Skip to main content
SpringerLink
Log in

Neuroplasticity, Sensitization, and Pain

  • Chapter
  • First Online:
Treatment of Chronic Pain by Integrative Approaches

Abstract

Neuroplasticity is a term that is used quite frequently these days in pain-related literature, and in many ways, it has come to be a term especially associated with maldynia. However, neuroplasticity is a term that more accurately delineates the way our nervous system operates, peripherally and centrally, and it should have no intrinsic judgment placed upon it. It simply is what it is.

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

Access this chapter

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 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Institutional subscriptions

Similar content being viewed by others

References

  1. Lippe P. An apologia in defense of pain medicine. Clin J Pain. 1998;14:189–90.

    Article  CAS  PubMed  Google Scholar 

  2. AMA Council on Science and Public Health Report 5. Maldynia: pathophysiology and non-pharmacologic treatment. 2010.

    Google Scholar 

  3. Arden J. Rewire your brain. New York: Wiley; 2010.

    Google Scholar 

  4. Schwartz J, Begley S. The mind and the brain: neuroplasticity and the power of mental force. New York: Harper Collins; 2002.

    Google Scholar 

  5. Doidge N. The brain that changes itself. New York: Penguin Group; 2007.

    Google Scholar 

  6. Voscopoulos C, Lema M. When does acute pain become chronic? Br J Anaesth. 2010;105 Suppl 1:169–85.

    Google Scholar 

  7. Apkarian A, Bushnell M, Treede R-D, Zubieta J. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9:463–84.

    Article  PubMed  Google Scholar 

  8. Price D, Harkins S. The affective-motivational dimension of pain: a two-stage model. APS J. 1992;1:229–39.

    Article  Google Scholar 

  9. Reichling DB, Levine JD. Critical role of nociceptor plasticity in chronic pain. Trends Neurosci. 2009;32(12):611–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Descalzi G, Kim S, Zhuo M. Presynaptic and postsynaptic cortical mechanisms of chronic pain. Mol Neurobiol. 2009;40(3):253–9.

    Article  CAS  PubMed  Google Scholar 

  12. Treede RD. Highly localized inhibition of pain via long-term depression (LTD). Clin Neurophysiol. 2008;119(8):1703–4.

    Article  PubMed  Google Scholar 

  13. Hong CZ. New trends in myofascial pain syndrome. Zhonghua Yi Xue Za Zhi (Taipei). 2002;65(11):501–12.

    Google Scholar 

  14. Nielsen LA, Henriksson KG. Pathophysiological mechanisms in chronic musculoskeletal pain (fibromyalgia): the role of central and peripheral sensitization and pain disinhibition. Best Pract Res Clin Rheumatol. 2007;21(3):465–80.

    Article  PubMed  Google Scholar 

  15. Henrikssen KG. Hypersensitivity in muscle pain syndromes. Curr Pain Headache Rep. 2003;7(6):426–32.

    Article  Google Scholar 

  16. Bendtsen L, Fernández-de-la-Peñas C. The role of muscles in tension-type headache. Curr Pain Headache Rep. 2011;15(6):451–8.

    Article  PubMed  Google Scholar 

  17. Fernández-Lao C, Cantarero-Villanueva I, Fernández-de-la-Peñas C, et al. Myofascial trigger points in neck and shoulder muscles and widespread pressure pain hypersensitivity in patients with postmastectomy pain: evidence of peripheral and central sensitization. Clin J Pain. 2010;26(9):798–806.

    Article  PubMed  Google Scholar 

  18. Ge HY, Fernández-de-la-Peñas C, Yue SW. Myofascial trigger points: spontaneous electrical activity and its consequences for pain induction and propagation. Chin Med. 2011;6:3.

    Article  Google Scholar 

  19. Navarro X. Neural plasticity after nerve injury and regeneration. Int Rev Neurobiol. 2009;87:483–505.

    Article  PubMed  Google Scholar 

  20. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10(9):895–926.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Kuner R. Central mechanisms of pathological pain. Nat Med. 2010;16(11):1258–66.

    Article  CAS  PubMed  Google Scholar 

  22. Park J, Luo ZD. Calcium channel functions in pain processing. Channels (Austin). 2010;4(6):510–7.

    Article  CAS  Google Scholar 

  23. Tuchman M, Barrett JA, Donevan S, et al. Central sensitization and Ca(V)α2δ ligands in chronic pain syndromes: pathologic processes and pharmacologic effect. J Pain. 2010;11(12):1241–9.

