Skip to main content
SpringerLink
Log in
Book cover

Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches pp 3–21Cite as

A Survey of Systems Involved in Nociceptive Processing

  • Chapter
  • First Online:

Abstract

High-intensity afferent input, tissue injury and inflammation, and injury to the peripheral nerve will initiate pain states with characteristic psychophysical properties. As will be considered below, this information processing can be modified to change the content of the message generated by a given stimulus to enhance the pain state (e.g., produce hyperalgesia), normalize a hyperalgesic state, or produce a decrease in pain sensitivity (e.g., produce analgesia). Management of that pain state is addressed by the use of agents or interventions which though specific targets at the level of the sensory afferent, the spinal dorsal horn or at higher-order levels (supraspinal) modify the contents of the sensory message generated by that physical stimulus. The important advances in the development of pain therapeutics have reflected upon the role played by specific underlying mechanisms which regulate these events.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Dougherty PM. Central sensitization and cutaneous hyperalgesia. Semin Pain Med. 2003;1:121–31.

    Article  Google Scholar 

  2. Johanek L, Shim B, Meyer RA. Chapter 4 Primary hyperalgesia and nociceptor sensitization. Handb Clin Neurol. 2006;81:35–47.

    Article  PubMed  Google Scholar 

  3. Mayer EA, Gebhart GF. Basic and clinical aspects of visceral hyperalgesia. Gastroenterology. 1994;107:271–93.

    PubMed  CAS  Google Scholar 

  4. Baron R. Neuropathic pain: a clinical perspective. Handb Exp Pharmacol. 2009;194:3–30.

    Article  PubMed  CAS  Google Scholar 

  5. Stucky CL, Dubin AE, Jeske NA, Malin SA, McKemy DD, Story GM. Roles of transient receptor potential channels in pain. Brain Res Rev. 2009;60:2–23.

    Article  PubMed  CAS  Google Scholar 

  6. Binshtok AM. Mechanisms of nociceptive transduction and transmission: a machinery for pain sensation and tools for selective analgesia. Int Rev Neurobiol. 2011;97:143–77.

    Article  PubMed  CAS  Google Scholar 

  7. Cortright DN, Szallasi A. TRP channels and pain. Curr Pharm Des. 2009;15(15):1736–49.

    Article  PubMed  CAS  Google Scholar 

  8. Dib-Hajj SD, Black JA, Waxman SG. Voltage-gated sodium channels: therapeutic targets for pain. Pain Med. 2009;10(7):1260–9.

    Article  PubMed  Google Scholar 

  9. Cohen CJ. Targeting voltage-gated sodium channels for treating neuropathic and inflammatory pain. Curr Pharm Biotechnol. 2011;12:1715–9.

    Article  PubMed  CAS  Google Scholar 

  10. Raja SN, Meyer RA, Campbell JN. Peripheral mechanisms of somatic pain. Anesthesiology. 1988;68:571–90.

    Article  PubMed  CAS  Google Scholar 

  11. Yaksh TL. Calcium channels as therapeutic targets in neuropathic pain. J Pain. 2006;7(1 Suppl 1):S13–30.

    PubMed  CAS  Google Scholar 

  12. Ruscheweyh R, Forsthuber L, Schoffnegger D, Sandkühler J. Modification of classical neurochemical markers in identified primary afferent neurons with abeta-, adelta-, and C-fibers after chronic constriction injury in mice. J Comp Neurol. 2007;502:325–36.

    Article  PubMed  CAS  Google Scholar 

  13. Willis Jr WD. The somatosensory system, with emphasis on structures important for pain. Brain Res Rev. 2007;55:297–313.

    Article  PubMed  Google Scholar 

  14. Todd AJ, Spike RC. The localization of classical transmitters and neuropeptides within neurons in laminae I-III of the mammalian spinal dorsal horn. Prog Neurobiol. 1993;41:609–45.

    Article  PubMed  CAS  Google Scholar 

  15. Todd AJ. Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci. 2010;11:823–36.

    Article  PubMed  CAS  Google Scholar 

  16. Ralston 3rd HJ. Pain and the primate thalamus. Prog Brain Res. 2005;149:1–10.

    Article  PubMed  Google Scholar 

  17. Reichling DB, Levine JD. Critical role of nociceptor plasticity in chronic pain. Trends Neurosci. 2009;32:611–8.

    Article  PubMed  CAS  Google Scholar 

  18. Herrero JF, Laird JM, López-García JA. Wind-up of spinal cord neurones and pain sensation: much ado about something? Prog Neurobiol. 2000;61:169–203.

    Article  PubMed  CAS  Google Scholar 

  19. Dickenson AH, Chapman V, Green GM. The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord. Gen Pharmacol. 1997;28:633–8.

    Article  PubMed  CAS  Google Scholar 

  20. Bleakman D, Alt A, Nisenbaum ES. Glutamate receptors and pain. Semin Cell Dev Biol. 2006;17:592–604.

    Article  PubMed  CAS  Google Scholar 

  21. Luo C, Seeburg PH, Sprengel R, Kuner R. Activity-dependent potentiation of calcium signals in spinal sensory networks in inflammatory pain states. Pain. 2008;140:358–67.

    Article  PubMed  CAS  Google Scholar 

  22. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10:895–926.

    Article  PubMed  Google Scholar 

  23. Ji RR, Kawasaki Y, Zhuang ZY, Wen YR, Zhang YQ. Protein kinases as potential targets for the treatment of pathological pain. Handb Exp Pharmacol. 2007;177:359–89.

    Article  PubMed  CAS  Google Scholar 

  24. Velázquez KT, Mohammad H, Sweitzer SM. Protein kinase C in pain: involvement of multiple isoforms. Pharmacol Res. 2007;55:578–89.

    Article  PubMed  Google Scholar 

  25. Svensson CI, Yaksh TL. The spinal phospholipase-cyclooxygenase-prostanoid cascade in nociceptive processing. Annu Rev Pharmacol Toxicol. 2002;42:553–83.

    Article  PubMed  CAS  Google Scholar 

  26. Zeilhofer HU. The glycinergic control of spinal pain processing. Cell Mol Life Sci. 2005;62:2027–35.

    Article  PubMed  CAS  Google Scholar 

  27. Tang Q, Svensson CI, Fitzsimmons B, Webb M, Yaksh TL, Hua XY. Inhibition of spinal constitutive NOS-2 by 1400 W attenuates tissue injury and inflammation-induced hyperalgesia and spinal p38 activation. Eur J Neurosci. 2007;25:2964–72.

    Article  PubMed  Google Scholar 

  28. Suzuki R, Rygh LJ, Dickenson AH. Bad news from the brain: descending 5-HT pathways that control spinal pain processing. Trends Pharmacol Sci. 2004;25:613–7.

    Article  PubMed  CAS  Google Scholar 

  29. Milligan ED, Watkins LR. Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci. 2009;10:23–36.

    Article  PubMed  CAS  Google Scholar 

  30. Ren K, Dubner R. Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol. 2008;21:570–9.

    Article  PubMed  Google Scholar 

  31. Abbadie C, Bhangoo S, De Koninck Y, Malcangio M, Melik-Parsadaniantz S, White FA. Chemokines and pain mechanisms. Brain Res Rev. 2009;60:125–34.

    Article  PubMed  CAS  Google Scholar 

  32. Clark AK, Staniland AA, Malcangio M. Fractalkine/CX3CR1 signalling in chronic pain and inflammation. Curr Pharm Biotechnol. 2011;12:1707–14.

    Article  PubMed  CAS  Google Scholar 

  33. Grace PM, Rolan PE, Hutchinson MR. Peripheral immune contributions to the maintenance of central glial activation underlying neuropathic pain. Brain Behav Immun. 2011;25:1322–32.

    Article  PubMed  CAS  Google Scholar 

  34. Ledeboer A, Sloane EM, Milligan ED, Frank MG, Mahony JH, Maier SF, Watkins LR. Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain. 2005;115:71–83.

    Article  PubMed  CAS  Google Scholar 

  35. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006;367:1618–25.

    Article  PubMed  Google Scholar 

  36. Xu Q, Yaksh TL. A brief comparison of the pathophysiology of inflammatory versus neuropathic pain. Curr Opin Anaesthesiol. 2011;24:400–7.

    Article  PubMed  Google Scholar 

  37. Tuchman M, Barrett JA, Donevan S, Hedberg TG, Taylor CP. Central sensitization and Ca(V) α2δ ligands in chronic pain syndromes: pathologic processes and pharmacologic effect. J Pain. 2010;12:1241–9.

    Google Scholar 

  38. Bráz JM, Ackerman L, Basbaum AI. Sciatic nerve transection triggers release and intercellular transfer of a genetically expressed macromolecular tracer in dorsal root ganglia. J Comp Neurol. 2011;519:2648–57.

    Article  PubMed  Google Scholar 

  39. Zimmermann M. Pathobiology of neuropathic pain. Eur J Pharmacol. 2001;429:23–37.

    Article  PubMed  CAS  Google Scholar 

  40. Takeda M, Tsuboi Y, Kitagawa J, Nakagawa K, Iwata K, Matsumoto S. Potassium channels as a potential therapeutic target for trigeminal neuropathic and inflammatory pain. Mol Pain. 2011;7:5.

    Article  PubMed  Google Scholar 

  41. Devor M, Wall PD. Cross-excitation in dorsal root ganglia of nerve-injured and intact rats. J Neurophysiol. 1990;64(6):1733–46.

