Dissociable roles of cerebral μ-opioid and type 2 dopamine receptors in vicarious pain: A combined PET-fMRI study

Cerebral Cortex

Volumn 27, Issue 8, 2017, Pages 4257-4266

  Karjalainen, Tomi ^a   Karlsson, Henry K ^a   Lahnakoski, Juha M ^b,c   Glerean, Enrico ^a,b   Nuutila, Pirjo ^a   Jääskeläinen, Iiro P ^b   Hari, Riitta ^b   Sams, Mikko ^b   Nummenmaa, Lauri ^a,d  

^a TURKU UNIVERSITY HOSPITAL   (Finland)

^b AALTO UNIVERSITY   (Finland)

^c MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

^d UNIVERSITY OF TURKU   (Finland)

Author keywords

Carfentanil; Empathy; Neurotransmitters; Observed pain; Raclopride

Indexed keywords

DOPAMINE 2 RECEPTOR; MU OPIATE RECEPTOR; CARFENTANIL; DRD2 PROTEIN, HUMAN; FENTANYL; OPRM1 PROTEIN, HUMAN; OXYGEN; RACLOPRIDE; RADIOPHARMACEUTICAL AGENT;

ADULT; ARTICLE; BRAIN REGION; CLINICAL ARTICLE; FEMALE; FUNCTIONAL MAGNETIC RESONANCE IMAGING; FUNCTIONAL NEUROIMAGING; HAND PAIN; HUMAN; IMAGE ANALYSIS; IN VIVO STUDY; MALE; MEDICAL HISTORY; PAIN; PET-CT SCANNER; POSITRON EMISSION TOMOGRAPHY; PRIMARY MOTOR CORTEX; PRIORITY JOURNAL; SUPERIOR TEMPORAL SULCUS; VICARIOUS PAIN; ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; BLOOD; BRAIN; BRAIN CIRCULATION; BRAIN MAPPING; DIAGNOSTIC IMAGING; DRUG EFFECTS; EMPATHY; METABOLISM; MIDDLE AGED; MULTIMODAL IMAGING; NOCICEPTION; NUCLEAR MAGNETIC RESONANCE IMAGING; PERCEPTION; PHYSIOLOGY; VISION; YOUNG ADULT;

ADULT; BRAIN; BRAIN MAPPING; CEREBROVASCULAR CIRCULATION; EMPATHY; FEMALE; FENTANYL; HUMANS; MAGNETIC RESONANCE IMAGING; MIDDLE AGED; MULTIMODAL IMAGING; OXYGEN; PAIN PERCEPTION; POSITRON-EMISSION TOMOGRAPHY; RACLOPRIDE; RADIOPHARMACEUTICALS; RECEPTORS, DOPAMINE D2; RECEPTORS, OPIOID, MU; SOCIAL PERCEPTION; VISUAL PERCEPTION; YOUNG ADULT;

EID: 85026512317     PISSN: 10473211     EISSN: 14602199     Source Type: Journal    
DOI: 10.1093/cercor/bhx129     Document Type: Article

References (70)

1. Alenius S, Ruotsalainen U. 1997. Bayesian image reconstruction for emission tomography based on median root prior. Eur J Nucl Med. 24:258-265.
2. Bencherif B, Fuchs PN, Sheth R, Dannals RF, Campbell JN, Frost JJ. 2002. Pain activation of human supraspinal opioid pathways as demonstrated by C-11-carfentanil and positron emission tomography (PET). Pain. 99:589-598.
3. Bos PA, Montoya ER, Hermans EJ, Keysers C, van Honk J. 2015. Oxytocin reduces neural activity in the pain circuitry when seeing pain in others. Neuroimage. 113:217-224.
4. Bufalari I, Aprile T, Avenanti A, Di Russo F, Aglioti SM. 2007. Empathy for pain and touch in the human somatosensory cortex. Cerebral Cortex (New York, NY: 1991). 17:2553-2561.
5. Çukur T, Nishimoto S, Huth AG, Gallant JL. 2013. Attention during natural vision warps semantic representation across the human brain. Nat Neurosci. 16:763-770.
6. Danziger N, Prkachin KM, Willer JC. 2006. Is pain the price of empathy? The perception of others' pain in patients with congenital insensitivity to pain. Brain. 129:2494-2507.
7. Derbyshire SW, Osborn J, Brown S. 2013. Feeling the pain of others is associated with self-other confusion and prior pain experience. Front Hum Neurosci. 7:470.
8. Eklund A, Nichols TE, Knutsson H. 2016. Cluster failure: why fMRI inferences for spatial extent have inflated falsepositive rates. Proc Natl Acad Sci USA. 113:7900-7905.
9. Friston KJ, Williams S, Howard R, Frackowiak RS, Turner R. 1996. Movement-related effects in fMRI time-series. Magn Reson Med. 35:346-355.
10. Gabilondo AM, Meana JJ, García-Sevilla JA. 1995. Increased density of mu-opioid receptors in the postmortem brain of suicide victims. Brain Res. 682:245-250.
11. Grossman M, Wood W. 1993. Sex differences in intensity of emotional experience: a social role interpretation. J Pers Soc Psychol. 65:1010-1022.
12. Gunn RN, Lammertsma AA, Hume SP, Cunningham VJ. 1997. Parametric imaging of ligand-receptor binding in PET using a simplified reference region model. Neuroimage. 6:279-287.
13. Hagelberg N, Aalto S, Tuominen L, Pesonen U, Nagren K, Hietala J, Scheinin H, Pertovaara A, Martikainen IK. 2012. Striatal muopioid receptor availability predicts cold pressor pain threshold in healthy human subjects. Neurosci Lett. 521:11-14.
14. Hagelberg N, Martikainen IK, Mansikka H, Hinkka S, Nagren K, Hietala J, Scheinin H, Pertovaara A. 2002. Dopamine D2 receptor binding in the human brain is associated with the response to painful stimulation and pain modulatory capacity. Pain. 99:273-279.
15. Hein G, Silani G, Preuschoff K, Batson CD, Singer T. 2010. Neural responses to ingroup and outgroup members' suffering predict individual differences in costly helping. Neuron. 68:149-160.
16. Heinricher M, Fields H. 2013. Central nervous system mechanisms of pain modulation. In: McMahon S, Koltzenburg M, Tracey I, Turk DC, editors. Wall and Melzack's Textbook of Pain. 6th ed. Philadelphia, PA: Elsevier.
17. Hietala J, Nagren K, Lehikoinen P, Ruotsalainen U, Syvälahti E. 1999. Measurement of striatal D2 dopamine receptor density and affinity with [11C]-raclopride in vivo: a test-retest analysis. J Cereb Blood Flow Metabol. 19:210-217.
18. Hirvonen J, Aalto S, Hagelberg N, Maksimow A, Ingman K, Oikonen V, Virkkala J, Nagren K, Scheinin H. 2009. Measurement of central mu-opioid receptor binding in vivo with PET and [11C]carfentanil: a test-retest study in healthy subjects. Eur J Nucl Med Mol Imaging. 36:275-286.
19. Jackson PL, Brunet E, Meltzoff AN, Decety J. 2006. Empathy examined through the neural mechanisms involved in imagining how I feel versus how you feel pain. Neuropsychologia. 44:752-761.
20. Jackson PL, Meltzoff AN, Decety J. 2005. How do we perceive the pain of others? A window into the neural processes involved in empathy. Neuroimage. 24:771-779.
21. Johansson J, Alakurtti K, Joutsa J, Tohka J, Ruotsalainen U, Rinne JO. 2016. Comparison of manual and automatic techniques for substriatal segmentation in 11C-raclopride highresolution PET studies. Nucl Med Commun. 37:1074-1087.
22. Karjalainen T, Tuominen L, Manninen S, Kalliokoski KK, Nuutila P, Jääskeläinen IP, Hari R, Sams M, Nummenmaa L. 2016. Behavioural activation system sensitivity is associated with cerebral μ-opioid receptor availability. Soc Cogn Affect Neurosci. 11:1310-1316.
