Mediators of Pain and Pain Processing

  • Mark N. Malinowski


Nociception is the reception and perception of pain, and it involves complex mechanisms. The mechanism(s) whereby the body detects, processes, and interprets pain and the biologically appropriate response involve a complex network of spinal and supraspinal structures. In response to pain, there is not only ascension of the signal but descending mechanisms that lead to both adaptive and potentially maladaptive effects. Mechanisms that lead to continued pain or its resolution are dependent not only on the roles of the anatomical structures themselves but also on the neural transmitters and vast array of receptors and second messenger systems. Intensity and duration of nociceptive stimuli play a key role in the processing and response to pain. Cognitive and emotional responses are affected and may influence subconscious processing under both normal and pathological states.


Nociception Ascending pathways Descending pathways Excitatory amino acids Facilitation Inhibition Synaptic plasticity Dorsal horns Lamina Neuromatrix 

Recommended Reading

  1. 1.
    Gebhart G. Descending modulation of pain. Neurosci Biobehav Rev. 2004;27:729–37.CrossRefGoogle Scholar
  2. 2.
    Heinricher M, Tavares I, Leith J, Lumb B. Descending control of nociception: specificity, recruitment and plasticity. Brain Res Rev. 2009;60:214–25.CrossRefGoogle Scholar
  3. 3.
    Kandel E, Schwartz J, Jessell J, Siegelbaum S, Hudspeth A. Principles of neural science. 5th ed. New York: The McGraw-Hill Companies; 2013. p. 449–555.Google Scholar
  4. 4.
    Lau B, Vaughan C. Descending modulation of pain: the GABA disinhibition hypothesis of analgesia. Curr Opin Neurobiol. 2014;29:159–64.CrossRefGoogle Scholar
  5. 5.
    Llorca-Torralba M, Borges G, Neto F, Mico J, Berrocoso E. Noradrenergic locus coeruleus pathways in pain modulation. Neuroscience. 2016;338:93–113.CrossRefGoogle Scholar
  6. 6.
    Martins I, Tavares I. Reticular formation and pain: the past and future. Front Neuroanat. 2017;11(51):1–14.Google Scholar
  7. 7.
    Millan M. The induction of pain: an integrative review. Prog Neurobiol. 1999;57:1–164.CrossRefGoogle Scholar
  8. 8.
    Millan M. Descending control of pain. Prog Neurobiol. 2002;66:355–474.CrossRefGoogle Scholar
  9. 9.
    Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol. 2006;80:53–83.CrossRefGoogle Scholar
  10. 10.
    Pertovaara A. The noradrenergic pain regulation system: a potential target for pain therapy. Eur J Pharm. 2013;716:2–7.CrossRefGoogle Scholar
  11. 11.
    Rainville P. Brain mechanisms of pain affect and pain modulation. Curr Opp Neurobiol. 2002;12:195–204.CrossRefGoogle Scholar
  12. 12.
    Steeds C. The anatomy and physiology of pain. Surgery. 2013;31(2):49–53.Google Scholar
  13. 13.
    Taylor B, Westlund K. The noradrenergic locus coeruleus as a chronic pain generator. J Neurosci Res. 2017;95:1336–46.CrossRefGoogle Scholar
  14. 14.
    Vanegas H, Schaible H. Descending control of persistent pain: inhibitory or facilitatory? Brain Res Rev. 2004;46:295–309.CrossRefGoogle Scholar
  15. 15.
    Viguier F, Michot B, Hamon M, Bourgoin S. Multiple roles of serotonin in pain control mechanisms – implications of the 5-HT7 and other 5-HT receptor subtypes. Eur J Pharm. 2013;716:8–16.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Mark N. Malinowski
    • 1
  1. 1.Adena Spine CenterChillicotheUSA

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