    Article  CAS  PubMed  Google Scholar 

  24. Palazzo E, Luongo L, de Novellis V, et al. Moving towards supraspinal TRPV1 receptors for chronic pain relief. Mol Pain. 2010;6:66.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Alter BJ, Gereau RW. Hotheaded: TRPV1 as mediator of hippocampal synaptic plasticity. Neuron. 2008;57(5):629–31.

    Article  CAS  PubMed  Google Scholar 

  26. Adedoyin MO, Vicini S, Neale JH. Endogenous N-acetylaspartylglutamate (NAAG) inhibits synaptic plasticity/transmission in the amygdala in a mouse inflammatory pain model. Mol Pain. 2010;6:60.

    PubMed Central  PubMed  Google Scholar 

  27. Larsson M, Broman J. Synaptic plasticity and pain: role of ionotropic glutamate receptors. Neuroscientist. 2011;17(3):256–73. Epub 2010 Apr 1. Review.

    Article  CAS  PubMed  Google Scholar 

  28. Zhou HY, Chen SR, Chen H, Pan HL. Functional plasticity of group II metabotropic glutamate receptors in regulation spinal excitatory and inhibitory synaptic input in neuropathic pain. J Pharmacol Exp Ther. 2011;336(1):254–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Liu XJ, Salter MW. Glutamate receptor phosphorylation and trafficking in pain plasticity in spinal cord dorsal horn. Eur J Neurosci. 2010;32(2):278–89.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Sanderson JL, Dell’Acqua ML. AKAP signaling complexes in regulation of excitatory synaptic plasticity. Neuroscientist. 2011;17(3):321–36. Epub 2011 Apr 15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Li XY, Ko HG, Chen T, et al. Alleviating neuropathic pain hypersensitivity by inhibiting PKMzeta in the anterior cingulated cortex. Science. 2010;330(6009):1400–4.

    Article  CAS  PubMed  Google Scholar 

  32. Maneepak M, le Grand S, Srikiatkhachorn A. Serotonin depletion increases nociception-evoked trigeminal NMDA receptor phosphorylation. Headache. 2009;49(3):375–82.

    Article  PubMed  Google Scholar 

  33. Hald A. Spinal astrogliosis in pain models: cause and effects. Cell Mol Neurobiol. 2009;29(5):609–19.

    Article  CAS  PubMed  Google Scholar 

  34. Gwak YS, Hulsebosch CE. GABA and central neuropathic pain following spinal cord injury. Neuropharmacology. 2011;60(5):799–808.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Peng B, Lin JY, Shang Y, et al. Plasticity in the synaptic number associated with neuropathic pain in the rat spinal dorsal horn: a stereological study. Neurosci Lett. 2010;486(1):24–8.

    Article  CAS  PubMed  Google Scholar 

  36. Hjornevik T, Schoultz BW, Marton J, et al. Spinal long-term potentiation is associated with reduced opioid neurotransmission in the rat brain. Clin Physiol Funct Imaging. 2010;30(4):285–93.

    Article  CAS  PubMed  Google Scholar 

  37. Blanchard J, Chohan MO, Li B, et al. Beneficial effect of a CNTF tetrapeptide on adult hippocampal neurogenesis, neuronal plasticity, and spatial memory in mice. J Alzheimers Dis. 2010;21(4):1185–95.

    CAS  PubMed  Google Scholar 

  38. Zhuo M. A synaptic model for pain: long-term potentiation in the anterior cingulate cortex. Mol Cells. 2007;23(3):259–71. Review.

    CAS  PubMed  Google Scholar 

  39. Zhao XY, Liu MG, Yuan DL, et al. Nociception-induced spatial and temporal plasticity of synaptic connection and function in the hippocampal formation of rats: a multi-electrode array recording. Mol Pain. 2009;5:55.

    Article  PubMed Central  PubMed  Google Scholar 

  40. Zhang L, Zhao ZQ. Plasticity changes of neuronal activities on central lateral nucleus by stimulation of the anterior cingulate cortex in rat. Brain Res Bull. 2010;81(6):574–8.

