奖赏与疼痛研究进展及对针刺镇痛研究的启示
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摘要
疼痛在本质上是一种不愉快的体验,具有通过促进动机和学习来保护机体的特征。厌恶状态的缓解(包括疼痛的缓解)是有奖赏性质的。对疼痛的厌恶以及疼痛缓解获得的奖赏,都由具有奖赏/动机特性的中脑-边缘-皮层环路编码。本文综述了一些从动物模型以及人体神经影像研究获得的疼痛机制以及针刺对奖赏/动机环路影响的研究结果。此外,笔者还建议借助神经影像技术追踪介导针刺作用的大脑区域,并将脑奖赏/动机环路对针刺的反应作为一种镇痛功效判定的客观指标,为今后更加深入地研究针刺改善慢性痛的中枢机制提供帮助。
Pain is inherently unpleasant and has the characteristic of protecting the body by promoting motivation and learning.Relief from aversion(including pain relief)is rewarding.The aversion to pain and reward from pain relief are encoded by brain mesocorticolimbic circuits characterized by reward/motivation.This paper reviews the research findings about the effect of pain and acupuncture on reward/motivation circuits derived from animal models and human neuroimaging.It is further suggested that neuroimaging techniques may be used to track brain regions that mediate acupuncture effect,and the response of reward/motivation circuits to acupuncture could be used as an objective indicator of analgesic efficacy.It may provide help for further study on the brain mechanism of acupuncture in improving chronic pain.
Pain is inherently unpleasant and has the characteristic of protecting the body by promoting motivation and learning.Relief from aversion(including pain relief)is rewarding.The aversion to pain and reward from pain relief are encoded by brain mesocorticolimbic circuits characterized by reward/motivation.This paper reviews the research findings about the effect of pain and acupuncture on reward/motivation circuits derived from animal models and human neuroimaging.It is further suggested that neuroimaging techniques may be used to track brain regions that mediate acupuncture effect,and the response of reward/motivation circuits to acupuncture could be used as an objective indicator of analgesic efficacy.It may provide help for further study on the brain mechanism of acupuncture in improving chronic pain.
引文
[1]韩济生.神经科学[M].3版.北京:北京大学医学部出版社,2009:636.
[2]REDGRAVE P,GURNEY K,REYNOLDS J.What is reinforced by phasic dopamine signals[J].Brain Res Rev,2008,58(2):322-339.
[3]PEREIRA F G,FRANCA M H,PAIVA M C A,et al.Prevalence and clinical profile of chronic pain and its association with mental disorders[J].Rev Saude Publica,2017,51:96.
[4]TEGETHOFF M,BELARDI A,STALUJANIS E,et al.Comorbidity of mental disorders and chronic pain:chronology of onset in adolescents of a national representative cohort[J].J Pain,2015,16(10):1054-1064.
[5]WOOLF C J.Central sensitization:implications for the diagnosis and treatment of pain[J].Pain,2011,152(3Suppl):S2-S15.
[6]APKARIAN A V,BALIKI M N,FARMER M A.Predicting transition to chronic pain[J].Curr Opin Neurol,2013,26(4):360-367.
[7]SEIFERT F,MAIHOFNER C.Functional and structural imaging of pain-induced neuroplasticity[J].Curr Opin Anaesthesiol,2011,24(5):515-523.
[8]NAVRATILOVA E,PORRECA F.Reward and motivation in pain and pain relief[J].Nat Neurosci,2014,17(10):1304-1312.
[9]NOONAN M P,MARS R B,RUSHWORTH M F.Distinct roles of three frontal cortical areas in reward-guided behavior[J].J Neurosci,2011,31(40):14399-14412.
[10]BISSONETTE G B,ROESCH M R.Neurophysiology of reward-guided behavior:correlates related to predictions,value,motivation,errors,attention,and action[J].Curr Top Behav Neurosci,2016,27:199-230.
[11]BURSTEIN R,GIESLER G J JR.Retrograde labeling of neurons in spinal cord that project directly to nucleus accumbens of the septal nuclei in the rat[J].Brain Res,1989,497(1):149-154.
[12]GEAR R W,LEVINE J D.Nucleus accumbens facilitates nociception[J].Exp Neurol,2011,229(2):502-506.
[13]SCHULTZ W.Updating dopamine reward signals[J].Curr Opin Neurobiol,2013,23(2):229-238.
[14]BUDYGIN E A,PARK J,BASS C E,et al.Aversive stimulus differentially triggers subsecond dopamine release in reward regions[J].Neuroscience,2012,201:331-337.
[15]BECERRA L,BORSOOK D.Signal valence in the nucleus accumbens to pain onset and offset[J].Eur J Pain,2008,12(7):866-869.
[16]LEVENSON R W.Basic emotion questions[J].Emot Rev,2011,3(2):379-386.
[17]LEKNES S,BROOKS J C,WIECH K,et al.Pain relief as an opponent process:apsychophysical investigation[J].Eur J Neurosci,2008,28(4):794-801.
[18]LEKNES S,LEE M,BERNA C,et al.Relief as a reward:hedonic and neural responses to safety from pain[J].PLoSOne,2011,6(4):e17870.
[19]NAVRATILOVA E,XIE J Y,OKUN A,et al.Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry[J].Proc Natl Acad Sci USA,2012,109(50):20709-20713.
[20]BECERRA L,NAVRATILOVA E,PORRECA F,et al.Analogous responses in the nucleus accumbens and cingulate cortex to pain onset(aversion)and offset(relief)in rats and humans[J].J Neurophysiol,2013,110(5):1221-1226.
[21]GERBER B,YARALI A,DIEGELMANN S,et al.Painrelief learning in flies,rats,and man:basic research and applied perspectives[J].Learn Mem,2014,21(4):232-252.
[22]MOGIL J S.Animal models of pain:progress and challenges[J].Nat Rev Neurosci,2009,10(4):283-294.
[23]MOGIL J S,DAVIS K D,DERBYSHIRE S W.The necessity of animal models in pain research[J].Pain,2010,151(1):12-17.
[24]KING T,VERA-PORTOCARRERO L,GUTIERREZ T,et al.Unmasking the tonic-aversive state in neuropathic pain[J].Nat Neurosci,2009,12(11):1364-1366.
[25]JOHANSEN J P,FIELDS H L,MANNING B H.The affective component of pain in rodents:direct evidence for a contribution of the anterior cingulate cortex[J].Proc Natl Acad Sci USA,2001,98(14):8077-8082.
[26]JOHANSEN J P,FIELDS H L.Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal[J].Nat Neurosci,2004,7(4):398-403.
[27]CAO H,GAO Y J,REN W H,et al.Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction and expression of affective pain[J].J Neurosci,2009,29(10):3307-3321.
[28]LEKNES S,TRACEY I.A common neurobiology for pain and pleasure[J].Nat Rev Neurosci,2008,9(4):314-320.
[29]WANIGASEKERA V,LEE M C,ROGERS R,et al.Baseline reward circuitry activity and trait reward responsiveness predict expression of opioid analgesia in healthy subjects[J].Proc Natl Acad Sci USA,2012,109(43):17705-17710.
[30]SCOTT D J,HEITZEG M M,KOEPPE R A,et al.Variations in the human pain stress experience mediated by ventral and dorsal basal ganglia dopamine activity[J].J Neurosci,2006,26(42):10789-10795.
[31]MARTIKAINEN I K,NUECHTERLEIN E B,PECINA M,et al.Chronic back pain is associated with alterations in dopamine neurotransmission in the ventral striatum[J].J Neurosci,2015,35(27):9957-9965.
[32]DE FELICE M,EYDE N,DODICK D,et al.Capturing the aversive state of cephalic pain preclinically[J].Ann Neurol,2013,74(2):257-265.
[33]XIE J Y,QU C,PATWARDHAN A,et al.Activation of mesocorticolimbic reward circuits for assessment of relief of ongoing pain:apotential biomarker of efficacy[J].Pain,2014,155(8):1659-1666.
[34]HUI K K,LIU J,MAKRIS N,et al.Acupuncture modulates the limbic system and subcortical gray structures of the human brain:evidence from fMRI studies in normal subjects[J].Hum Brain Mapp,2000,9(1):13-25.
[35]HUI K K,LIU J,MARINA O,et al.The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST36as evidenced by fMRI[J].Neuroimage,2005,27(3):479-496.
[36]FANG J,JIN Z,WANG Y,et al.The salient characteristics of the central effects of acupuncture needling:limbic-paralimbic-neocortical network modulation[J].Hum Brain Mapp,2009,30(4):1196-1206.
[37]PARIENTE J,WHITE P,FRACKOWIAK R S,et al.Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture[J].Neuroimage,2005,25(4):1161-1167.
[38]LEE I S,WALLRAVEN C,KONG J,et al.When pain is not only pain:inserting needles into the body evokes distinct rewardrelated brain responses in the context of a treatment[J].Physiol Behav,2015,140:148-155.
[39]KONG J,WANG Z,LEISER J,et al.Enhancing treatment of osteoarthritis knee pain by boosting expectancy:a functional neuroimaging study[J].Neuroimage Clin,2018,18:325-334.
[40]WANG Z,WANG X,LIU J,et al.Acupuncture treatment modulates the corticostriatal reward circuitry in major depressive disorder[J].J Psychiatr Res,2017,84:18-26.
[41]HAN J S.Acupuncture:neuropeptide release produced by electrical stimulation of different frequencies[J].Trends Neurosci,2003,26(1):17-22.
[42]ZHAO Z Q.Neural mechanism underlying acupuncture analgesia[J].Prog Neurobiol,2008,85(4):355-375.
[43]NAVRATILOVA E,XIE J Y,MESKE D,et al.Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain[J].J Neurosci,2015,35(18):7264-7271.
[44]YOSHIOMOTO K,FUKUDA F,HORI M,et al.Acupuncture stimulates the release of serotonin,but not dopamine,in the rat nucleus accumbens[J].Tohoku J Exp Med,2006,208(4):321-326.
[45]闫娅霞,冯秀梅,王俊英,等.电针对慢性痛大鼠痛感觉和情绪成分相关杏仁核内阿片受体等蛋白表达的影响[J].针刺研究,2016,41(1):3-10.
[46]端木程琳,冯秀梅,闫娅霞,等.电针对慢性痛负性情绪大鼠杏仁核神经突触可塑性相关蛋白/基因表达的影响[J].针刺研究,2017,42(1):1-8.
[2]REDGRAVE P,GURNEY K,REYNOLDS J.What is reinforced by phasic dopamine signals[J].Brain Res Rev,2008,58(2):322-339.
[3]PEREIRA F G,FRANCA M H,PAIVA M C A,et al.Prevalence and clinical profile of chronic pain and its association with mental disorders[J].Rev Saude Publica,2017,51:96.
[4]TEGETHOFF M,BELARDI A,STALUJANIS E,et al.Comorbidity of mental disorders and chronic pain:chronology of onset in adolescents of a national representative cohort[J].J Pain,2015,16(10):1054-1064.
[5]WOOLF C J.Central sensitization:implications for the diagnosis and treatment of pain[J].Pain,2011,152(3Suppl):S2-S15.
[6]APKARIAN A V,BALIKI M N,FARMER M A.Predicting transition to chronic pain[J].Curr Opin Neurol,2013,26(4):360-367.
[7]SEIFERT F,MAIHOFNER C.Functional and structural imaging of pain-induced neuroplasticity[J].Curr Opin Anaesthesiol,2011,24(5):515-523.
[8]NAVRATILOVA E,PORRECA F.Reward and motivation in pain and pain relief[J].Nat Neurosci,2014,17(10):1304-1312.
[9]NOONAN M P,MARS R B,RUSHWORTH M F.Distinct roles of three frontal cortical areas in reward-guided behavior[J].J Neurosci,2011,31(40):14399-14412.
[10]BISSONETTE G B,ROESCH M R.Neurophysiology of reward-guided behavior:correlates related to predictions,value,motivation,errors,attention,and action[J].Curr Top Behav Neurosci,2016,27:199-230.
[11]BURSTEIN R,GIESLER G J JR.Retrograde labeling of neurons in spinal cord that project directly to nucleus accumbens of the septal nuclei in the rat[J].Brain Res,1989,497(1):149-154.
[12]GEAR R W,LEVINE J D.Nucleus accumbens facilitates nociception[J].Exp Neurol,2011,229(2):502-506.
[13]SCHULTZ W.Updating dopamine reward signals[J].Curr Opin Neurobiol,2013,23(2):229-238.
[14]BUDYGIN E A,PARK J,BASS C E,et al.Aversive stimulus differentially triggers subsecond dopamine release in reward regions[J].Neuroscience,2012,201:331-337.
[15]BECERRA L,BORSOOK D.Signal valence in the nucleus accumbens to pain onset and offset[J].Eur J Pain,2008,12(7):866-869.
[16]LEVENSON R W.Basic emotion questions[J].Emot Rev,2011,3(2):379-386.
[17]LEKNES S,BROOKS J C,WIECH K,et al.Pain relief as an opponent process:apsychophysical investigation[J].Eur J Neurosci,2008,28(4):794-801.
[18]LEKNES S,LEE M,BERNA C,et al.Relief as a reward:hedonic and neural responses to safety from pain[J].PLoSOne,2011,6(4):e17870.
[19]NAVRATILOVA E,XIE J Y,OKUN A,et al.Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry[J].Proc Natl Acad Sci USA,2012,109(50):20709-20713.
[20]BECERRA L,NAVRATILOVA E,PORRECA F,et al.Analogous responses in the nucleus accumbens and cingulate cortex to pain onset(aversion)and offset(relief)in rats and humans[J].J Neurophysiol,2013,110(5):1221-1226.
[21]GERBER B,YARALI A,DIEGELMANN S,et al.Painrelief learning in flies,rats,and man:basic research and applied perspectives[J].Learn Mem,2014,21(4):232-252.
