Skip to main content
SpringerLink
Log in

Endogenous Biphasic Modulation

  • Chapter
Molecular Pain

  • 1050 Accesses

Abstract

It is well documented that sensory transmission, including pain, is subject to endogenous inhibitory influences at the dorsal horn of the spinal cord. Recent results, from behavioral to molecular studies, demonstrate that endogenous modulatory systems are bi-phasic, including inhibitory and new facilitatory systems. In this review, we propose the existence of endogenous facilitatory systems in the brain, and review evidence supporting the hypothesis. We believe that understanding the molecular and cellular basis of endogenous facilitatory systems hold the hope for better fixture treatment of patients with chronic pain.

The introduction of Dr. Zhuo, please refer to Chapter 8.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

General Citations

  • Fields H. 2004. State-dependent opioid control of pain. Nat Rev Neurosci, 5:565–575.

    Article  PubMed  CAS  Google Scholar 

  • Fields HL, Heinricher MM and Mason P. 1991. Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci, 7:309–338.

    Google Scholar 

  • Gebhart GF. 2004. Descending modulation of pain. Neurosci Biobehav Rev, 27:729–737.

    Article  PubMed  CAS  Google Scholar 

  • Mason P. 2005. Deconstructing endogenous pain modulation. J Neurophysiol, 94: 1659–1663.

    Article  PubMed  CAS  Google Scholar 

  • Mason P 1999. Central mechanisms of pain modulation. Curt Opin Neurobiol, 9: 436–441.

    Article  CAS  Google Scholar 

  • Millan MJ. 1999. The induction of pain: an integrative review. Progress in Neurobiology, 57:1–164.

    Article  PubMed  CAS  Google Scholar 

  • Porreca F, Ossipov MH, Gebhart GF. 2002. Chronic pain and medullary descending facilitation. Trends Neurosci, 25: 319–325.

    Article  PubMed  CAS  Google Scholar 

  • Robinson DA, Calejesan AA, Wei F, Gebhart GF, Zhuo M. 2004. Endogenous facilitation: from molecular mechanisms to persistent pain. Curr Neurovasc Res, 1: 11–20.

    Article  PubMed  CAS  Google Scholar 

  • Sandkuhler J. 1996. The organization and function of endogenous antinociceptive systems. Prog Neurobiol, 50:49–81.

    PubMed  CAS  Google Scholar 

  • Urban MO, Gebhart GF. 1999. Supraspinal contributions to hyperalgesia. PNAS, 96:7687–7692.

    Article  PubMed  CAS  Google Scholar 

  • Zhuo M. 2000. Silent glutamatergic synapses and long-term facilitation in spinal dorsal horn neurons. Progress in Brain Research, 129:101–113.

    Article  PubMed  CAS  Google Scholar 

  • Zhuo M. 2002. Glutamate receptors and persistent pain: targeting forebrain NR2B subunits. Drug Discov Today, 7:259–267.

    Article  PubMed  CAS  Google Scholar 

Discovery Findings

  • Almeida A, Storkson R, Lima D, Hole K, Tjolsen A. 1999. The medullary dorsal reticular nucleus facilitates pain behaviour induced by formalin in the rat. Eur J Neurosci, 11:110–122.

    Article  PubMed  CAS  Google Scholar 

  • Calejesan AA, Kim SJ, Zhuo M. 2000. Descending facilitatory modulation of a behavioral nociceptive response by stimulation in the adult rat anterior cingulate cortex. Eur J Pain, 4:83–96.

    Article  PubMed  CAS  Google Scholar 

  • Donovan-Rodriguez T, Urch CE, Dickenson AH. 2005. Evidence of a role for descending serotonergic facilitation in a rat model of cancer-induced bone pain. Neurosci Lett, 393:237–242.

    Article  PubMed  Google Scholar 

  • Gardell LR, Vanderah TW, Gardell SE, Wang R, Ossipov MH, Lai J, Porreca F. 2003. Enhanced evoked excitatory transmitter release in experimental neuropathy requires descending facilitation. J Neurosci, 23:8370–8379.

    PubMed  CAS  Google Scholar 

  • Hori Y, Endo K and Takahashi T. 1996. Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of the rat spinal cord. J Physiol (Lond), 492:867–876.

    CAS  Google Scholar 

  • Johansen JP, Fields HL, Manning BH. 2001. The affective component of pain in rodents: direct evidence for a contribution of the anterior cingulate cortex. PNAS, 98:8077–8082.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan H, Fields HL. 1991. Hyperalgesia during acute opioid abstinence: evidence for a nociceptive facilitating function of the rostral ventromedial medulla. J Neurosci, 11:1433–1439.

    PubMed  CAS  Google Scholar 

  • Lima D, Almeida A. 2002. The medullary dorsal reticular nucleus as a pronociceptive centre of the pain control system. Prog Neurobiol, 66:81–108.

    Article  PubMed  Google Scholar 

  • Lopez-Garcia JA and King AE. 1996. Pre-and post-synaptic actions of 5-hydroxytryptamine in the rat lumbar dorsal horn in vitro: implications for somatosensory transmission. Eur J Neurosci, 8:2188–2197.

    Article  PubMed  CAS  Google Scholar 

  • Meng ID, Manning BH, Martin WJ, Fields HL. 1998. An analgesia circuit activated by cannabinoids. Nature, 395:381–383.

    Article  PubMed  CAS  Google Scholar 

  • Morgan MM, Fields HL. 1994. Pronounced changes in the activity of nociceptive modulatory neurons in the rostral ventromedial medulla in response to prolonged thermal noxious stimuli. J Neurophysiol, 72:1161–1170.

    PubMed  CAS  Google Scholar 

  • Neugebauer V, Schaible HG. 1990. Evidence for a central component in the sensitization of spinal neurons with joint input during development of acute arthritis in cat’s knee. J Neurophysiol, 64:299–311.

    PubMed  CAS  Google Scholar 

  • Pan ZZ, Tershner SA, Fields HL. 1997. Cellular mechanism for anti-analgesic action of agonists of the kappa-opioid receptor. Nature, 389:382–385.

    Article  PubMed  CAS  Google Scholar 

  • Robinson DA, Calejesan AA and Zhuo M. 2002. Long-lasting changes in rostral ventral medulla neuronal activity following inflammation in the adult rat. Journal of Pain, 3:292–300.

    Article  PubMed  Google Scholar 

  • Sikes RW and Vogt BA. 1992. Nociceptive neurons in area 24 of rabbit cingulate cortex. Journal of Neurophysiology, 68:1720–1732.

    PubMed  CAS  Google Scholar 

  • Suzuki R, Rahman W, Hunt SP, Dickenson AH. 2004. Descending facilitatory control of mechanically evoked responses is enhanced in deep dorsal horn neurones following peripheral nerve injury. Brain Res, 1019:68–76.

    Article  PubMed  CAS  Google Scholar 

  • Talbot JD, Marrett S, Evans AC, Meyer E, Bushnell MC and Duncan GH. 1991. Multiple representations of pain in human cerebral cortex. Science, 251:1355–1358.

    Article  PubMed  CAS  Google Scholar 

  • Tang YP, Xhimizu E, Dube GR, Rampon C, Kerchner GA, Zhuo M, Liu G and Tsien JZ. 1999. Genetic enhancement of learning and memory in mice. Nature, 401:63–69.

    Article  PubMed  CAS  Google Scholar 

  • Thomas DA, McGowan MK, Hammond DL. 1995. Microinjection of baclofen in the ventromedial medulla of rats: antinociception at low doses and hyperalgesia at high doses. J Pharmacol Exp Ther, 275: 274–284.

    PubMed  CAS  Google Scholar 

  • Urban MO, Gebhart GF. 1999. Supraspinal contributions to hyperalgesia. Proc Natl Acad Sci USA, 96:7687–7692.

    Article  PubMed  CAS  Google Scholar 

  • Urban MO, Jiang MC, Gebhart GF. 1996. Participation of central descending nociceptive facilitatory systems in secondary hyperalgesia produced by mustard oil. Brain Res, 737:83–91.

    Article  PubMed  CAS  Google Scholar 

  • Vanegas H, Schaible HG. 2004. Descending control of persistent pain: inhibitory or facilitatory? Brain Res Brain Res Rev, 46:295–309.

    Article  PubMed  Google Scholar 

  • Wang GD and Zhuo M. 2002. Synergistic enhancement of glutamate-mediated responses by serotonin and forskolin in adult mouse spinal dorsal horn neurons. J Neurophysiology, 87:732–739.

    CAS  Google Scholar 

  • Wei F and Zhuo M. 2001. Potentiation of synaptic responses in the anterior cingulate cortex following digital amputation in rat. J Physiology (Lond), 532:823–833.

    Article  CAS  Google Scholar 

  • Wei F, Li P and Zhuo M. 1999. Loss of synaptic depression in mammalian anterior cingulate cortex after amputation. J of Neuroscience, 19:9346–9354.