    PubMed  CAS  Google Scholar 

  42. Yaksh TL. Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists. Pain. 1989;37:111–23.

    Article  PubMed  CAS  Google Scholar 

  43. Sivilotti L, Woolf CJ. The contribution of GABAA and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord. J Neurophysiol. 1994;72:169–79.

    PubMed  CAS  Google Scholar 

  44. Polgár E, Hughes DI, Riddell JS, Maxwell DJ, Puskár Z, Todd AJ. Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain. Pain. 2003;104:229–39.

    Article  PubMed  Google Scholar 

  45. Price TJ, Cervero F, de Koninck Y. Role of cation-chloride-cotransporters (CCC) in pain and hyperalgesia. Curr Top Med Chem. 2005;5(6):547–55.

    Article  PubMed  CAS  Google Scholar 

  46. Cao H, Zhang YQ. Spinal glial activation contributes to pathological pain states. Neurosci Biobehav Rev. 2008;32(5):972–83.

    Article  PubMed  Google Scholar 

  47. McLachlan EM, Jänig W, Devor M, Michaelis M. Peripheral nerve injury triggers noradrenergic sprouting within dorsal-root ganglia. Nature. 1993;363:543–6.

    Article  PubMed  CAS  Google Scholar 

  48. Drummond PD. Involvement of the sympathetic nervous system in complex regional pain syndrome. Int J Low Extrem Wounds. 2004;3:35–42.

    Article  PubMed  Google Scholar 

  49. Borsook D, Becerra L. CNS animal fMRI in pain and analgesia. Neurosci Biobehav Rev. 2011;35:1125–43.

    Article  PubMed  Google Scholar 

  50. D’Souza WN, Ng GY, Youngblood BD, Tsuji W, Lehto SG. A review of current animal models of osteoarthritis pain. Curr Pharm Biotechnol. 2011;12:1596–612.

    Article  PubMed  Google Scholar 

  51. Mogil JS. Animal models of pain: progress and challenges. Nat Rev Neurosci. 2009;10:283–94.

    Article  PubMed  CAS  Google Scholar 

  52. Waszkielewicz AM, Gunia A, Słoczyńska K, Marona H. Evaluation of anticonvulsants for possible use in neuropathic pain. Curr Med Chem. 2011;18:4344–58.

    Article  PubMed  CAS  Google Scholar 

  53. Xu J, Brennan TJ. The pathophysiology of acute pain: animal models. Curr Opin Anaesthesiol. 2011;24:508–14.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Anesthesia Research Lab 0818, UC San Diego, 9500 Gilman Dr (CTF-312), La Jolla, CA, 92093, USA

    Tony L. Yaksh Ph.D.

  2. University of California, San Diego School of Medicine, La Jolla, CA, USA

    Tony L. Yaksh Ph.D.

  3. Anesthesia Research Lab 0818, UC San Diego, 9500 Gilman Dr (CTF-312), La Jolla, CA, 92093, USA

    Ashley J. Wiese DVM, MS, DACVA

  4. Department of Anesthesiology, University of California, San Diego Medical Center, La Jolla, CA, USA

    Ashley J. Wiese DVM, MS, DACVA

Authors
  1. Tony L. Yaksh Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ashley J. Wiese DVM, MS, DACVA
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tony L. Yaksh Ph.D. .

Editor information

Editors and Affiliations

  1. The Center for Pain Relief, Inc., West Virginia University, 400 Court Street, Suite 100, Charleston, 25301, West Virginia, USA

    Timothy R. Deer

  2. Stanford Pain Management Center, Redwood City, CA, Clinic Chief, Stanford University School of Medicine, Stanford, 94065, California, USA

    Michael S. Leong

  3. Department of Anesthesiology, Rush Medical College, Professor, Rush University Medical Center, Chicago, 60612, Illinois, USA

    Asokumar Buvanendran

  4. Pennsylvania State University, College of Medicine, Department of Anesthesiology, Milton S. Hershey Medical Center, Hershey, 17033-0850, Pennsylvania, USA

    Vitaly Gordin

  5. Center for Interventional Pain and Spine, Newark, DE USA, Medical Director, Bryn Mawr Hospital, Bryn Mawr, 19010, Pennsylvania, USA

    Philip S. Kim

  6. President, National Institute of Pain, Tampa, 33558, Florida, USA

    Sunil J. Panchal

  7. The LITE Center, Clinical Associate Professor, Medical Director, School of Medicine, Miami, 33143, Florida, USA

    Albert L. Ray

Rights and permissions

Reprints and permissions

Copyright information

© 2013 American Academy of Pain Medicine

About this chapter

Cite this chapter

Yaksh, T.L., Wiese, A.J. (2013). A Survey of Systems Involved in Nociceptive Processing. In: Deer, T., et al. Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1560-2_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-1560-2_1

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-1559-6

  • Online ISBN: 978-1-4614-1560-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation