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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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“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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Items 201–300 of 669
Striatal hypofunction as a neural correlate of mood alterations in chronic pain patients
Kim, M., Mawla, I., Albrecht, D., Admon, R., Torrado-Carvajal, Á., Bergan, C., Protsenko, E., Kumar, P., Edwards, R. R., Saha, A., et al. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116656 · Cited by 46
“A wealth of animal and human research indicates that pain and anhedonia share common neuroanatomical substrates involving the reward systems (de Heer et al., 2014; Garland et al., 2019; Leknes and Tracey, 2008), such as reduced activity in the striatum and anomalies in reward processing.”
BackgroundAltered prefrontal correlates of monetary anticipation and outcome in chronic pain
Martucci, K. T., Borg, N., MacNiven, K. H., Knutson, B. D., & Mackey, S. (2018) · Pain · doi:10.1097/j.pain.0000000000001232 · Cited by 46
Ly, H. G., Ceccarini, J., Weltens, N., Bormans, G., van Laere, K., Tack, J., & van Oudenhove, L. (2015) · Psychotherapy and Psychosomatics · doi:10.1159/000375454 · Cited by 44
The Experience of Pleasure: A Perspective Between Neuroscience and Psychoanalysis
Moccia, L., Mazza, M., Nicola, M. D., & Janiri, L. (2018) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2018.00359 · Cited by 48
“A determining factor is subjective utility or individual motivation, termed meaning, which has been shown to be conditioned by sensorial, homoeostatic, and cultural characteristics (Leknes and Tracey, 2008).”
BackgroundInfluentialAlbrecht, P. J., & Rice, F. L. (2016) · Reviews on Environmental Health · doi:10.1515/reveh-2015-0040 · Cited by 46
Pirro, S. D., Galati, G., Pizzamiglio, L., & Badiani, A. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0019-18.2018 · Cited by 48
“…is interconnected with the striatum (Hoshi et al., 2005), which is implicated in processing not only rewarding but also aversive stimuli (Ungless et al., 2004; Schultz, 2007; Leknes and Tracey, 2008), particularly the dorsal striatum (Delgado et al., 2003; Seymour et al., 2007; Gorka et al., 2017).”
BackgroundAcupuncture for Cancer-Induced Bone Pain?
Paley, C. A., Bennett, M., & Johnson, M. I. (2011) · Evidence-Based Complementary and Alternative Medicine · doi:10.1093/ecam/neq020 · Cited by 42
“The way acupuncture affects the emotional component of CIBP has emerged as a result of brain imaging studies, which show that sensory input may be modulated by the emotional reaction and cognitive aspects of pain and vice versa [55–57].”
BackgroundHedonic Hotspots Regulate Cingulate-driven Adaptation to Cognitive Demands
van Steenbergen, H., Band, G. P. H., Hommel, B., Rombouts, S. A. R. B., & Nieuwenhuis, S. (2014) · Cerebral Cortex · doi:10.1093/cercor/bht416 · Cited by 45
Nishizawa, D., Fukuda, K., Kasai, S., Ogai, Y., Hasegawa, J., Sato, N., Yamada, H., Tanioka, F., Sugimura, H., Hayashida, M., et al. (2014) · Journal of Pharmacological Sciences · doi:10.1254/jphs.14189fp · Cited by 45
Borg, C., de Jong, P. J., & Georgiadis, J. R. (2012) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nss117 · Cited by 47
“We have already seen that the amygdala may be capable of both appetitive and aversive processing (Leknes and Tracey, 2008), and that this relates to associative learning (Paton et al.”
BackgroundMatsudaira, K., Kawaguchi, M., Isomura, T., Inuzuka, K., Tadashi, K. O. G. A., Miyoshi, K., & KONISHI, H. (2015) · Industrial Health · doi:10.2486/indhealth.2014-0260 · Cited by 42
Mohseni, H., Smith, P. P., Parsons, C. E., Young, K. S., Hyam, J. A., Stein, A. L., Stein, J. F., Green, A. L., Aziz, T. Z., & Kringelbach, M. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037993 · Cited by 38
“Our findings of PAG and the pre-SMA involvement are also consistent with fMRI studies of acute pain in healthy adults [19].”