23. Karlsson HK, Tuominen L, Tuulari JJ, Hirvonen J, Parkkola R, Helin S, Salminen P, Nuutila P, Nummenmaa L. 2015. Obesity is associated with decreased mu-opioid but unaltered dopamine D-2 receptor availability in the brain. J Neurosci. 35:3959-3965.
24. Krishnan A, Woo C-W, Chang LJ, Ruzic L, Gu X, López-Solà M, Jackson PL, Pujol J, Fan J, Wager TD. 2016. Somatic and vicarious pain are represented by dissociable multivariate brain patterns. eLife. 5:e15166.
25. Lahnakoski JM, Glerean E, Salmi J, Jääskeläinen I, Sams M, Hari R, Nummenmaa L. 2012. Naturalistic fMRI mapping reveals superior temporal sulcus as the hub for the distributed brain network for social perception. Front Hum Neurosci. 6:14.
26. Lamm C, Decety J, Singer T. 2011. Meta-analytic evidence for common and distinct neural networks associated with directly experienced pain and empathy for pain. Neuroimage. 54:2492-2502.
27. Lammertsma AA, Hume SP. 1996. Simplified reference tissue model for PET receptor studies. Neuroimage. 4:153-158.
28. Liberzon I, Zubieta JK, Fig LM, Phan KL, Koeppe RA, Taylor SF. 2002. μ-Opioid receptors and limbic responses to aversive emotional stimuli. Proc Natl Acad Sci USA. 99:7084-7089.
29. Lin MT, Wu JJ, Chandra A, Tsay BL. 1981. Activation of striatal dopamine receptors induces pain inhibition in rats. J Neural Transm. 51:213-222.
30. Magnusson JE, Fisher K. 2000. The involvement of dopamine in nociception: the role of D1 and D2 receptors in the dorsolateral striatum. Brain Res. 855:260-266.
31. Manninen S, Tuominen L, Dunbar RIM, Karjalainen T, Hirvonen J, Arponen E, Hari R, Jääskeläinen IP, Sams M, Nummenmaa L. 2017. Social laughter triggers endogenous opioid release in humans. J Neurosci. forthcoming.
32. Martikainen IK, Hagelberg N, Mansikka H, Hietala J, Nagren K, Scheinin H, Pertovaara A. 2005. Association of striatal dopamine D2/D3 receptor binding potential with pain but not tactile sensitivity or placebo analgesia. Neurosci Lett. 376:149-153.
33. Martikainen IK, Nuechterlein EB, Peciña M, Love TM, Cummiford CM, Green CR, Stohler CS, Zubieta JK. 2015. Chronic back pain is associated with alterations in dopamine neurotransmission in the ventral striatum. J Neurosci. 35:9957-9965.
34. Mischkowski D, Crocker J, Way BM. 2016. From painkiller to empathy killer: acetaminophen (paracetamol) reduces empathy for pain. Soc Cogn Affect Neurosci. 11:1345-1353.
35. Moles A, Kieffer BL, D'Amato FR. 2004. Deficit in attachment behavior in mice lacking the mu-opioid receptor gene. Science. 304:1983-1986.
36. Morelli SA, Rameson LT, Lieberman MD. 2014. The neural components of empathy: predicting daily prosocial behavior. Soc Cogn Affect Neurosci. 9:39-47.
37. Morishima Y, Schunk D, Bruhin A, Ruff CC, Fehr E. 2012. Linking brain structure and activation in temporoparietal junction to explain the neurobiology of human altruism. Neuron. 75:73-79.
38. Nordström AL, Farde L, Pauli S, Litton JE, Halldin C. 1992. PET analysis of central [11C]raclopride binding in healthy young adults and schizophrenic patients-reliability and age effects. Hum Psychopharmacol Clin Exp. 7:157-165.
39. Nummenmaa L, Calder AJ. 2009. Neural mechanisms of social attention. Trends Cogn Sci. 13:135-143.
40. Nummenmaa L, Manninen S, Tuominen L, Hirvonen J, Kalliokoski KK, Nuutila P, Jääskeläinen IP, Hari R, Dunbar RI, Sams M. 2015. Adult attachment style is associated with cerebral mu-opioid receptor availability in humans. Hum Brain Mapp. 36:3621-3628.
41. Nummenmaa L, Tuominen L. 2017. Opioid system and human emotions. Br J Pharmacol. forthcoming.
42. Panksepp J, Herman BH, Vilberg T, Bishop P, Deeskinazi FG. 1980. Endogenous opioids and social behaviour. Neurosci Biobehav Rev. 4:473-487.
43. Peciña M, Love T, Stohler CS, Goldman D, Zubieta JK. 2015. Effects of the mu opioid receptor polymorphism (OPRM1 A118G) on pain regulation, placebo effects and associated personality trait measures. Neuropsychopharmacology. 40: 957-965.
44. Peciña M, Zubieta JK. 2015. Molecular mechanisms of placebo responses in humans. Mol Psychiatry. 20:416-423.
45. Pertovaara A, Martikainen IK, Hagelberg N, Mansikka H, Nagren K, Hietala J, Scheinin H. 2004. Striatal dopamine D2/D3 receptor availability correlates with individual response characteristics to pain. Eur J Neurosci. 20:1587-1592.
46. Powell J, Lewis PA, Roberts N, García-Fiñana M, Dunbar RIM. 2012. Orbital prefrontal cortex volume predicts social network size: an imaging study of individual differences in humans. Proc R Soc B Biol Sci. 279:2157-2162.
47. Price DD. 2000. Psychological and neural mechanisms of the affective dimension of pain. Science. 288:1769-1772.
48. Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC. 1997. Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science. 277:968-971.
49. Rameson LT, Morelli SA, Lieberman MD. 2012. The neural correlates of empathy: experience, automaticity, and prosocial behavior. J Cogn Neurosci. 24:235-245.
50. Robinson ME, Wise EA. 2003. Gender bias in the observation of experimental pain. Pain. 104:259-264.
51. Rütgen M, Seidel EM, Riečanský I, Lamm C. 2015. Reduction of empathy for pain by placebo analgesia suggests functional equivalence of empathy and first-hand emotion experience. J Neurosci. 35:8938-8947.
52. Rütgen M, Seidel EM, Silani G, Riečanský I, Hummer A, Windischberger C, Petrovic P, Lamm C. 2015. Placebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain. Proc Natl Acad Sci USA. 112: E5638-E5646.
53. Saarela MV, Hlushchuk Y, Williams AC, Schürmann M, Kalso E, Hari R. 2007. The compassionate brain: humans detect intensity of pain from another's face. Cerebral Cortex (New York, NY: 1991). 17:230-237.
54. Schurz M, Radua J, Aichhorn M, Richlan F, Perner J. 2014. Fractionating theory of mind: a meta-analysis of functional brain imaging studies. Neurosci Biobehav Rev. 42:9-34.
55. Scott DJ, Heitzeg MM, Koeppe RA, Stohler CS, Zubieta JK. 2006. Variations in the human pain stress experience mediated by ventral and dorsal basal ganglia dopamine activity. J Neurosci. 26:10789-10795.
56. Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK. 2008. Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Arch Gen Psychiatry. 65:220-231.
57. Scott DJ, Stohler CS, Koeppe RA, Zubieta JK. 2007. Time-course of change in [11C]carfentanil and [11C]raclopride binding potential after a nonpharmacological challenge. Synapse. 61:707-714.
58. Singer T, Seymour B, O'Doherty J, Kaube H, Dolan RJ, Frith CD. 2004. Empathy for pain involves the affective but not sensory components of pain. Science. 303:1157-1162.
59. Singer T, Seymour B, O'Doherty JP, Stephan KE, Dolan RJ, Frith CD. 2006. Empathic neural responses are modulated by the perceived fairness of others. Nature. 439:466-469.
60. Smith YR, Stohler CS, Nichols TE, Bueller JA, Koeppe RA, Zubieta JK. 2006. Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. J Neurosci. 26:5777-5785.
61. Taylor AM, Becker S, Schweinhardt P, Cahill C. 2016. Mesolimbic dopamine signaling in acute and chronic pain: implications for motivation, analgesia, and addiction. Pain. 157:1194-1198.
62. Taylor BK, Joshi C, Uppal H. 2003. Stimulation of dopamine D2 receptors in the nucleus accumbens inhibits inflammatory pain. Brain Res. 987:135-143.
63. Tracey I, Mantyh PW. 2007. The cerebral signature for pain perception and its modulation. Neuron. 55:377-391.
64. Tuominen L, Nummenmaa L, Keltikangas-Järvinen L, Raitakari O, Hietala J. 2014. Mapping neurotransmitter networks with PET: an example on serotonin and opioid systems. Hum Brain Mapp. 35:1875-1884.
65. Wager TD, Scott DJ, Zubieta JK. 2007. Placebo effects on human mu-opioid activity during pain. Proc Natl Acad Sci USA. 104: 11056-11061.
66. Wood PB, Schweinhardt P, Jaeger E, Dagher A, Hakyemez H, Rabiner EA, Bushnell MC, Chizh BA. 2007. Fibromyalgia patients show an abnormal dopamine response to pain. Eur J Neurosci. 25:3576-3582.
67. Zubieta JK, Smith YR, Bueller JA, Xu Y, Kilbourn MR, Jewett DM, Meyer CR, Koeppe RA, Stohler CS. 2002. μ-opioid receptormediated antinociceptive responses differ in men and women. J Neurosci. 22:5100-5107.
68. Zubieta JK, Dannals RF, Frost JJ. 1999. Gender and age influences on human brain mu-opioid receptor binding measured by PET. Am J Psychiatry. 156:842-848.
69. Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu YJ, Koeppe RA, Stohler CS, Goldman D. 2003. COMT val(158)met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 299:1240-1243.
70. Zubieta JK, Smith YR, Bueller JA, Xu YJ, Kilbourn MR, Jewett DM, Meyer CR, Koeppe RA, Stohler CS. 2001. Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science. 293:311-315.