    Article  PubMed  Google Scholar 

  41. Maihöfner C. Neuropathic pain and neuroplasticity in functional imaging studies. Schmerz. 2010;24(2):137–45.

    Article  PubMed  Google Scholar 

  42. Teutsch S, Herken W, Bingel U, et al. Changes in brain gray matter due to repetitive painful stimulation. Neuroimage. 2008;42(2):845–9.

    Article  CAS  PubMed  Google Scholar 

  43. May A. Chronic pain may change the structure of the brain. Pain. 2008;137(1):7–15.

    Article  PubMed  Google Scholar 

  44. Ray A, Zbik A. Cognitive therapies and beyond. In: Tollison CD, editor. Practical pain management. 3rd ed. Philadelphia: Lippincott Williams and Wilkins; 2002. p. 189–208.

    Google Scholar 

  45. Gustin SM, Wrigley PJ, Siddall PJ, Henderson LA. Brain anatomy changes associated with persistent neuropathic pain following spinal cord injury. Cereb Cortex. 2010;20(6):1409–19.

    Article  CAS  PubMed  Google Scholar 

  46. Neugebauer V, Galhardo V, Maione S, Mackey SC. Forebrain pain mechanisms. Brain Res Rev. 2009;60(1):226–42.

    Article  PubMed Central  PubMed  Google Scholar 

  47. Ji G, Sun H, Fu Y, et al. Cognitive impairment in pain through amygdala-driven prefrontal cortical deactivation. J Neurosci. 2010;30(15):5451–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Lovick TA, Devall AJ. Progesterone withdrawal-evoked plasticity of neural function in the female periaqueductal grey matter. Neural Plast. 2009;2009. doi:10.1155/2009/730902;730902. Epub 2008 Dec 2. Review.

  49. Rome H, Rome J. Limbically augmented pain syndrome (LAPS): kindling, corticolimbic sensitization, and convergence of affective and sensory symptoms in chronic pain disorders. Pain Med. 2000;1(1):7–23.

    Article  PubMed  Google Scholar 

  50. Staud R, Spaeth M. Psychophysical and neurochemical abnormalities of pain processing in fibromyalgia. CNS Spectr. 2008;13(3 Suppl):12–7.

    PubMed  Google Scholar 

  51. Schmidt-Wilcke T, Luerding R, Weigand T, et al. Striatal grey matter increase in patients suffering from fibromyalgia- – a voxel-based morphometry study. Pain. 2007;132 Suppl 1:s109–16.

    Article  PubMed  Google Scholar 

  52. Haas L, Portela LV, Böhmer AE, et al. Increased plasma levels of brain derived neurotrophic factor (BDNF) in patients with fibromyalgia. Neurochem Res. 2010;35(5):830–4.

    Article  CAS  PubMed  Google Scholar 

  53. Cuadros J, Vargas M. A new mind-body approach for a total healing of fibromyalgia: a case report. Am J Clin Hypn. 2009;52(1):3–12.

    Article  PubMed  Google Scholar 

  54. Morris LD, Grimmer-Somers KA, Spottiswoode B, Louw QA. Virtual reality exposure therapy as a treatment for pain catastrophizing in fibromyalgia patients: proof-of-concept study (study protocol). BMC Musculoskelet Disord. 2011;12(1):85.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Sañudo B, Galliano D, Carrasco L, et al. Effects of prolonged exercise program on key health outcomes in women with fibromyalgia: a randomized controlled trial. J Rehabil Med. 2011;43(6):521–6.

    Article  PubMed  Google Scholar 

  56. Arcos-Carmona IM, Castro-Sánchez AM, Matarán-Peñarrocha GA, Gutiérrez-Rubio AB, Ramos-González E, Moreno-Lorenzo C. Effects of aerobic exercise program and relaxation techniques on anxiety, quality of sleep, depression, and quality of life in patients with fibromyalgia: a randomized controlled trial. Med Clin (Barc). 2011;137(9):398–401. doi:10.1016/j.medcli.2010.09.045.Epub 2011 Feb 22 [Article in Spanish].

  57. Fontaine KR, Conn L, Clauw DJ. Effects of lifestyle physical activity in adults with fibromyalgia: results at follow-up. J Clin Rheumatol. 2011;17(2):64–8.

    Article  PubMed Central  PubMed  Google Scholar 

  58. Weeks SR, Anderson-Barnes VC, Tsao JW. Phantom limb pain: theories and therapies. Neurologist. 2010;16(5):277–86.

    Article  PubMed  Google Scholar 

  59. Flor H. Maladaptive plasticity, memory for pain and phantom limb pain: review and suggestions for new therapies. Expert Rev Neurother. 2008;8(5):809–18.

    Article  PubMed  Google Scholar 

  60. Sumitani M, Miyauchi S, Uematsu H, et al. Phantom limb pain originates from dysfunction of the primary motor cortex. Masui. 2010;59(11):1364–9.

    PubMed  Google Scholar 

  61. MacIver K, Lloyd DM, Kelly S, et al. Phantom limb pain, cortical reorganization and the therapeutic effect of mental imagery. Brain. 2008;131(Pt 8):2181–91.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Shapiro F. Eye movement desensitization and reprocessing. New York: Guilford; 1995.

    Google Scholar 

  63. Schneider J, Hofmann A, Rost C, Shapiro F. EMDR in the treatment of chronic phantom limb pain. Pain Med. 2008;9(1):76–82.

    Article  PubMed  Google Scholar 

  64. Nickel FT, Maihöfner C. Current concepts in pathophysiology of CRPS I. Handchir Mikrochir Plast Chir. 2010;42(1):8–14.

    Article  CAS  PubMed  Google Scholar 

  65. Bie B, Brown DL, Naguib M. Increased synaptic Glur1 subunits in the anterior cingulated cortex of rats with peripheral inflammation. Eur J Pharmacol. 2011;653(1–3):26–31.

    CAS  PubMed  Google Scholar 

  66. Christianson JA, Bielefeldt K, Altier C, et al. Development, plasticity and modulations of visceral afferents. Brain Res Rev. 2009;60(1):171–86.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Ceyhan GO, Demir IE, Maak M, Friess H. Fate of nerves in chronic pancreatitis: neural remodeling and pancreatic neuropathy. Best Pract Res Clin Gastroenterol. 2010;24(3):311–22.

    Article  PubMed  Google Scholar 

  68. Demir IE, Tieftrunk E, Maak M, et al. Pain mechanisms in chronic pancreatitis: of a master and his fire. Langenbecks Arch Surg. 2011;396(2):151–60.

    Article  PubMed Central  PubMed  Google Scholar 

  69. Silberstein S, et al. Neuropsychiatric aspects of primary headache disorders. In: Yudofsky S, Hales R, editors. Textbook of neuropsychiatry. 3rd ed. Washington DC: Amer Psychiatric Press; 1997. p. 381–412.

    Google Scholar 

  70. Tajti J, Vécsei L. The mechanism of peripheral and central sensitization in migraine. A literature revie. Neuropsychopharmacol Hung. 2009;11(1):15–21.

    PubMed  Google Scholar 

  71. Obermann M, Nebel K, Schumann C, et al. Gray matter changes related to chronic posttraumatic headache. Neurology. 2009;73(12):978–83.

    Article  PubMed  Google Scholar 

  72. Nau C. Pathophysiology of chronic postoperative pain. Anasthesiol Intensivmed Notfallmed Schmerzther. 2010;45(7–8):480–6.

    Article  PubMed  Google Scholar 

  73. Schnabel A, Pogatzki-Zahn E. Predictors of chronic pain following surgery. What do we know? Schmerz. 2010;24(5):517–31.

    Article  CAS  PubMed  Google Scholar 

  74. Chauvin M. Chronic pain after surgery. Presse Med. 2009;38(11):1613–20.

    Article  PubMed  Google Scholar 

  75. Berger JV, Knaepen L, Janssen SP, et al. Cellular and molecular insights into neuropathy-induced pain hypersensitivity for mechanism-based treatment approaches. Brain Res Rev. 2011;67(1-2):282–310.

    Article  CAS  PubMed  Google Scholar 

  76. Engineer ND, Riley JR, Seale JD, et al. Reversing pathological neural activity using targeted plasticity. Nature. 2011;470(7332):101–4.

    Article  PubMed Central  PubMed  Google Scholar 

  77. Tsao H, Galea MO, Hodges PW. Driving plasticity on the motor cortex in recurrent low back pain. Eur J Pain. 2010;14(8):832–9.