ResultNiklasson, A., Finan, P., Smith, M. T., Forsberg, A., Dietz, N., Kander, T., Werner, M. U., Irwin, M. R., Kosek, E., & Bjurström, M. F. (2024) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2024.102014 · Cited by 42
Wang, C.-T., Mao, C., Zhang, X., Zhang, C.-Y., Lv, D.-J., Yang, Y., Xia, K.-L., Liu, J., Wang, F., Hu, L., et al. (2017) · Molecular Pain · doi:10.1177/1744806917691525 · Cited by 46
“A relationship between the dopaminergic system and pain in both healthy subjects and patients suffering from some pain conditions has been reported.(8,9) Moreover, an effect of L-3,4-dihydroxyphenylalanine on pain threshold has also been demonstrated in patients with PD-related pain.”
BackgroundMaladaptive behavior and affect regulation: A functionalist perspective.
Swerdlow, B. A., Pearlstein, J. G., Sandel, D. B., Mauss, I. B., & Johnson, S. L. (2020) · Emotion · doi:10.1037/emo0000660 · Cited by 38
“…affect: an individual who is perpetually in extreme distress is further from allostasis and capable of experiencing much greater relief than one who is only briefly or mildly distressed, such that the value of the relief is greater for the first individual than the second (Leknes & Tracey, 2008).”
BackgroundPhysical Pain as Pleasure: A Theoretical Perspective
Dunkley, C. R., Henshaw, C. D., Henshaw, S. K., & Brotto, L. A. (2019) · The Journal of Sex Research · doi:10.1080/00224499.2019.1605328 · Cited by 47
“Sensory stimuli and context also play a central role in facilitating sexual arousal (Basson, 2008), which has been found to mitigate pain (Leknes & Tracey, 2008).”
BackgroundResultInfluentialCortical Responses to Alien Odors in Newborns: An fNIRS Study
Frie, J., Bartocci, M., Lagercrantz, H., & Kuhn, P. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx194 · Cited by 44
“Some evidence suggests that the “analgesic” effect of glucose could be due to a distraction or a compensatory pleasure (Leknes and Tracey 2008; Berridge and Kringelbach 2015).”
BackgroundA Novel Role for the Periaqueductal Gray in Consummatory Behavior
Tryon, V. L., & Mizumori, S. J. Y. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00178 · Cited by 34
“Indeed, it has been documented that expectancy of a food reward can activate endogenous opioid-mediated analgesia which is thought to be mediated by the PAG (Dum and Herz, 1984; Fields, 2004) and it is hypothesized that reward expectation elicits an analgesic response to allow an animal to ignore noxious stimuli and a…”
BackgroundMoriya, S., Yamashita, A., Kawashima, S., Nishi, R., Yamanaka, A., & Kuwaki, T. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.06.027 · Cited by 41
“Although the consequences resulting from the activation of VTA DA neurons have not been studied here, there is a common suggestion that DA is acting on D2 receptors in an anti-nociceptive way (Leknes and Tracey, 2008; Jarcho et al., 2012).”
Functionality versus dimensionality in psychological taxonomies, and a puzzle of emotional valence
Trofimova, I. N. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2017.0167 · Cited by 34
Opioid Modulation of Value-Based Decision-Making in Healthy Humans
Eikemo, M., Biele, G., Willoch, F., Thomsen, L., & Leknes, S. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.58 · Cited by 39
“In humans, the MOR system is best known as a moderator of pain and pleasure (eg, Leknes and Tracey, 2008).”
BackgroundSelf-citationHedonic and motivational responses to food reward are unchanged in rats with neuropathic pain
Okun, A., McKinzie, D. L., Witkin, J. M., Remeniuk, B., Husein, O. F., Gleason, S. D., Oyarzo, J. N., Navratilova, E., McElroy, B., Cowen, S. L., et al. (2016) · Pain · doi:10.1097/j.pain.0000000000000695 · Cited by 37
“As predicted by the motivation–decision model,(16) a decreased pain response to a nociceptive stimulus is observed in the setting of available rewards.(22) Conversely, acute painful stimuli could diminish the value of rewards.”