[22]MOGIL J S.Animal models of pain:progress and challenges[J].Nat Rev Neurosci,2009,10(4):283-294.
[23]MOGIL J S,DAVIS K D,DERBYSHIRE S W.The necessity of animal models in pain research[J].Pain,2010,151(1):12-17.
[24]KING T,VERA-PORTOCARRERO L,GUTIERREZ T,et al.Unmasking the tonic-aversive state in neuropathic pain[J].Nat Neurosci,2009,12(11):1364-1366.
[25]JOHANSEN J P,FIELDS H L,MANNING B H.The affective component of pain in rodents:direct evidence for a contribution of the anterior cingulate cortex[J].Proc Natl Acad Sci USA,2001,98(14):8077-8082.
[26]JOHANSEN J P,FIELDS H L.Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal[J].Nat Neurosci,2004,7(4):398-403.
[27]CAO H,GAO Y J,REN W H,et al.Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction and expression of affective pain[J].J Neurosci,2009,29(10):3307-3321.
[28]LEKNES S,TRACEY I.A common neurobiology for pain and pleasure[J].Nat Rev Neurosci,2008,9(4):314-320.
[29]WANIGASEKERA V,LEE M C,ROGERS R,et al.Baseline reward circuitry activity and trait reward responsiveness predict expression of opioid analgesia in healthy subjects[J].Proc Natl Acad Sci USA,2012,109(43):17705-17710.
[30]SCOTT D J,HEITZEG M M,KOEPPE R A,et al.Variations in the human pain stress experience mediated by ventral and dorsal basal ganglia dopamine activity[J].J Neurosci,2006,26(42):10789-10795.
[31]MARTIKAINEN I K,NUECHTERLEIN E B,PECINA M,et al.Chronic back pain is associated with alterations in dopamine neurotransmission in the ventral striatum[J].J Neurosci,2015,35(27):9957-9965.
[32]DE FELICE M,EYDE N,DODICK D,et al.Capturing the aversive state of cephalic pain preclinically[J].Ann Neurol,2013,74(2):257-265.
[33]XIE J Y,QU C,PATWARDHAN A,et al.Activation of mesocorticolimbic reward circuits for assessment of relief of ongoing pain:apotential biomarker of efficacy[J].Pain,2014,155(8):1659-1666.
[34]HUI K K,LIU J,MAKRIS N,et al.Acupuncture modulates the limbic system and subcortical gray structures of the human brain:evidence from fMRI studies in normal subjects[J].Hum Brain Mapp,2000,9(1):13-25.
[35]HUI K K,LIU J,MARINA O,et al.The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST36as evidenced by fMRI[J].Neuroimage,2005,27(3):479-496.
[36]FANG J,JIN Z,WANG Y,et al.The salient characteristics of the central effects of acupuncture needling:limbic-paralimbic-neocortical network modulation[J].Hum Brain Mapp,2009,30(4):1196-1206.
[37]PARIENTE J,WHITE P,FRACKOWIAK R S,et al.Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture[J].Neuroimage,2005,25(4):1161-1167.
[38]LEE I S,WALLRAVEN C,KONG J,et al.When pain is not only pain:inserting needles into the body evokes distinct rewardrelated brain responses in the context of a treatment[J].Physiol Behav,2015,140:148-155.
[39]KONG J,WANG Z,LEISER J,et al.Enhancing treatment of osteoarthritis knee pain by boosting expectancy:a functional neuroimaging study[J].Neuroimage Clin,2018,18:325-334.
[40]WANG Z,WANG X,LIU J,et al.Acupuncture treatment modulates the corticostriatal reward circuitry in major depressive disorder[J].J Psychiatr Res,2017,84:18-26.
[41]HAN J S.Acupuncture:neuropeptide release produced by electrical stimulation of different frequencies[J].Trends Neurosci,2003,26(1):17-22.
[42]ZHAO Z Q.Neural mechanism underlying acupuncture analgesia[J].Prog Neurobiol,2008,85(4):355-375.
[43]NAVRATILOVA E,XIE J Y,MESKE D,et al.Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain[J].J Neurosci,2015,35(18):7264-7271.
[44]YOSHIOMOTO K,FUKUDA F,HORI M,et al.Acupuncture stimulates the release of serotonin,but not dopamine,in the rat nucleus accumbens[J].Tohoku J Exp Med,2006,208(4):321-326.
[45]闫娅霞,冯秀梅,王俊英,等.电针对慢性痛大鼠痛感觉和情绪成分相关杏仁核内阿片受体等蛋白表达的影响[J].针刺研究,2016,41(1):3-10.
[46]端木程琳,冯秀梅,闫娅霞,等.电针对慢性痛负性情绪大鼠杏仁核神经突触可塑性相关蛋白/基因表达的影响[J].针刺研究,2017,42(1):1-8.