The Journal of Korean Physical Therapy

The Korean Society of Physical Therapy (대한물리치료학회)
권호 표지

Development of Neuropathic Pain Behavior and Expression of CCL2/CCR2 and CX3CL1/CX3CR1 after Spinal Cord Hemisection

  • Park, Hea-Woon (Department of Rehabilitation Medicine, School of Medicine, Catholic University of Deagu) ;
  • Son, Jo-Young (Department of Rehabilitation Medicine, School of Medicine, Catholic University of Deagu) ;
  • Cho, Yun-Woo (Department of Rehabilitation Medicine, College of Medicine, Yeungnam University) ;
  • Hwang, Se-Jin (Department of Anatomy and Cell Biology, College of Medicine, Hanyang University) ;
  • Kim, Su-Jeong (Institute of Medical Science, Yeungnam University) ;
  • Ahn, Sang-Ho (Department of Rehabilitation Medicine, College of Medicine, Yeungnam University) ;
  • Jang, Sung-Ho (Department of Rehabilitation Medicine, College of Medicine, Yeungnam University) ;
  • Jung, Yong-Jae (Department of Rehabilitation Medicine, College of Medicine, Yeungnam University)
  • Received : 2010.05.19
  • Accepted : 2010.06.15
  • Published : 2010.06.25
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: The purpose of this study was to evaluate the development of pain behavior and the expression of CCL2/CCR2 and CX3CL1/CX3CR1 at above and below the level of hemisection of the spinal cord in a rat model. Methods: Spinal cords of adult female Sprague-Dawley rats (n= 16, 200~250 g, 6~8 weeks old) were hemisected at T13 on the right side to develop the spinal hemisection injury model. We compared behavioral responses of the hemisection and of a sham surgery group. Behavioral tests for motor function (by the BBB locomotor scale), and for pain response for mechanical and cold allodynia were assessed postoperatively (PO) for 21 days. Expression of mRNA for chemokines and their receptors (CCL2/CCR2 and CX3CL1/CX3CR1) below and above the level of the spinal cord dissection were examined by RT-PCR. Results: We observed gradual motor improvement and the development of mechanical and cold allodynia on the ipsilateral hindpaw after spinal hemisection injury. We also found upregulation of mRNA expression of CCL2/CCR2 both above and below the level of spinal cord dissection but CX3CL1/CX3CR1 mRNA expression. Conclusion: Upregulation of CCL2/CCR2 is associated with neuropathic pain after spinal hemisection injury. CCL2/CCR2 may play an important role in the development of neuropathic pain after SCI as well as of peripheral neuropathic pain. These findings may improve understanding of the pathophysiological mechanism of neuropathic pain after SCI.

Keywords

References

  1. Siddall PJ, McClelland JM, Rutkowski SB et al. A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury. Pain. 2003; 103(3):249-57. https://doi.org/10.1016/S0304-3959(02)00452-9
  2. Yezierski RP. Pain following spinal cord injury: the clinical problem and experimental studies. Pain. 1996;68(2-3):185- 94. https://doi.org/10.1016/S0304-3959(96)03178-8
  3. Abbadie C, Bhangoo S, De Koninck Y et al. Chemokines and pain mechanisms. Brain Res Rev. 2009;60(1):125-34. https://doi.org/10.1016/j.brainresrev.2008.12.002
  4. Thacker MA, Clark AK, Bishop T et al. CCL2 is a key mediator of microglia activation in neuropathic pain states. Eur J Pain. 2009;13(3):263-72. https://doi.org/10.1016/j.ejpain.2008.04.017
  5. White FA, Jung H, Miller RJ. Chemokines and the pathophysiology of neuropathic pain. Proc Natl Acad Sci U S A. 2007;104(51):20151-8.
  6. White FA, Wilson NM. Chemokines as pain mediators and modulators. Curr Opin Anaesthesiol. 2008;21(5):580-5. https://doi.org/10.1097/ACO.0b013e32830eb69d
  7. Zhuang ZY, Kawasaki Y, Tan PH et al. Role of the CX3CR1/ p38 MAPK pathway in spinal microglia for the development of neuropathic pain following nerve injury-induced cleavage of fractalkine. Brain Behav Immun. 2007;21(5):642-51. https://doi.org/10.1016/j.bbi.2006.11.003
  8. Hulsebosch CE, Hains BC, Crown ED et al. Mechanisms of chronic central neuropathic pain after spinal cord injury. Brain Res Rev. 2009;60(1):202-13. https://doi.org/10.1016/j.brainresrev.2008.12.010
  9. Knerlich-Lukoschus F, Juraschek M, Blomer U et al. Forcedependent development of neuropathic central pain and time-related CCL2/CCR2 expression after graded spinal cord contusion injuries of the rat. J Neurotrauma. 2008;25(5): 427-48. https://doi.org/10.1089/neu.2007.0431
  10. Christensen MD, Everhart AW, Pickelman JT et al. Mechanical and thermal allodynia in chronic central pain following spinal cord injury. Pain. 1996;68(1):97-107. https://doi.org/10.1016/S0304-3959(96)03224-1
  11. Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12(1):1-21. https://doi.org/10.1089/neu.1995.12.1
  12. Chaplan SR, Bach FW, Pogrel JW et al. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994; 53(1):55-63. https://doi.org/10.1016/0165-0270(94)90144-9
  13. Choi Y, Yoon YW, Na HS et al. Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain. 1994;59(3):369-76. https://doi.org/10.1016/0304-3959(94)90023-X
  14. Kim J, Yoon YW, Hong SK et al. Cold and mechanical allodynia in both hindpaws and tail following thoracic spinal cord hemisection in rats: time courses and their correlates. Neurosci Lett. 2003;343(3):200-4. https://doi.org/10.1016/S0304-3940(03)00377-X
  15. Detloff MR, Fisher LC, McGaughy V et al. Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats. Exp Neurol. 2008;212(2):337-47. https://doi.org/10.1016/j.expneurol.2008.04.009
  16. Yoon YW, Dong H, Arends JJ et al. Mechanical and cold allodynia in a rat spinal cord contusion model. Somatosens Mot Res. 2004;21(1):25-31. https://doi.org/10.1080/0899022042000201272
  17. Watkins LR, Milligan ED, Maier SF. Glial activation: a driving force for pathological pain. Trends Neurosci. 2001;24(8):450-5. https://doi.org/10.1016/S0166-2236(00)01854-3
  18. Ji RR, Strichartz G. Cell signaling and the genesis of neuropathic pain. Sci STKE. 2004;2004(252):reE14.
  19. Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat Rev Neurosci. 2005;6(7):521-32.
  20. Jung H, Toth PT, White FA et al. Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons. J Neurochem. 2008;104(1):254-63.
  21. White FA, Sun J, Waters SM et al. Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion. Proc Natl Acad Sci U S A. 2005;102(39):14092-7. https://doi.org/10.1073/pnas.0503496102
  22. Zhang J, Shi XQ, Echeverry S et al. Expression of CCR2 in both resident and bone marrow-derived microglia plays a critical role in neuropathic pain. J Neurosci. 2007;27(45): 12396-406. https://doi.org/10.1523/JNEUROSCI.3016-07.2007