BackgroundPorta, C. L., Lara-Mayorga, I. M., Negrete, R., & Maldonado, R. J. (2016) · European Journal of Pain · doi:10.1002/ejp.868 · Cited by 42
“Large overlaps exist in the anatomical and neurochemical substrates of pain and reward, which could explain the mutual influence between these processes (Leknes and Tracey, 2008).”
BackgroundPain, from perception to action: A computational perspective
Chen, Z. S., & Wang, J. (2022) · iScience · doi:10.1016/j.isci.2022.105707 · Cited by 38
“7,62 In the midbrain mesolimbic dopamine system, dopaminergic (DA) signaling was found in the presence of not only appetitive stimuli (‘‘reward’’) but also aversive stimuli (‘‘pain’’), 63–66 where salience-coding DA signaling is similar for pain and reward.”
BackgroundDopaminergic modulation of pain signals in the medial prefrontal cortex: Challenges and perspectives
Huang, S., Borgland, S. L., & Zamponi, G. W. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.11.043 · Cited by 38
DosSantos, M. F. H., Oliveira, A. T., Ferreira, N. R., Carvalho, A. C. P., & Rosado-de-Castro, P. H. (2018) · Pain Research and Management · doi:10.1155/2018/2368386 · Cited by 44
“In the CNS, dopamine participates in diverse functions such as motor control, reward system as well as pain transmission and modulation [75, 76].”
BackgroundWu, L., Li, X., Chen, T., Ren, M., & Zhuo, M. (2009) · Molecular Brain · doi:10.1186/1756-6606-2-32 · Cited by 36
“Studies from both animals and humans consistently demonstrate that the ACC plays a critical role in emotional and attentive responses to internal and external stimulation, such as pain, fear, anxiety, sexual arousal, learning and memory [1-9].”
BackgroundThe affective grounds of the mind. The Affective Pertinentization (APER) model
Salvatore, S., Palmieri, A., Picione, R. D. L., Bochicchio, V., Reho, M., Serio, M. R., & Salvatore, G. (2024) · Physics of Life Reviews · doi:10.1016/j.plrev.2024.07.008 · Cited by 35
Negrete, R., García‐Gutiérrez, M. S., Manzanares, J., & Maldonado, R. J. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.08.026 · Cited by 36
“…often experience emotional symptoms, such as anhedonia (Apkarian et al., 2004; Bushnell et al., 2013; Leknes and Tracey, 2008) or anxiety (Leknes and Tracey, 2008; Maldonado and Valverde, 2003) and memory cologia, Universitat Pompeu ), C/ Dr. Aiguader, 88, 08003, ldonado). dysfunctions…”
InfluentialBecker, S., Čeko, M., Louis-Foster, M., Elfassy, N. M., Leyton, M., Shir, Y., & Schweinhardt, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080766 · Cited by 33
Porges, E. C., & Decety, J. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00447 · Cited by 34
“During the past decade, a number of functional neuroimaging studies have investigated the neural response while observing other individuals being hurt (Morrison et al., 2004; Jackson et al., 2005a; Cheng et al., 2007; Gu and Han, 2007; Lamm et al., 2007a,b; Moriguchi et al., 2007; Zaki et al.,…”
BackgroundDiminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain
Jarcho, J. M., Feier, N. A., Bert, A., Labus, J. S., Lee, M., Stains, J., Ebrat, B., Groman, S. M., Tillisch, K., Brody, A. L., et al. (2013) · Pain · doi:10.1016/j.pain.2013.02.026 · Cited by 35
“Unlike those with injury-related pain, IBD patients also had diminished NK-1R availability in striatum, a region that is increasingly associated with pain processing [40].”
BackgroundAltarifi, A. A., Rice, K. C., & Negus, S. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.219873 · Cited by 34
Getting in touch: A neural model of comforting touch
Shamay‐Tsoory, S., & Eisenberger, N. I. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.08.030 · Cited by 39
“Notably, it has been suggested that pleasure and pain share similar mechanisms, pointing to potentially reciprocal inhibitory mechanisms which may take place in brain areas in which adjacent subregions encode aversive and appetitive processing (Leknes and Tracey, 2008).”
BackgroundPositivity versus negativity is a matter of timing
Menninghaus, W., Wagner, V., Hanich, J., Wassiliwizky, E., Jacobsen, T., & Koelsch, S. (2017) · Behavioral and Brain Sciences · doi:10.1017/s0140525x17001820 · Cited by 33
Brain substrates of reward processing and the μ-opioid receptor: a pathway into pain?
Nees, F., Becker, S., Millenet, S., Banaschewski, T., Poustka, L., Bokde, A. L. W., Bromberg, U., Büchel, C., Conrod, P., Desrivières, S., et al. (2017) · Pain · doi:10.1097/j.pain.0000000000000720 · Cited by 35
Triple-aspect monism: A conceptual framework for the science of human consciousness
Pereira, A. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9781139207065.011 · Cited by 37
Silva, J. T. D., Zhang, Y., Asgar, J., Ro, J. Y., & Seminowicz, D. A. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.04.055 · Cited by 33
“In addition, stress and anxiety circuitry shows connections between ACC and insula, as well as projections to NAc that receives glutamatergic outputs from the amygdala and dopaminergic terminals from the VTA [64,65].”
Fu, R., Zuo, W., Gregor, D. M., Li, J., Grech, D., & Ye, J.-H. (2016) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12974 · Cited by 33
“All of these evidences indicate that strong aversive stimuli can inhibit drug-seeking behavior (Fields, 2007; Jhou et al., 2013; Leknes and Tracey, 2008).”
BackgroundPain Reduces Sexual Motivation in Female But Not Male Mice
Farmer, M., Leja, A., Foxen-Craft, E., Chan, L., Macintyre, L., Niaki, T., Chen, M., Mapplebeck, J. C. S., Tabry, V., Topham, L., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.5337-13.2014 · Cited by 32
“Pain, which often accompanies physical injury and disease, modulates diverse motivational states (Leknes and Tracey, 2008), and thus pain may diminish the rewarding properties of sexual activity in a sex-specific manner consistent with sexual selection strategies (Trivers, 1972).”
BackgroundPerinatal effect of methamphetamine on nociception in adult Wistar rats
Yamamotová, A., Hrubá, L., Schutová, B., Rokyta, R., & Šlamberová, R. (2010) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2010.08.004 · Cited by 27
“Therefore, brain reward circuitry is another key target for pharmacological treatment of pain (Borsook et al., 2007; Leknes and Tracey, 2008).”
BackgroundGustatory pleasure and pain. The offset of acute physical pain enhances responsiveness to taste
Bastian, B. B., Jetten, J., & Hornsey, M. J. (2013) · Appetite · doi:10.1016/j.appet.2013.10.011 · Cited by 39
Pain-related cortico-limbic plasticity and opioid signaling
Neugebauer, V., Presto, P., Yakhnitsa, V., Antenucci, N., Mendoza, B., & Ji, G. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109510 · Cited by 38
The perception of affective touch in Parkinson's disease and its relation to small fibre neuropathy
Kass‐Iliyya, L., Leung, M., Marshall, A. G., Trotter, P. D., Kobylecki, C., Walker, S. C., Gosal, D. Y., Jeziorska, M., Malik, R. A., McGlone, F. P., et al. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13481 · Cited by 30
“…brain regions responsible for processing pain and reward (mesolimbic dopamine pathway, prefrontal medial cortex, insular cortex) as well as the common neurochemistry between the two systems (opioid and dopamine; Schultz, 2007; Smith & Berridge, 2007; Wager et al., 2007; Leknes & Tracey, 2008).”