    CAS  Google Scholar 

  • Wei F, Wang GD, Kerchner GA, Kim SJ, Xu HM, Chen ZF. and Zhuo M. 2001. Genetic enhancement of inflammatory pain by forebrain NR2B overexpression. Nature Neuroscience, 4:164–169.

    Article  PubMed  CAS  Google Scholar 

  • Wei F, Qiu CS, Kim SJ, Muglia L, Maas JW, Pineda W, Xu HM, Chen ZF, Storm DR, Muglia LJ and Zhuo M. 2002. Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases. Neuron, 36:713–726.

    Article  PubMed  CAS  Google Scholar 

  • Wei F, Dubner R, Ren K. 1999. Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation. Pain, 80:127–141.

    Article  PubMed  CAS  Google Scholar 

  • Xie JY, Herman DS, Stiller CO, Gardell LR, Ossipov MH, Lai J, Porreca F, Vanderah TW. 2005. Cholecystokinin in the rostral ventromedial medulla mediates opioid-induced hyperalgesia and antinociceptive tolerance. J Neurosci, 25:409–416.

    Article  PubMed  Google Scholar 

  • Zhang L, Zhang Y, Zhao ZQ. 2005. Anterior cingulate cortex contributes to the descending facilitatory modulation of pain via dorsal reticular nucleus. Eur J Neurosci, 22: 1141–1148.

    Article  PubMed  Google Scholar 

  • Zhuo M and Gebhart GF. 1990a. Characterization of descending inhibition and facilitation from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. Pain, 42:337–350.

    Article  PubMed  CAS  Google Scholar 

  • Zhuo M and Gebhart GF. 1990b. Spinal cholinergic and monoaminergic receptors mediate descending inhibition from the nuclei reticularis gigantocellularis pars alpha in the rat. Brain Research, 535: 67–78.

    Article  PubMed  CAS  Google Scholar 

  • Zhuo M and Gebhart GF. 1991. Spinal serotonin receptors mediate descending facilitation pfs nociceptive reflex from the nuclei reticularis goigantocellularis and gigantocel-lularis pars alpha in the rat. Brain Research, 550:35–48.

    Article  PubMed  CAS  Google Scholar 

  • Zhuo M and Gebhart GF. 1992. Characterization of descending facilitation and inhibition of spinal nociceptive transmission from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. J Neurophysiol, 67:1599–1614.

    PubMed  CAS  Google Scholar 

  • Zhuo M and Gebhart GF. 1997. Biphasic modulation of spinal nociceptive transmission from the medullary raphe nuclei in the rat. J Neurophysiol, 78: 746–758.

    PubMed  CAS  Google Scholar 

  • Zhuo M and Gebhart GF. 2002a. Biphasic modulation of a visceral nociceptive reflex from the rostroventral medial medulla in the rat. Gastroenterology, 122:1007–1019.

    Article  PubMed  Google Scholar 

  • Zhuo M and Gebhart GF. 2002b. Modulation of noxious and non-noxious spinal mechanical transmission from the rostral medial medulla in the rat. J Neurophysiology, 88:2928–2941.

    Article  CAS  Google Scholar 

  • Zhuo M, Sengupta JN and Gebhart GF. 2002. Biphasic modulation of spinal visceral nociceptive transmission from the rostroventral medial medulla in the rat. J Neurophysiology, 87:2225–2236.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, University of Toronto, Medical Sciences Bldg, Rm 3342 1 King’s College Circle, Toronto, Ontario, M5S 1A8, Canada

    Min Zhuo Ph D (Canada Research Chair in Pain and Cognition, Tier I, EJLB-CIHR Michael Smith Chair in Neurosciences and Mental Health and Professor)

  2. Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Gerald F. Gebhart PhD (Professor and Director)

Authors
  1. Min Zhuo Ph D
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gerald F. Gebhart PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Physiology, University of Toronto, Medical Sciences Bldg, Rm 3342 1 King’s College Circle, Toronto, Ontario, Canada, M5S 1A8

    Min Zhuo

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Higher Education Press

About this chapter

Cite this chapter

Zhuo, M., Gebhart, G.F. (2007). Endogenous Biphasic Modulation. In: Zhuo, M. (eds) Molecular Pain. Springer, New York, NY. https://doi.org/10.1007/978-0-387-75269-3_27

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-75269-3_27

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-75268-6

  • Online ISBN: 978-0-387-75269-3

Publish with us

Policies and ethics

Search

Navigation