Browse > Article

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)
Publication Information
The Journal of Korean Physical Therapy / v.22, no.3, 2010 , pp. 99-105 More about this Journal
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
Spinal cord injury; Neuropathic pain; Chemokine; CCL2/CCR2; CX3CL1/CX3CR1;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Watkins LR, Milligan ED, Maier SF. Glial activation: a driving force for pathological pain. Trends Neurosci. 2001;24(8):450-5.   DOI   ScienceOn
2 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.   DOI   ScienceOn
3 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.   DOI   ScienceOn
4 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.   DOI   ScienceOn
5 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.   DOI   ScienceOn
6 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.
7 Yezierski RP. Pain following spinal cord injury: the clinical problem and experimental studies. Pain. 1996;68(2-3):185- 94.   DOI   ScienceOn
8 Abbadie C, Bhangoo S, De Koninck Y et al. Chemokines and pain mechanisms. Brain Res Rev. 2009;60(1):125-34.   DOI
9 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.   DOI   ScienceOn
10 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.   DOI   ScienceOn
11 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.   DOI   ScienceOn
12 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.
13 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.   DOI   ScienceOn
14 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.   DOI   ScienceOn
15 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.   DOI
16 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.   DOI   ScienceOn
17 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.   DOI   ScienceOn
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 White FA, Wilson NM. Chemokines as pain mediators and modulators. Curr Opin Anaesthesiol. 2008;21(5):580-5.   DOI   ScienceOn
21 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.   DOI
22 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.   DOI   ScienceOn