바로가기메뉴

본문 바로가기 주메뉴 바로가기

ACOMS+ 및 학술지 리포지터리 설명회

  • 한국과학기술정보연구원(KISTI) 서울분원 대회의실(별관 3층)
  • 2024년 07월 03일(수) 13:30
 

logo

뇌의 항유해 작용 기제에 관한 개관: 편도체-뇌간 회로를 중심으로

Review on Amygdala-Brainstem Neural Circuitry of Antinociception

한국심리학회지: 인지 및 생물 / The Korean Journal of Cognitive and Biological Psychology, (P)1226-9654; (E)2733-466X
2008, v.20 no.2, pp.73-94
https://doi.org/10.22172/cogbio.2008.20.2.003
신맹식 (중앙대학교)
  • 다운로드 수
  • 조회수

초록

위협적인 환경에 노출되는 유기체는 흔히 유해자극에 대한 통각민감성을 감소시킨다. 본 리뷰의 목적은 지금까지 축적되어온 신경생물학적, 신경심리학적 증거를 통합하여 편도체-뇌간의 항유해 작용 기제에 대한 포괄적인 이해를 도모하기 위함이다. 하행성 항유해 작용에 중심적인 역할을 하는 뇌 부위는 PAG 및 RVM을 포함하는 뇌간 영역이다. 편도체는 신경해부학 및 기능적으로 이들 뇌간 영역에 연결되어 있다. 공포자극에 의해 편도체 자신이 활성화되면 차례로 이들 뇌간 영역도 활성화되어 결국 통각감소로 이어진다. 항유해 작용과 관련하여 편도체-뇌간 회로의 신경과학적 토대는 주로 아편물질과 비아편물질 간의 상호작용이다. 본 리뷰는 특히 이 뇌 회로에서 항유해 작용을 담당하는 신경세포의 활성 수준이 주로 뮤 아편물질에 의해 조절되는 억제성 (GABA) 시냅스와, 글루타민, 뉴로텐신 또는 VIP 등의 흥분성 시냅스 간의 신경통합의 결과에 의해 결정된다고 제안한다. 더 나아가 본 저자는, 설치류의 보다 보편적인 공포반응인 동결반응의 측정으로부터 얻어진 주요한 실험적 관찰에 비추어, 편도체의 항유해 작용 기제에 대한 최근의 연구들로부터 얻어진 발견의 의의를 논한다.

keywords
공포, 항유해 작용, 편도체, 뇌간, 비아편물질, 신경회로, fear, antinociception, amygdala, brainstem, non-opioid, neural circuitry., fear, antinociception, amygdala, brainstem, non-opioid, neural circuitry.

Abstract

Exposure of organisms to a threatening environment often reduces their pain sensitivity to peripheral nociceptive stimulation. The present review was processed based on a considerable amount of existing neurobiological/psychological evidence to provide a comprehensive understanding of the amygdala-brainstem neural mechanisms of the stress-induced antinociception. Brainstem areas including the PAG and the RVM are critical for descending antinociception. The amygdala is neuroanatomically and functionally connected to these brainstem areas. Stimulation of the amygdala cells following presentation of fear-inducing stimuli to organisms activates the descending antinociceptive system of the brainstem, leading to inhibition of pain. Antinociception is now believed to arise from interactions between opioid and non-opioid synapses in this brain circuitry. Notably, the activity of an antinociceptive cell in this brain circuitry is suggested to be determined by a fine balance, or neural integration between excitatory (i.e., glutamatergic, neurotensinergic, or VIPergic) input and mu-opioid regulated inhibitory (i.e., GABAergic) input onto this cell. The author further discussed some implications of recent observations on amygdala antinociceptive mechanisms, via reflecting them onto findings from studies on other fear responses including freezing in the rodent.

keywords
공포, 항유해 작용, 편도체, 뇌간, 비아편물질, 신경회로, fear, antinociception, amygdala, brainstem, non-opioid, neural circuitry., fear, antinociception, amygdala, brainstem, non-opioid, neural circuitry.

참고문헌

1.

서동오, 이연경, 최준식 (2006). 공포의 생성과 소멸: 파블로프 공포조건화의 뇌회로를 중심으로. 한국심리학회지:실험, 18(1), 1-19.

2.

Adams, J. U., Chen, X., DeRiel, J. K., Adler, M. W., & Liu-Chen, L.-Y. (1994). Intracerebroventricular treatment with an antisense oligodeoxynucleotide to kappa-opioid receptors inhibited kappa-agonist-induced analgesia in rats. Brain Research, 667, 129-132.

3.

Akil, H., Mayer, D. J., & Liebeskind, J. C. (1976). Antagonism of stimulation-produced analgesia by naloxone, a narcotic antagonist. Science, 191, 961-962.

4.

Atweh, S. F., & Kuhar, M. J. (1977). Autoradiographic localization of opiate receptors in rat brain III. The telencephalon. Brain Research, 134, 393-405.

5.

Basbaum, A. I., & Fields, H.L. (1978). Endogenous pain control mechanisms: Review and hypothesis. Annals of Neurology, 4, 451-462.

6.

Basbaum, A. I., & Fields, H. L. (1984). Endogenous pain control systems: Brainstem spinal pathways and endorphin circuitry. Annual Review of Neuroscience, 7, 309-338.

7.

Behbehani, M. M., & Pert, A. (1984). A mechanism for the analgesic effect of neurotensin as revealed by behavioral and electrophysiological techniques. Brain Research, 324, 35-42.

8.

Bellgowan, P.S., & Helmstetter, F.J. (1998). The role of mu and kappa opioid receptors within the periaqueductal gray in the expression of conditional hypoalgesia. Brain Research, 279, 83-89.

9.

Blair, H.T., Schafe, G.E., Bauer, E.P., Rodrigues, S.M., & LeDoux, J.E. (2001). Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning. Learning & Memory, 8, 229-242.

10.

Bolles, R.C., & Fanselow, M.S. (1980). A perceptual-defensive-recuperative model of fear and pain. Behavioral Brain Science, 3, 291-301.

11.

Campeau, S. & Davis, M. (1995). Involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained currently with auditory and visual conditioned stimuli. Journal of Neuroscience, 15, 2301-2311.

12.

Carlson, N.R. (2002). Learning and Memory. Foundations of Physiological Psychology (5th Ed.), pp.355-395. Allyn and Bacon, MA: A Person Education Company.

13.

Carstens, E., & Douglass, D. K. (1995). Midbrain suppression of limb withdrawal and tail flick reflexes in the rat: Correlates with descending inhibition of sacral spinal neurons. Journal of Neurophysiology, 73(6), 2179-2194.

14.

Chen, Y., Mestek, A., Liu, J., Hurley, J.A.,& Yu, L. (1993). Molecular cloning and functional expression of a mu-opioid receptor from rat brain. Molecular Pharmacology, 44, 8-12.

15.

Chien, C. C., Brown, G., Pan, Y.-X., & Pasternak, G.W. (1994). Blockade of U50,488H analgesia by antisense oligodeoxynucleotides to a kappa-opioid receptor. European Journal of Pharmacology, 253, R7-R8.

16.

Collins, D. R., & Pare, D. (1999). Reciprocal changes in the firing probabilities lateral and central medial amygdala neurons. Journal of Neuroscience, 19(2), 836-844.

17.

Connell, K., Bolton, N., Olsen, D., Piomelli, D., & Hohmann A. G. (2006). Role of the basolateral nucleus of the amygdala in endocannabinoid-mediated stress-induced analgesia. Neuroscience letters, 397, 180-184.

18.

Dodd, J., Kelly, J. S., & Said, S. I. (1979). Excitation of CA1 neurons of the rat hippocampus by the octapeptide vasoactive intestinal polypeptide (VIP). British Journal of Pharmacology, 66(1), 125.

19.

Elphick, M. R., & Egartova, M. (2001). The neurobiology and evolution of cannabinoid signalling. Philosophical Transactions of the Royal Society of Lond, Series B, Biological Sciences, 356, 381-408.

20.

Fanselow, M. S., & Helmstetter, F. J. (1988). Conditional analgesia, defensive freezing and benzodiazepines. Behavioral Neuroscience, 102, 233-243.

21.

Fendt, M., Fanselow, M. S., & Koch, M. (2005). Lesions of the dorsal hippocampus block trance fear conditioned potentiation of startle. Behavioral Neuroscience, 119, 834-838.

22.

Fields, H.L., Heinricher, M.M., & Mason, P. (1991). Neurotransmitters in nociceptive modulatory circuits. Annual Review of Neuroscience, 14, 219-245.

23.

Foo, H., & Helmstetter, F.J. (1999). Hypoalgesia elicited by a conditioned stimulus is blocked by a mu, but not a delta or a kappa, opioid antagonist injected into the rostal ventromedial medulla. Pain, 83, 427-431.

24.

Foo, H., & Helmstetter, F. J. (2000). Expression of antinociception in response to a signal for shock is blocked after selective downregulation of mu-opioid receptors in the rostral ventromedial medulla. Molecular Brain Research, 76(2), 282-288.

25.

Gray, T. S., & Magnuson, D. J. (1992). Peptide immunoreactive neurons in the amygdala and the bed nucleus of the stria terminalis project to the midbrain central gray in the rat. Peptides, 13, 451-460.

26.

Guarraci F.A., Frohardt R. J., Kapp B. S. (1999). Amygdaloid D1 dopamine receptor involvement in Pavlovian fear conditioning. Brain Research, 827, 28-40.

27.

Hasanein, P., Parviz., M., Keshavarz., M., & Javanmardi., K. (2007). CB1 receptor activation in the basolateral amygdala produces antinociception in animal models of acute and tonic nociception. Clinical and Experimental Pharmacology & Physiology, 34, 439-449.

28.

Heinricher, M. M., & Kaplan, H. J. (1991). GABA-mediated inhibition in rostral ventromedial medulla: role in nociceptive modulation in the lightly anesthetized rat. Pain, 47, 105-113.

29.

Helmstetter, F. J. (1992). The amygdala is essential for the expression of conditional hypoalgesia. Behavioral Neuroscience, 106(3), 518-528.

30.

Helmstetter, F. J., & Bellgowan, P. S. (1993). Lesions of the amygdala block conditional hypoalgesia on the tail flick test. Brain Research, 612, 253-257.

31.

Helmstetter, F. J., & Bellgowan, P. S. (1994). Hypoalgesia in response to sensitization during acute noise stress. Behavioral Neuroscience, 108(1), 177-185.

32.

Helmstetter, F. J., Bellgowan, P. S. F,. & Poore, L. H. (1995). Microinfusion of mu but not delta or kappa agonists into the basolateral amygdala results in inhibition of the tail flick reflex in pentobarbital-anesthetized rats. Journal of Pharmacology & Experimental Therapeutics, 275, 381-388.

33.

Helmstetter, F. J., Bellgowan, P .S. F., & Tershner, S. A. (1993). Inhibition of the tail flick reflex following microinjections of morphine into the amygdala. NeuroReport, 4, 471-474.

34.

Helmstetter, F. J. & Fanslow, M. S. (1987). Effects of naltrexone on the learning and performance of conditional fear-induced freezing and opioid analgesia. Physiology & Behavior, 39, 501-505.

35.

Helmstetter, F. J., & Landeira-Fernandez, J. (1990). Conditional hypoalgesia is attenuated by naltrexone applied to the periaqueductal gray. Brain Research, 537, 88-92.

36.

Helmstetter, F. J., & Tershiner, S. A. (1994). Lesions of the periaqueductal gray and rostral ventromedial medulla disrupt antinociception but not cardiovascular aversive conditional responses. Journal of Neuroscience, 14(11), 7099-7108.

37.

Helmstetter, F. J., Tershner, S.A., Poore, L. H., & Bellgowan, P. S. F. (1998). Antinociception following opioid stimulation of the basolateral amygdala is expressed through the periaqueductal gray and rostral ventromedial medulla. Brain Research, 779, 104-118.

38.

Hopkins, D. A., & Holstege, G. (1978). Amygdaloid projections to the mesencephalon, pons and medulla oblongata in the cat. Experimental Brain Research, 32, 529-547.

39.

Kalivas, P.W., Gau, B.A., Nemeroff, C.B., & Prange, A.J., Jr. (1982). Antinociception after microinjection of neurotensin into the central amygdaloid nucleus of the rat. Brain Research, 243, 279-286.

40.

Kalyuzhny, A.E., & Wessendorf, M.W. (1998). Relationship of mu- and delta-opioid receptors to GABAergic neurons in the central nervous system, including antinociceptive brainstem circuits. The Journal of Comparative Neurology, 392, 528-547.

41.

Kim, M., Campeau S., Falls, W.A., Davis, M. (1993). Infusion of the non-NMDA receptor antagonist CNQX into the amygdala blocks the expression of fear-potentiated startle. Behavioral and Neural Biology, 59, 5-8.

42.

Law, P.Y. (1995). G-protein and opioid receptors' function. In The Pharmacology of Opioid Peptides, Ed. by LF Tseng, pp. 109-130, Hardwood Academic Publishers, Chur, Switzerland.

43.

LeDoux, J.E. (1992). Brain mechanisms of emotion and emotional learning. Current Opinion in Neurobiology, 2, 191-197.

44.

LeDoux, J.E. (1993). Emotional memory systems in the brain. Behavioral Brain Research, 58, 69-79.

45.

Lee, H.J., Choi, J.-S., Brown, T.-H., & Kim, J. J. (2001). Amygdalar NMDA receptors are critical for the expression of multiple conditioned fear responses. Journal of Neuroscience, 21(11), 4116-4124.

46.

Li, A. H., Hwang, H. M., Tan, P. P., Wu, T., & Wang, H.L. (2001). Neurotensin excites periaqueductal gray neurons projecting to the rostral ventromedial medulla. Journal of Neurophysiology, 85(4), 1479-1488.

47.

Lichtman, A. H., & Fanselow, M.S. (1990). Cats produce analgesia in rats in the tail-flick test: Naltrexone sensitivity is determined by the nociceptive test stimulus. Brain Research, 533, 91-94.

48.

Liebeskind, J. C., Guillbaud, G., Besson, J.M., & Oliveras, J. L. (1973). Analgesia from electrical stimulation of the periaqueductal gray matter in the cat: behavioral observations and inhibitory effects on spinal cord interneurons. Brain Research, 50, 441-446.

49.

Ma Q.P., & Han J.S. (1991). Naloxone blocks the release of opioid peptides in periaqueductal gray and n. accumbens induced by intra-amygdaloid injection of morphine. Peptides 12, 1235-1238.

50.

Manning, B. H., Martin, W.J., & Meng, I. D. (2003). The rodent amygdala contributes to the production of cannabinoid-induced antinociception. Neuroscience, 120, 1157-1170.

51.

Mansour A, Khachaturian H, Lewis ME., Akil H., & Watson SJ. (1987). Autoradiographic differentiation of mu, delta and kappa opioid receptors in the rat forebrain and midbrain. Journal of Neuroscience, 7, 2445-2464.

52.

Maren, S. (2001). Neurobiology of Pavlovian fear conditioning. Annual Review of Neuroscience, 24, 897-931.

53.

Mayer, D. J., & Liebeskind, J.C. (1974). Pain reduction by focal electrical stimulation of the brain: an anatomical and behavioral analysis. Brain Research, 68, 73-93.

54.

McEchron, M. D., Bouwmeester, H., Tseng, W., Weiss, C., & Disterhoft, J. F. (1998). Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat. Hippocampus, 8, 638-646.

55.

McGaraughty, S., Farr, D.A., & Heinricher, M.M. (2004). Lesions of the periaqueductal gray disrupt input to the rostral ventromedial medulla following microinjections of morphine into the medial or basolateral nuclei of the amygdala, Brain Research, 1009, 223-227.

56.

Moreau, J-L., & Fields, H. (1986). Evidence for GABA involvement in midbrain control of medullary neurons that modulate nociceptive transmission. Brain Research, 397, 37-46.

57.

Morgan, M. M., Gold, M. S., Liebeskind, J. C., & Stein, C. (1991). Periaqueductal gray stimulation produces a spinally mediated, opioid antinociception for the inflamed hindpaw of the rat. Brain Research, 545, 17-23.

58.

Nader, K., LeDoux, J. E. (1999). Inhibition of the mesoamygdala dopaminergic pathway impairs the retrieval of conditioned fear associations. Behavioral Neuroscience, 113, 891-901.

59.

Niteckam L., & Frotsch, M. (1988). Organization and synaptic interconnections of GABAergic and cholinergic elements in the rat amygdaloid nuclei: Single and double- immunolabelling studies. The Journal of Comparative Neurology, 279, 470-488.

60.

Nose, I., Higashi, H., Inokuchi, H, & Nishi, S. (1991). Synaptic responses of guinea pig and rat central amygdala neurons in vitro. Journal of Neurophysiology, 65(5), 1227-1241.

61.

Oliveira, M. A. & Prado, W. A. (1998). Antinociception induced by stimulating amygdaloid nuclei in rats: changes produced by systemically administered antagonists. Brazilian Journal of Medical and Biological Research, 31, 681-690.

62.

Oliveira, M. A., & Prado, W. A. (2001). Role of PAG in the antinociception evoked from the medial or central amygdala in rats. Brain Research Bulletin, 54(1), 55-63.

63.

Pan, Z. Z (1998). Mu-opposing actions of the kappa-opioid receptor. Trends in Pharmacology and Sciences, 19, 94-98.

64.

Pan, Z.Z., Tershner, S.A., & Fields, H.L. (1997). Cellular mechanism for anti-analgesic action of agonists of the kappa-opioid receptor. Nature, 389, 382-385.

65.

Pare, D., & Smith, Y. (1993). The intercalated cell masses project to the central and medial nuclei of the amygdala in cats. Neuroscience, 57, 1077-1090.

66.

Phillis, J. W., Kirkpatrick, J. R., & Said, S. I. (1978). Vasoactive intestinal peptide excitation of central neurons. Canadian Journal of Physiology & Pharmacology, 56, 337-340.

67.

Poore, L. H., & Helmstetter, F. J. (1994). Forebrain modulation of nociceptive reflex: Effects of GABA antagonists in the amygdala. Society for Neuroscience Abstracts, 20, 767.

68.

Rainie, D. G., Asprodini, E. K., & Shinnick- Gallagher, P. (1991). Excitatory transmission in the basolateral amygdla. Journal of Neurophysiology, 66(3), 986-998.

69.

Reichling, D. B., Kwiat, G. C., & Basbaum, A.I. (1988). Anatomy, physiology and pharmacology of the periaqueductal gray contribution to antinociceptive controls. Progress in Brain Research, 77, 31-46.

70.

Rizvi, T. A., Ennis, M., Behbehani, M. M., & Shipley, M. T. (1991). Connections between the central nucleus of the amygdala and the midbrain periaqueductal gray: Topography and reciprocity. The Journal of Comparative Neurology, 303, 121-131.

71.

Roberts, G. W., & Woodhams, P. L., Polak, J. M., & Crow, T. L. (1982). Distribution of neuropeptides in the limbic system of the rat: The amygdaloid complex. Neuroscience, 7,(1), 99-131.

72.

Rogan, M. T., Staubli, U. V., & LeDoux J. E., (1997). AMPA receptor facilitation accelerates fear learning without altering the level of conditioned fear acquired. Journal of Neuroscience, 17, 5928-5935.

73.

Rudy, J. W. (1996). Scopolamine administered before and after training impairs both contextual and auditory-cue fear conditioning. Neurobiology of Learning and Memory 65, 73-81.

74.

Savander,V., Go, C.-G., LeDoux, J. E. & Pitkanen, A. (1995). Intrinsic connections of the rat amygdaloid complex: Projections originating in the basal nucleus. The Journal of Comparative Neurology, 361, 345-368.

75.

Seo, D.-O., Pang, M.-H., Shin, M.-S., Kim, H.-T., & Choi, J.-S. (2008). Hippocampal NMDA receptors are necessary for auditory trace fear conditioning measured with conditioned hypoalgesia in rats. Behavioral Brain Research (in press).

76.

Shin, M.-S. (2002). Neuropeptide circuitry of the amygdala related to antinociception. Dissertation for Ph.D. at University of Wisconsin- Milwaukee.

77.

Shin, M.-S. (2005). Vasoactive intestinal peptide in the amygdala inhibits tail flick reflexes in rats. Brain Research, 1040, 197-201.

78.

Shin, M.-S., & Helmstetter, F. J. (1998). Effects of selective down-regulation of mu receptors in the basolateral amygdala with antisense oligonucleotides on antinociception. Society for Neuroscience Abstracts, 24, 447.1.

79.

Shin, M.-S., & Helmstetter, F. J. (1999). Modulation of the analgesic effects of mu agonists by acute or chronic manipulation of kappa opioid receptors in the basolateral amygdala. Society for Neuroscience Abstracts, 25, 669.15.

80.

Shin, M.-S, & Helmstetter, F. J. (2000). Pretreatment of the central, but not the basolateral, amygdala with muscimol blocks induction of mu-related antinociception following application of DAMGO. Society for Neuroscience Abstracts, 26, 244.12.

81.

Shin, M.-S., & Helmstetter, F. J. (2001). Vasoactive intestinal peptide interactions with mu opioids in the basolateral amygdala during antinociception. Society for Neuroscience Abstracts, 27, 509.16.

82.

Shin, M.-S., & Helmstetter, F. J. (2005). Antinociception following application of DAMGO to the basolateral amygdala results from a direct interaction of DAMGO with Mu opioid receptors in the amygdala. Brain Research, 1064, 56-65.

83.

Shiosaka, S., Sakanaka, M., Inagaki, S., Senba, E., Hara, Y., Takatsuki, K., Takagim H., Kawai, Y., & Tohyama, M. (1983). Putative neurotransmitters in the amygdaloid complex with special reference to peptidergic pathways. In P.C. Emson (Ed.), Chemical Neuroanatomy, Raven, New York, pp.359- 389.

84.

Smith, B. S., & Millhouse, O. E. (1985). The connections between the basolateral and central amygdaloid nuclei. Neuroscience letters, 56, 307-309.

85.

Sugita, S., & North, R. A. (1993). Opioid actions on neurons of rat lateral amygdala in vitro. Brain Research, 612, 151-155.

86.

Tempel, A., & Zukin, R. S. (1987). Neuroanatomical patterns of the mu, delta, and kappa opioid receptors of rat brain as determined by quantitative in vitro autoradiography. Proceedings of the National Academy of Sciences, 84, 4308-4312.

87.

Tershiner, S. A., & Helmstetter, F. J. (2000). Antinociception produced by mu opioid receptor activation in the amygdala is partly dependent on activation of mu opioid and neurotensin receptors in the ventral periaqueductal gray. Brain Research, 865(1), 17-26.

88.

Walker, D. L., & Davis M. (1997). Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear. Journal of Neuroscience, 17, 9375-9383.

89.

Wang, C., Li, Q., Wilson, W. A. & Moore, S. D. (2001). Identification of physiological association between the lateral and central amygdala nuclei. Society for Neuroscience Abstracts, 27, 177.15.

90.

Young, R.F., & Chambi, I. (1987). Pain relief by electrical stimulation of the periaqueductal and periventricular gray matter. Journal of Neurosurgery, 66, 364-371.

91.

Young, W.S., & Kuhar, M.J. (1981). Neurotensin receptor localization by light microscopic autoradiography in rat brain. Brain Research, 206, 273-285.

한국심리학회지: 인지 및 생물