Skip to main content
SpringerLink
Log in
Book cover

Advances in Pain Research: Mechanisms and Modulation of Chronic Pain pp 211–227Cite as

Involvement of P2X7 Receptors and BDNF in the Pathogenesis of Central Poststroke Pain

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1099))

Abstract

Central pain is commonly found in patients with neurological complications that are associated with central nervous system insult, such as stroke. It can result directly from central nervous system injury. Impairments in sensory discrimination can make it challenging to differentiate central neuropathic pain from other types of pain or spasticity. Central neuropathic pain may also begin months to years after the injury, further obscuring the recognition of its association with past neurologic injury. This chapter focuses on the involvement of P2X7 receptor and brain-derived neurotrophic factor (BDNF) in central poststroke pain (CPSP). An experimental animal model is introduced that assesses the pathogenesis of central neuropathic pain, and pharmacological approaches and neuromodulatory treatments of this difficult-to-treat pain syndrome are discussed.

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   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
Hardcover Book
USD   179.99
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. International Association for the Study of Pain. IASP taxonomy. Retrieved from: http://www.iasp-pain.org/Taxonomy#Neuropathicpain. Updated October 6, 2014. Accessed 27 Mar 2018

  2. Watson JC, Sandroni P (2016) Central neuropathic pain syndromes. Mayo Clin Proc 91(3):372–385

    Article  PubMed  Google Scholar 

  3. Centers for Disease Control and Prevention. FastStats: leading causes of death. Updated September 30, 2015. Retrieved from: http://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Accessed 27 Mar 2018

  4. Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S et al (2018) Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation 137(12):e67–e492

    Article  PubMed  Google Scholar 

  5. Centers for Disease Control and Prevention (2009) Prevalence and most common causes of disability among adults: United States, 2005. Morb Mortal Wkly Rep 58(16):421–426

    Google Scholar 

  6. Tasker RR (2004) Central pain states. In: Warfield CA, Bajwa ZH (eds) Principles and practice of pain medicine, 2nd edn. McGraw-Hill, New York, pp 394–404

    Google Scholar 

  7. Bowsher D (1996) Central pain: clinical and physiological characteristics. J Neurol Neurosurg Psychiatry 61(1):62–69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bowsher D (2001) Stroke and central poststroke pain in an elderly population. J Pain 2:258–261

    Article  CAS  PubMed  Google Scholar 

  9. Kumar G, Soni CR (2009) Central post-stroke pain: current evidence. J Neurol Sci 284:10–17

    Article  PubMed  Google Scholar 

  10. Wang G, Thompson SM (2008) Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions. J Neurosci 28(46):11959–11969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Su YL, Huang J, Wang N, Wang JY, Luo F (2012) The effects of morphine on basal neuronal activities in the lateral and medial pain pathways. Neurosci Lett 525(2):173–178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhang Y, Wang N, Wang JY, Chang JY, Woodward DJ, Luo F (2011) Ensemble encoding of nociceptive stimulus intensity in the rat medial and lateral pain systems. Mol Pain 7:64

    Article  PubMed  PubMed Central  Google Scholar 

  13. Martin RJ, Apkarian AV, Hodge CJ Jr (1990) Ventrolateral and dorsolateral ascending spinal cord pathway influence on thalamic nociception in cat. J Neurophysiol 64(5):1400–1412

    Article  CAS  PubMed  Google Scholar 

  14. Craig AD, Bushnell MC, Zhang ET, Blomqvist A (1994) A thalamic nucleus specific for pain and temperature sensation. Nature 372(6508):770–773

    Article  CAS  PubMed  Google Scholar 

  15. Greenspan JD, Ohara S, Sarlani E, Lenz FA (2004) Allodynia in patients with post-stroke central pain (CPSP) studied by statistical quantitative sensory testing within individuals. Pain 109(3):357–366

    Article  CAS  PubMed  Google Scholar 

  16. Denk F, McMahon SB, Tracey I (2014) Pain vulnerability: a neurobiological perspective. Nat Neurosci 17(2):192–200

    Article  CAS  PubMed  Google Scholar 

  17. Sprenger T, Seifert CL, Valet M, Andreou AP, Foerschler A, Zimmer C et al (2012) Assessing the risk of central post-stroke pain of thalamic origin by lesion mapping. Brain 135(Pt 8):2536–2545

    Article  PubMed  Google Scholar 

  18. Kalita J, Kumar B, Misra UK, Pradhan PK (2011) Central post stroke pain: clinical, MRI, and SPECT correlation. Pain Med 12(2):282–288

    Article  PubMed  Google Scholar 

  19. Krause T, Brunecker P, Pittl S, Taskin B, Laubisch D, Winter B et al (2012) Thalamic sensory strokes with and without pain: differences in lesion patterns in the ventral posterior thalamus. J Neurol Neurosurg Psychiatry 83(8):776–784

    Article  PubMed  Google Scholar 

  20. Symonds LL, Gordon NS, Bixby JC, Mande MM (2006) Right-lateralized pain processing in the human cortex: an fMRI study. J Neurophysiol 95(6):3823–3830

    Article  PubMed  Google Scholar 

  21. Wasserman JK, Koeberle PD (2009) Development and characterization of a hemorrhagic rat model of central post-stroke pain. Neuroscience 161(1):173–183

    Article  CAS  PubMed  Google Scholar 

  22. Yang JW, Shih HC, Shyu BC (2006) Intracortical circuits in rat anterior cingulate cortex are activated by nociceptive inputs mediated by medial thalamus. J Neurophysiol 96(6):3409–3422

    Article  PubMed  Google Scholar 

  23. Llinas RR, Ribary U, Jeanmonod D, Kronberg E, Mitra PP (1999) Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci U S A 96(26):15222–15227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Shyu BC, Vogt BA (2009) Short-term synaptic plasticity in the nociceptive thalamic-anterior cingulate pathway. Mol Pain 5:51

    Article  PubMed  PubMed Central  Google Scholar 

  25. Walton KD, Llinas RR (2010) Central pain as a thalamocortical dysrhythmia: a thalamic efference disconnection? In: Kruger L, Light AR, Walton K (eds) Translational pain research. CRC Press, Boca Raton, pp 301–314

    Google Scholar 

  26. Llinas R, Urbano FJ, Leznik E, Ramirez RR, van Marle HJ (2005) Rhythmic and dysrhythmic thalamocortical dynamics: GABA systems and the edge effect. Trends Neurosci 28:325–333

    Article  CAS  PubMed  Google Scholar 

  27. Lenz FA, Kwan HC, Dostrovsky JO, Tasker RR (1989) Characteristics of the bursting pattern of action potentials that occurs in the thalamus of patients with central pain. Brain Res 496:357–360

    Article  CAS  PubMed  Google Scholar 

  28. Jeanmonod D, Magnin M, Morel A (1993) Thalamus and neurogenic pain: physiological, anatomical and clinical data. Neuroreport 4:475–478

    Article  CAS  PubMed  Google Scholar 

  29. Sarnthein J, Stern J, Aufenberg C, Rousson V, Jeanmonod D (2006) Increased EEG power and slowed dominant frequency in patients with neurogenic pain. Brain 129:55–64

    Article  PubMed  Google Scholar 

  30. Farber K, Kettenmann H (2006) Functional role of calcium signals for microglial function. Glia 54:656–665

    Article  PubMed  Google Scholar 

  31. Miras-Portugal MT, Diaz-Hernandez M, Giraldez L, Hervas C, Gomez-Villafuertes R, Sen RP et al (2003) P2X7 receptors in rat brain: presence in synaptic terminals and granule cells. Neurochem Res 28:1597–1605

    Article  CAS  PubMed  Google Scholar 

  32. Ireland MF, Noakes PG, Bellingham MC (2004) P2X7-like receptor subunits enhance excitatory synaptic transmission at central synapses by presynaptic mechanisms. Neuroscience 128:269–280

    Article  CAS  PubMed  Google Scholar 

  33. Alloisio S, Cervetto C, Passalacqua M, Barbieri R, Maura G, Nobile M et al (2008) Functional evidence for presynaptic P2X7 receptors in adult rat cerebrocortical nerve terminals. FEBS Lett 582:3948–3953

    Article  CAS  PubMed  Google Scholar 

  34. Peng W, Cotrina ML, Han X, Yu H, Bekar L, Blum L et al (2009) Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury. Proc Natl Acad Sci U S A 106:12489–12493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sarnthein J, Jeanmonod D (2008) High thalamocortical theta coherence in patients with neurogenic pain. Neuroimage 39:1910–1917

    Article  PubMed  Google Scholar 

  36. Stern J, Jeanmonod D, Sarnthein J (2006) Persistent EEG overactivation in the cortical pain matrix of neurogenic pain patients. Neuroimage 31:721–731

    Article  PubMed  Google Scholar 

  37. Lu Y, Zheng J, Xiong L, Zimmermann M, Yang J (2008) Spinal cord injury-induced attenuation of GABAergic inhibition in spinal dorsal horn circuits is associated with down-regulation of the chloride transporter KCC2 in rat. J Physiol 586:5701–5715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kuan YH, Shih HC, Lu HC, Tang SC, Jeng JS, Shyu BC (2015) Animal models of central post-stroke pain. Rec Dev Pain Res 2:1–18

    Google Scholar 

  39. Kuan YH, Shih HC, Tang SC, Jeng JS, Shyu BC (2015) Targeting P2X7 receptor for the treatment of central post-stroke pain in a rodent model. Neurobiol Dis 78:134–145

    Article  CAS  PubMed  Google Scholar 

  40. Kuan YH, Shyu BC (2016) Nociceptive transmission and modulation via P2X receptors in central pain syndrome. Mol Brain 9(1):58

    Article  PubMed  PubMed Central  Google Scholar 

  41. Shih HC, Kuan YH, Shyu BC (2017) Targeting brain-derived neurotrophic factor in the medial thalamus for the treatment of central poststroke pain in a rodent model. Pain 158(7):1302–1313

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

We thank the Taiwan Mouse Clinics for their suggestions on the behavioral tests. We are thankful for the technical support from the Neural Circuit Electrophysiology Core at Academia Sinica. The present study was supported by grants from the Ministry of Science and Technology to Dr. Bai-Chuang Shyu (105-2325-B-001-010, 105-2320-B-001-025-MY2, and 106-2321-B-001-043). This work was conducted at the Institute of Biomedical Sciences, which received funding from Academia Sinica.

Author information

Authors and Affiliations

  1. Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    Yung-Hui Kuan, Hsi-Chien Shih & Bai-Chuang Shyu

Authors
  1. Yung-Hui Kuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hsi-Chien Shih
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bai-Chuang Shyu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bai-Chuang Shyu .

Editor information

Editors and Affiliations

  1. Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    Bai-Chuang Shyu

  2. Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Okazaki, Aichi, Japan

    Makoto Tominaga

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kuan, YH., Shih, HC., Shyu, BC. (2018). Involvement of P2X7 Receptors and BDNF in the Pathogenesis of Central Poststroke Pain. In: Shyu, BC., Tominaga, M. (eds) Advances in Pain Research: Mechanisms and Modulation of Chronic Pain. Advances in Experimental Medicine and Biology, vol 1099. Springer, Singapore. https://doi.org/10.1007/978-981-13-1756-9_18

Download citation

Publish with us

Policies and ethics

Search

Navigation