fc change between the PAG and the reward system (including nucleus accumbens/ventral striatum, putamen and left caudate/dorsal striatum) 49 is significantly associated with migraine headache intensity relief.”
BackgroundAnimal affect and decision-making
Mendl, M., & Paul, E. S. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.01.025 · Cited by 161 · see citing works
“…are anticipating), they experience short-term negative affect (e.g. ‘anxiety’ or ‘fear’ and ‘disappointment’ respectively) (Camille et al., 2004; Carver, 2001; Leknes and Tracey, 2008; Mellers et al., 1999; Mellers, 2000; Seymour et al., 2005; Watson and Tellegen, 1985; Zeelenberg et al., 2000).”
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“These observations have been extensively replicated [14,15,16,17,18] and synopsized [19,20,21].”
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“With regards to the right ACC, the migraine patients showed increased RSFC with the bilateral OFC (Figure3. b).”
BackgroundInfluentialBrain’s Reward Circuits Mediate Itch Relief. A Functional MRI Study of Active Scratching
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“In this respect, our results slightly differ from studies of pain, which suggest that the same circuits process reward and analgesia [14,15].”
ResultPain induces adaptations in ventral tegmental area dopamine neurons to drive anhedonia-like behavior
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“The endogenous μ-opioid receptor (MOR) system modulates both pain and pleasure (Leknes and Tracey, 2008), as well as behaviors related both to food (Berridge, 1996) and to social rewards such as sex (Mahler and Berridge, 2012) or affiliation (Lutz and Kieffer, 2013).”
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“” Pleasure and pain show similarities both in terms of neurochemistry and systems neurophysiology (10, 28).”
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Slow brushing reduces heat pain in humans
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“It has been demonstrated that rewarding stimuli such as food and pleasurable music decrease pain sensitivity (Leknes and Tracey, 2008), whereas pain can impair reward processing, which can lead to an anhedonic state (Marbach and Lund, 1981; Nicholson and Verma, 2004; Elman et al., 2013).”
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Nonsuicidal Self-Injury, Pain, and Self-Criticism
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- Authors
- Leknes, S., & Tracey, I.
- Affiliations
- John Radcliffe Hospital (GB)
- Corresponding author
- Tracey, Irene
- Venue
- Nature Reviews Neuroscience
- Published
- 2008-04
- Volume
- 9
- Issue
- 4
- Pages
- 314-320
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2050134288
- Semantic Scholar
- 5c7a6d152be4a14216e5ff7dcd87fefc35df55fe
- Cited by
- 784
- References
- 0
- Citations by year
- 2026: 43 · 2025: 33 · 2024: 48 · 2023: 31 · 2022: 61 · 2021: 42 · 2020: 47 · 2019: 49 · 2018: 46 · 2017: 52 · 2016: 52 · 2015: 53 · 2014: 45 · 2013: 59 · 2012: 39
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Keywords
- pain, pleasure, reward, opioid system, dopaminergic system, molecular imaging, well-being, suffering
- MeSH terms
- Animals, Emotions, Humans, Neurobiology, Pain, Pleasure-Pain Principle
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