Hedonic Tone and the Heterogeneity of Pleasure
Labukt, I. R. (2012) · Utilitas · doi:10.1017/s0953820812000052 · Cited by 52
Strand, N. H., D'Souza, R. S., Gomez, D. A., Whitney, M. A., Attanti, S., Anderson, M. A., Moeschler, S. M., Chadwick, A. L., & Maloney, J. A. (2024) · Maturitas · doi:10.1016/j.maturitas.2024.108135 · Cited by 30
Cummings, L. R., Mattfeld, A. T., Pettit, J. W., & McMakin, D. L. (2021) · Clinical Psychological Science · doi:10.1177/2167702621989323 · Cited by 33
“…with increased activation in neural networks implicated in reinforcement learning (Baliki et al., 2010; DosSantos et al., 2017; Gerber et al., 2014; Leknes & Tracey, 2008; Mayer et al., 2018; Navratilova et al., 2012, 2015; Nelson & Panksepp, 1998; Oleson et al., 2012; Panksepp et al., 1985;…”
Büchel, C. (2023) · eLife · doi:10.7554/elife.81795 · Cited by 37
“The organism decides (subconsciously or consciously) whether it is advantageous to attend to pain, or a competing motivational state (Leknes and Tracey, 2008).”
BackgroundMusical Enjoyment and Reward: From Hedonic Pleasure to Eudaimonic Listening
Reybrouck, M., & Eerola, T. (2022) · Behavioral Sciences · doi:10.3390/bs12050154 · Cited by 40
Acute orofacial pain leads to prolonged changes in behavioral and affective pain components
Araya, E. I., Baggio, D. F., Koren, L. D. O., Andreatini, R., Schwarting, R. K. W., Zamponi, G. W., & Chichorro, J. G. (2020) · Pain · doi:10.1097/j.pain.0000000000001970 · Cited by 30
“Thus, rewards, including rewarding analgesic drugs, activate mesolimbic neurons and cause the release of dopamine in the NAc, which receives projections from dopaminergic neurons in the ventral tegmental area.(37) Accordingly, data from this study demonstrated that morphine induced CPP on day 3 after the induction of…”
BackgroundNew and emerging therapeutic agents for the treatment of fibromyalgia: an update
Recla, J. M. (2010) · Journal of Pain Research · doi:10.2147/jpr.s6792 · Cited by 29
“…and emotional evaluation which are cognitive functions known to be involved in the experience of chronic pain, including that associated with FM. 49–51 Taken together, these observations suggest a physiologic mechanism of action for milnacipran in FM patients involving both pain inhibitory…”
Watanabe, M., & Narita, M. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1756-9_17 · Cited by 34
GDNF/RET signaling in dopamine neurons in vivo
Conway, J. A., Ince, S., Black, S., & Kramer, E. R. (2020) · Cell and Tissue Research · doi:10.1007/s00441-020-03268-9 · Cited by 33
Hub disruption in patients with chronic neck pain: a graph analytical approach
Pauw, R. D., Aerts, H., Šiugždaitė, R., Meeus, M., Coppieters, I., Caeyenberghs, K., & Cagnie, B. J. (2019) · Pain · doi:10.1097/j.pain.0000000000001762 · Cited by 30
“They are furthermore particularly well situated to mediate interactions between pain and pleasure.(13,53)”
BackgroundChaillou, A.-C., Giersch, A., Hoonakker, M., Capa, R. L., & Bonnefond, A. (2017) · Biological Psychology · doi:10.1016/j.biopsycho.2017.03.009 · Cited by 33
“…(Berridge & Robinson, 2003), based on distinct neurobiological mechanisms (Berridge & Kringelbach, 2008; Berridge, Robinson, & Aldridge, 2009; Leknes & Tracey, 2008; Schultz, 2006), whose respective activation is thought to have different effects on cognitive control (Notebaert & Braem, 2015).”
BackgroundFrom sensing to emergent adaptations: Modelling the proximate architecture for decision-making
Eliassen, S., Andersen, B. S., Jørgensen, C., & Giske, J. (2015) · Ecological Modelling · doi:10.1016/j.ecolmodel.2015.09.001 · Cited by 26
Kim, T., Kang, H., & Jeong, G.-W. (2013) · The Journal of Sexual Medicine · doi:10.1111/jsm.12057 · Cited by 27
Almela, P., Zaragoza, J. N., García-Carmona, J. A., Mora, L., Hidalgo, J. M., Milanés, M. V., & Laorden, M. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047089 · Cited by 28
“DA signalling in the NAc is involved in the integration of sensory information and the initiation of the subsequent behavioural responses to diverse stimuli [41].”