    Article  PubMed  Google Scholar 

  78. Boudreu SA, Farina D, Falla D. The role of motor learning and neuroplasticity in designing rehabilitation approaches for musculoskeletal pain disorders. Man Ther. 2010;15(5):410–4.

    Article  Google Scholar 

  79. Chipchase LS, Schabrun SM, Hodges PW. Peripheral electrical stimulation to induce cortical plasticity: as systematic review of stimulus parameters. Clin Neurophysiol. 2011;122(3):456–63.

    Article  CAS  PubMed  Google Scholar 

  80. Rottmann S, Jung K, Vohn R, Ellrich J. Long-term depression of pain-related cerebral activation in healthy man: an fMRI study. Eur J Pain. 2010;14(6):615–24.

    Article  PubMed  Google Scholar 

  81. Zhao HY, Mu P, Dong Y. The pathological neural plasticity and its applications in acupuncture. Zhen Ci Yan Jiu. 2008;33(1):41–6.

    PubMed  Google Scholar 

  82. Flor H, Diers M. Sensorimotor training and cortical reorganization. NeuroRehabilitation. 2009;25(1):19–27.

    PubMed  Google Scholar 

  83. Ramachandran VS, Altschuler EL. The use of visual feedback, in particular mirror visual feedback, in restoring brain function. Brain. 2009;132(Pt 7):1693–710.

    Article  CAS  PubMed  Google Scholar 

  84. Taylor HH, Murphy B. Altered central integration of dual somatosensory input after cervical spine manipulation. J Manipulative Physiol Ther. 2010;33(3):178–88.

    Article  PubMed  Google Scholar 

  85. Di Lazzaro V, Dileone M, Profice P, et al. Associative motor cortex plasticity: direct evidence in humans. Cereb Cortex. 2009;19(10):2326–30.

    Article  PubMed  Google Scholar 

  86. Di Lazzaro V, Dileone M, Profice P, et al. LTD-like plasticity induced by paired associative stimulation: direct evidence in humans. Exp Brain Res. 2009;194(4):661–4.

    Article  PubMed  Google Scholar 

  87. Fontán-Lozano A, López-Lluch G, Delgado-Garcia JM, et al. Molecular bases of caloric restriction regulation of neuronal synaptic plasticity. Mol Neurobiol. 2008;38(2):167–77.

    Article  PubMed  Google Scholar 

  88. Lahmann C, Henningsen P, Noll-Hussong M. Somatoform pain disorder-overview. Psychiatr Danub. 2010;22(3):453–8.

    PubMed  Google Scholar 

  89. Hay L. You can heal your life. Carlsbad: Hay House; 1999.

    Google Scholar 

  90. Satinover J. The quantum brain. New York: Wiley; 2001.

    Google Scholar 

  91. Hawkins D. Power vs Force. New York: Hay House; 2002.

    Google Scholar 

  92. Hawkins D. Healing and recovery. Sedona: Veritas Publishing; 2009.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The LITE Center, 5901 SW 74 St, Suite 201, South Miami, FL, 33143, USA

    Albert L. Ray M.D. (Medical Director, Clinical Associate Professor)

  2. University of Miami Miller School of Medicine, Miami, FL, USA

    Albert L. Ray M.D. (Medical Director, Clinical Associate Professor)

Authors
  1. Albert L. Ray M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Albert L. Ray M.D. .

Editor information

Editors and Affiliations

  1. President and CEO, Clinical Professor of Anesthesiology, The Center for Pain Relief, West Virginia University School of Medicine, Charleston, West Virginia, USA

    Timothy R. Deer

  2. Clinic Chief, Clinical Associate Professor, Department of Anesthesiology, Stanford Pain Medicine Center, Redwood City, CA, USA, and Stanford University School of Medicine, Stanford, California, USA

    Michael S. Leong

  3. Medical Director, Clinical Associate Professor, The LITE Center, South Miami, FL, USA, and University of Miami Miller School of Medicine, Miami, Florida, USA

    Albert L. Ray

Rights and permissions

Reprints and permissions

Copyright information

© 2015 American Academy of Pain Medicine

About this chapter

Cite this chapter

Ray, A.L. (2015). Neuroplasticity, Sensitization, and Pain. In: Deer, T., Leong, M., Ray, A. (eds) Treatment of Chronic Pain by Integrative Approaches. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1821-8_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1821-8_2

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-1820-1

  • Online ISBN: 978-1-4939-1821-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation