Korean J Pain.  2016 Apr;29(2):86-95. 10.3344/kjp.2016.29.2.86.

Comparison of Mechanical Allodynia and Recovery of Locomotion and Bladder Function by Different Parameters of Low Thoracic Spinal Contusion Injury in Rats

Affiliations
  • 1Department of Neuroscience and Cell Biology, University of Texas Medical Branch at Galveston, TX, USA.
  • 2Department of Physiology, Daegu Haany University, Daegu, Korea. ysgwak@dhu.ac.kr

Abstract

BACKGROUND
The present study was designed to examine the functional recovery following spinal cord injury (SCI) by adjusting the parameters of impact force and dwell-time using the Infinite Horizon (IH) impactor device.
METHODS
Sprague-Dawley rats (225-240 g) were divided into eight injury groups based on force of injury (Kdyn) and dwell time (seconds), indicated as Force-Dwell time: 150-4, 150-3, 150-2, 150-1, 150-0, 200-0, 90-2 and sham controls, respectively.
RESULTS
After T10 SCI, higher injury force produced greater spinal cord displacement (P < 0.05) and showed a significant correlation (r = 0.813) between the displacement and the force (P < 0.05). In neuropathic pain-like behavior, the percent of paw withdrawals scores in the hindpaw for the 150-4, 150-3, 150-2, 150-1 and the 200-0 injury groups were significantly lowered compared with sham controls (P < 0.05). The recovery of locomotion had a significant within-subjects effect of time (P < 0.05) and the 150-0 group had increased recovery compared to other groups (P < 0.05). In addition, the 200-0 and the 90-2 recovered significantly better than all the 150 kdyn impact groups that included a dwell-time (P < 0.05). In recovery of spontaneous bladder function, the 150-4 injury group took significantly longer recovery time whereas the 150-0 and the 90-2 groups had the shortest recovery times.
CONCLUSIONS
The present study demonstrates SCI parameters optimize development of mechanical allodynia and other pathological outcomes.

Keyword

Blood brain barrier; Bladder function; Locomotion; Neuropathic pain; Spinal cord injury; Parameters; Rats

MeSH Terms

Animals
Blood-Brain Barrier
Contusions*
Hyperalgesia*
Locomotion*
Neuralgia
Rats*
Rats, Sprague-Dawley
Spinal Cord
Spinal Cord Injuries
Urinary Bladder*

Figure

  • Fig. 1 The relationship between actual force of impact and actual spinal cord displacement. All programmed injury mode produced consistent actual injury outcomes. In comparison of injury force (A) and displacement (B), the 200 kdyn group (*P < 0.05) and 90 kydn group (#P < 0.05) showed significant difference compared to 150 kdyn group, respectively. However, the all 150 kdyn groups did not show significant differences, suggesting the programmed injury mode produced consistent outcomes. (C) Scatter plot with linear regression graph revealed significant correlation between the actual force and the tissue displacement. Data are plotted as mean ± S.E.

  • Fig. 2 BBB rank scores of hindlimb locomotor function after SCI with varying impact forces and dwell-times. (A) The 150 kdyn with no dwell-time (150-0) group (*P < 0.05) showed the most improvement over time. Five days after SCI, 200-0 and 90-2 groups showed significant differences compared to 150-3 group (#P < 0.05). (B) The 150-0 group resulted in a significantly higher BBB score than all other injury groups at this time point (*P < 0.05). The both 200-0 and 90-2 groups showed significant differences compared with 150-0 groups (#P < 0.05). Data are plotted as mean ± S.E.

  • Fig. 3 Histogram of paws withdrawal responsiveness to von Frey filaments. Mechanical allodynia was evident at both forelimbs (A) and hindlimbs (B), respectively. 150 kdyn with dwell time groups showed mechanical allodynia at both 4 and 5 wks after SCI whereas other groups showed variable patterns. (*P < 0.05 for 4 weeks and $P < 0.05 for 5 weeks compared to sham group, respectively). Data are plotted as mean ± S.E.

  • Fig. 4 The duration of bladder dysfunction until onset of spontaneous bladder voiding. Note that the 150-4 group took significantly longer to recover function than all other groups (*P < 0.05). The 150-0 and 90-2 groups showed significant differences compared with 150 kdyn with dwell time groups (#P < 0.05). Additionally, the 200-0 injury group recovered more quickly than the 150-1 and 150-2 groups ($P < 0.05). Data are shown as mean days post-injury for full bladder voiding ± S.E.


Reference

1. Bruce JC, Oatway MA, Weaver LC. Chronic pain after clip-compression injury of the rat spinal cord. Exp Neurol. 2002; 178:33–48. PMID: 12460606.
Article
2. Mills CD, Grady JJ, Hulsebosch CE. Changes in exploratory behavior as a measure of chronic central pain following spinal cord injury. J Neurotrauma. 2001; 18:1091–1105. PMID: 11686495.
Article
3. Vierck CJ Jr, Light AR. Allodynia and hyperalgesia within dermatomes caudal to a spinal cord injury in primates and rodents. Prog Brain Res. 2000; 129:411–428. PMID: 11098708.
Article
4. Lindsey AE, LoVerso RL, Tovar CA, Hill CE, Beattie MS, Bresnahan JC. An analysis of changes in sensory thresholds to mild tactile and cold stimuli after experimental spinal cord injury in the rat. Neurorehabil Neural Repair. 2000; 14:287–300. PMID: 11402879.
Article
5. Hulsebosch CE, Xu GY, Perez-Polo JR, Westlund KN, Taylor CP, McAdoo DJ. Rodent model of chronic central pain after spinal cord contusion injury and effects of gabapentin. J Neurotrauma. 2000; 17:1205–1217. PMID: 11186233.
Article
6. Yezierski RP, Liu S, Ruenes GL, Kajander KJ, Brewer KL. Excitotoxic spinal cord injury: behavioral and morphological characteristics of a central pain model. Pain. 1998; 75:141–155. PMID: 9539683.
Article
7. Christensen MD, Everhart AW, Pickelman JT, Hulsebosch CE. Mechanical and thermal allodynia in chronic central pain following spinal cord injury. Pain. 1996; 68:97–107. PMID: 9252004.
Article
8. Siddall P, Xu CL, Cousins M. Allodynia following traumatic spinal cord injury in the rat. Neuroreport. 1995; 6:1241–1244. PMID: 7669978.
Article
9. Ovelmen-Levitt J, Gorecki J, Nguyen KT, Iskandar B, Nashold BS Jr. Spontaneous and evoked dysesthesias observed in the rat after spinal cordotomies. Stereotact Funct Neurosurg. 1995; 65:157–160. PMID: 8916347.
Article
10. Xu XJ, Hao JX, Aldskogius H, Seiger A, Wiesenfeld-Hallin Z. Chronic pain-related syndrome in rats after ischemic spinal cord lesion: a possible animal model for pain in patients with spinal cord injury. Pain. 1992; 48:279–290. PMID: 1589248.
Article
11. Hao JX, Xu XJ, Aldskogius H, Seiger A, Wiesenfeld-Hallin Z. Allodynia-like effects in rat after ischaemic spinal cord injury photochemically induced by laser irradiation. Pain. 1991; 45:175–185. PMID: 1652116.
Article
12. Bunge RP, Puckett WR, Becerra JL, Marcillo A, Quencer RM. Observations on the pathology of human spinal cord injury. A review and classification of 22 new cases with details from a case of chronic cord compression with extensive focal demyelination. Adv Neurol. 1993; 59:75–89. PMID: 8420126.
13. Kakulas BA, Taylor JR. Pathology of injuries of the vertebral column and spinal cord. In : Vinken PJ, Bruyn GW, Klawans HL, Frankel HL, editors. Handbook of clinical neurology. Vol 17. Amsterdam: Elsevier;1992. p. 21–51.
14. Metz GA, Curt A, van de Meent H, Klusman I, Schwab ME, Dietz V. Validation of the weight-drop contusion model in rats: a comparative study of human spinal cord injury. J Neurotrauma. 2000; 17:1–17. PMID: 10674754.
Article
15. Basso DM, Beattie MS, Bresnahan JC. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol. 1996; 139:244–256. PMID: 8654527.
Article
16. Constantini S, Young W. The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord injury in rats. J Neurosurg. 1994; 80:97–111. PMID: 8271028.
Article
17. Gruner JA. A monitored contusion model of spinal cord injury in the rat. J Neurotrauma. 1992; 9:123–126. PMID: 1404425.
Article
18. Wrathall JR, Pettegrew RK, Harvey F. Spinal cord contusion in the rat: production of graded, reproducible, injury groups. Exp Neurol. 1985; 88:108–122. PMID: 3979505.
Article
19. Stokes BT, Noyes DH, Behrmann DL. An electromechanical spinal injury technique with dynamic sensitivity. J Neurotrauma. 1992; 9:187–195. PMID: 1474607.
Article
20. Stokes BT. Experimental spinal cord injury: a dynamic and verifiable injury device. J Neurotrauma. 1992; 9:129–131. PMID: 1404426.
Article
21. Scheff SW, Rabchevsky AG, Fugaccia I, Main JA, Lumpp JE Jr. Experimental modeling of spinal cord injury: characterization of a force-defined injury device. J Neurotrauma. 2003; 20:179–193. PMID: 12675971.
Article
22. Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995; 12:1–21. PMID: 7783230.
Article
23. Pikov V, Wrathall JR. Coordination of the bladder detrusor and the external urethral sphincter in a rat model of spinal cord injury: effect of injury severity. J Neurosci. 2001; 21:559–569. PMID: 11160435.
Article
24. Christensen MD, Hulsebosch CE. Chronic central pain after spinal cord injury. J Neurotrauma. 1997; 14:517–537. PMID: 9300563.
Article
25. Choi Y, Yoon YW, Na HS, Kim SH, Chung JM. Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain. 1994; 59:369–376. PMID: 7708411.
Article
26. Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain. 1992; 50:355–363. PMID: 1333581.
Article
27. Wrathall JR, Emch GS. Effect of injury severity on lower urinary tract function after experimental spinal cord injury. Prog Brain Res. 2006; 152:117–134. PMID: 16198697.
Article
28. Streijger F, Beernink TM, Lee JH, Bhatnagar T, Park S, Kwon BK, et al. Characterization of a cervical spinal cord hemicontusion injury in mice using the infinite horizon impactor. J Neurotrauma. 2013; 30:869–883. PMID: 23360150.
Article
29. Kato H, Kanellopoulos GK, Matsuo S, Wu YJ, Jacquin MF, Hsu CY, et al. Neuronal apoptosis and necrosis following spinal cord ischemia in the rat. Exp Neurol. 1997; 148:464–474. PMID: 9417826.
Article
30. Rokkas CK, Cronin CS, Nitta T, Helfrich LR Jr, Lobner DC, Choi DW, et al. Profound systemic hypothermia inhibits the release of neurotransmitter amino acids in spinal cord ischemia. J Thorac Cardiovasc Surg. 1995; 110:27–35. PMID: 7609553.
Article
31. Taira Y, Marsala M. Effect of proximal arterial perfusion pressure on function, spinal cord blood flow, and histopathologic changes after increasing intervals of aortic occlusion in the rat. Stroke. 1996; 27:1850–1858. PMID: 8841344.
Article
32. Rivlin AS, Tator CH. Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg Neurol. 1978; 10:38–43. PMID: 684604.
33. Anderson KD. Targeting recovery: priorities of the spinal cord-injured population. J Neurotrauma. 2004; 21:1371–1383. PMID: 15672628.
Article
34. Ward PJ, Hubscher CH. Persistent polyuria in a rat spinal contusion model. J Neurotrauma. 2012; 29:2490–2498. PMID: 22708983.
Article
35. Sharp K, Yee KM, Steward O. A re-assessment of the effects of treatment with an epidermal growth factor receptor (EGFR) inhibitor on recovery of bladder and locomotor function following thoracic spinal cord injury in rats. Exp Neurol. 2012; 233:649–659. PMID: 22078761.
Article
36. de Groat WC, Yoshimura N. Mechanisms underlying the recovery of lower urinary tract function following spinal cord injury. Prog Brain Res. 2006; 152:59–84. PMID: 16198694.
Article
37. David BT, Steward O. Deficits in bladder function following spinal cord injury vary depending on the level of the injury. Exp Neurol. 2010; 226:128–135. PMID: 20713043.
Article
38. Kennedy P, Frankel H, Gardner B, Nuseibeh I. Factors associated with acute and chronic pain following traumatic spinal cord injuries. Spinal Cord. 1997; 35:814–817. PMID: 9429260.
Article
39. Hicken BL, Putzke JD, Richards JS. Bladder management and quality of life after spinal cord injury. Am J Phys Med Rehabil. 2001; 80:916–922. PMID: 11821674.
Article
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