BackgroundTimmerman, H., van Boekel, R. L. M., van de Linde, L. S., Bronkhorst, E. M., Vissers, K. C. P., van der Wal, S. E. I., & Steegers, M. A. H. (2023) · PLoS ONE · doi:10.1371/journal.pone.0280036 · Cited by 26
“It has been suggested that the release of endogenous opioids within the brain and spinal cord, in response to pleasurable music, is responsible for its beneficial effects [29,30].”
BackgroundBliss-Moreau, E., & Rudebeck, P. (2020) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.06.024 · Cited by 27
A Theoretical Computer Science Perspective on Consciousness
Blum, M., & Blum, L. (2021) · Journal of Artificial Intelligence and Consciousness · doi:10.1142/s2705078521500028 · Cited by 32
“…this pain to all pains and consequently “suckling has been shown to relieve pain in infants, even when the pain has nothing to do with hunger per se” (Leknes & Tracey, 2008).52 On the other hand, since a child does not learn to avoid pleasure, she will not seek pain to counter-balance pleasure.”
BackgroundWhy Do Birds Flock? A Role for Opioids in the Reinforcement of Gregarious Social Interactions
Riters, L. V., Kelm‐Nelson, C. A., & Spool, J. A. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00421 · Cited by 29
Li, A.-L., Sibi, J. E., Yang, X., Chiao, J. ‐., & Peng, Y. B. (2016) · Experimental Brain Research · doi:10.1007/s00221-016-4558-z · Cited by 31
“Obviously, the rewarding or pleasure system shares significantly large neural networks with the pain processing system (Leknes and Tracey 2008; Namburi et al. 2015; Whalley 2015).”
κ-opioid receptor as a key mediator in the regulation of appetitive 50-kHz ultrasonic vocalizations
Hamed, A., Szyndler, J., Taracha, E., Turzyńska, D., Sobolewska, A., Lehner, M., Krząścik, P., & Daszczuk, P. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3824-7 · Cited by 28
“It is interesting that also aversive stimuli may increase dopamine levels in the NAcc and in the VTA (Abercrombie et al. 1989; Leknes and Tracey 2008; Brischoux et al. 2009).”
BackgroundInoue, K., Burkett, J. P., & Young, L. J. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.03.035 · Cited by 33
“The μ-opioid receptor (MOR) seems to be principally involved in modulating the hedonic properties of many addictive drugs as well as endogenous reward and pain (van Ree et al., 1999, Leknes and Tracey, 2008, Loyd et al., 2008).”
BackgroundAntioch, I., Furuta, T., Uchikawa, R., Okumura, M., Otogoto, J.-I., Kondo, E., Sogawa, N., Ciobica, A. S., & Tomida, M. (2020) · Journal of Pain Research · doi:10.2147/jpr.s276274 · Cited by 36
A mu-Opioid Feedback Model of Human Social Behavior.
Meier, I., van Honk, J., Bos, P., & Terburg, D. (2020) · Neuroscience and Biobehavioral Reviews · doi:10.31234/osf.io/mhjyw · Cited by 25
“Indeed, the effects of pain on pleasure and vice versa (Leknes and Tracey, 2008) as well as the effect of stress and cortisol on reward”
BackgroundInfluentialSlavich, G. M., Shields, G. S., Deal, B., Gregory, A., & Toussaint, L. L. (2019) · Annals of Behavioral Medicine · doi:10.1093/abm/kaz015 · Cited by 30
Phasic and Tonic Pain Differentially Impact the Interruptive Function of Pain
Sinke, C., Schmidt, K., Forkmann, K., & Bingel, U. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118363 · Cited by 26
“Pain naturally induces avoidance behavior to reduce current harm or prevent the individual from further injury and therefore ensures our survival [1].”
BackgroundPleasure-Related Analgesia Activates Opioid-Insensitive Circuits
Kut, E., Candia, V., von Overbeck, J., Pok, J., Fink, D., & Folkers, G. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3736-10.2011 · Cited by 30
“Even if the precise role of dopamine in pain and reward is far from unequivocal (Leknes and Tracey, 2008), and its function varies at different time courses (Schultz, 2007), some recent evidence suggests a possible opioid-independent dopaminergic me- 40 50 60 70 80 90 100 Block 1 Block 2 V A S p a…”
BackgroundInfluentialLöffler, A., Kleindienst, N., Neukel, C., Bekrater‐Bodmann, R., & Flor, H. (2022) · Borderline Personality Disorder and Emotion Dysregulation · doi:10.1186/s40479-021-00176-4 · Cited by 29
“There is a common neurobiology of pain and pleasure [23] and evidence for cognitive top-down”
BackgroundKim, D. J., Jassar, H., Lim, M., Nascimento, T. D., & DaSilva, A. F. M. (2021) · Journal of Pain Research · doi:10.2147/jpr.s296540 · Cited by 31
Frimerman, L., Verner, M., Sirois, A., Scott, K., Bruneau, A., Pérez, J., Shir, Y., & Martel, M. O. (2021) · Pain · doi:10.1097/j.pain.0000000000002220 · Cited by 26
Wilkinson, D. J. C., Savulescu, J., & Slater, R. (2012) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpediatrics.2012.352 · Cited by 25
“Pleasant odors, images, music, and food have all been reported to decrease pain.(53) The analgesic property of sucrose appears to be related to sweet preferences in children—in one study, children who preferred more sugary solutions tolerated higher levels of a painful stimulus when given sucrose, supporting the pleas…”
BackgroundIlango, A., Wetzel, W., Scheich, H., & Ohl, F. W. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.01.010 · Cited by 22
Sexual attraction enhances glutamate transmission in mammalian anterior cingulate cortex
Wu, L., Kim, S. S., Li, X., Zhang, F., & Zhuo, M. (2009) · Molecular Brain · doi:10.1186/1756-6606-2-9 · Cited by 23
“Discussion In the present study, we focused on sexual attraction and the ACC, a region known to be associated in pain and pleasure [11].”
BackgroundFusaro, M., Bufacchi, R. J., Nicolardi, V., & Provenzano, L. (2022) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2022.956510 · Cited by 30
“It has been demonstrated that pleasant touch can successfully reduce experimentally induced pain (Leknes and Tracey, 2008).”
BackgroundLunde, S. J., Vuust, P., Garza‐Villarreal, E. A., Kirsch, I., Møller, A., & Vase, L. (2022) · Frontiers in Pain Research · doi:10.3389/fpain.2022.734999 · Cited by 24
“The opioid and dopamine systems contribute to a shared neurobiological foundation for pleasure and pain modulation (26), making them eligible candidates for mediating the analgesic effect of music.”
BackgroundKim, H., Nanavaty, N., Ahmed, H., Mathur, V. A., & Anderson, B. A. (2021) · Journal of Cognitive Neuroscience · doi:10.1162/jocn_a_01769 · Cited by 30
“This conclusion is in accordance with growing evidence for valence-independent representations of appetitive and aversive information in the brain (Lindquist, Satpute, Wager, Weber, & Barrett, 2016; Leknes & Tracey, 2008; Seeley et al., 2007).”
ResultPrognostic psychosocial factors for disabling low back pain in Japanese hospital workers
Yoshimoto, T., Oka, H., Katsuhira, J., Fujii, T., Masuda, K., Tanaka, S., & Matsudaira, K. (2017) · PLoS ONE · doi:10.1371/journal.pone.0177908 · Cited by 25
Migraine and Reward System—Or Is It Aversive?
Cahill, C. M., Cook, C. P., & Pickens, S. R. (2014) · Current Pain and Headache Reports · doi:10.1007/s11916-014-0410-y · Cited by 25
Neuroimaging as a Tool for Pain Diagnosis and Analgesic Development
Wartolowska, K. A., & Tracey, I. (2009) · Neurotherapeutics · doi:10.1016/j.nurt.2009.08.003 · Cited by 27
“Understanding the neural basis of pleasure and relief provides alternative strategies and potential targets for intervention aimed at taking the pain away.(70)”
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Neuromodulatory Signaling in Chronic Pain Patients: A Narrative Review
Varrassi, G., Leoni, M. L. G., Farì, G., Al-Alwany, A. A., Sharie, S. A., & Fornasari, D. (2025) · Cells · doi:10.3390/cells14171320 · Cited by 29
“…dopamine system, encompassing projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc), is traditionally associated with reward processing and motivation, yet is now increasingly recognized as a central node in the regulation of pain affect and relief expectancy [25–27].”
Liu, C.-Y., & Yin, B. (2024) · Computers in Human Behavior · doi:10.1016/j.chb.2024.108406 · Cited by 28
Positive valence systems in youth anxiety development: A scoping review
Sequeira, S. L., Forbes, E. E., Hanson, J. L., & Silk, J. S. (2022) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2022.102588 · Cited by 23
Revisiting positive affect and reward influences on cognitive control
Chiew, K. S. (2020) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2020.11.010 · Cited by 26
Increased Experimental Pain Sensitivity in Chronic Pain Patients Who Developed Opioid Use Disorder
Compton, P. A., Wasser, T., & Cheatle, M. D. (2020) · Clinical Journal of Pain · doi:10.1097/ajp.0000000000000855 · Cited by 26
Fu, B., Wen, S., Wang, B., Wang, K., Zhang, J., Weng, X., & Liu, S.-J. (2018) · Journal of Pain Research · doi:10.2147/jpr.s170167 · Cited by 31
“32 The present study used a single injection of GBP to inhibit neuropathic pain, followed by chronic injection for 14 days.”
Different mean thickness implicates involvement of the cortex in migraine
Yu, Z., Peng, J., Lv, Y.-B., Zhao, M., Xie, B., Liang, M., Li, H., & Zhou, Z. (2016) · Medicine · doi:10.1097/md.0000000000004824 · Cited by 23
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Fernando, A. B. P., Urcelay, G. P., Mar, A. C., Dickinson, A., & Robbins, T. W. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4146-13.2014 · Cited by 26
“Therefore, the experience of pain can be influenced not only by its sensory properties, but also by the motivational state of the subject (Leknes and Tracey, 2008).”
BackgroundKirkcaldie, M. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-369497-3.10004-4 · Cited by 45
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Impaired generalization of reward but not loss in obsessive-compulsive disorder
Rouhani, N., Wimmer, G. E., Schneier, F. R., Fyer, A. J., Shohamy, D., & Simpson, H. B. (2019) · Depression and Anxiety · doi:10.1002/da.22857 · Cited by 21
Neuroimmune interactions in painful TMD: Mechanisms and treatment implications
Yi, Y., Zhou, X., Xiong, X., & Wang, J. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0621-731rr · Cited by 21
Contingent Tunes of Neurochemical Ensembles in the Norm and Pathology: Can We See the Patterns?
Trofimova, I. N. (2021) · Neuropsychobiology · doi:10.1159/000513688 · Cited by 21
“Hypothetically, MOR action can be summarized as inducing a feeling of lower needs, to reach a needs/capacities balance, as a combination of the following: • Enhancing coping with pain (analgesic effects), both physical and emotional [93, 158].”
BackgroundMusic‐Related Interventions in the Exercise Domain
Karageorghis, C. I. (2020) · Wiley eBooks · doi:10.1002/9781119568124.ch45 · Cited by 71
A general theoretical framework for the design of artificial emotion systems in Autonomous Agents
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Naltrexone alters responses to social and physical warmth: implications for social bonding
Inagaki, T. K., Hazlett, L. I., & Andreescu, C. (2019) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsz026 · Cited by 25
“One candidate system that has received increasing attention in recent years is the endogenous opioid system, best known for its role in pain relief and pleasure (Leknes and Tracey, 2008).”
Background
Metadata
- 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 (medical) › 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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