Korean J Pain.  2011 Dec;24(4):191-198. 10.3344/kjp.2011.24.4.191.

Effects of Low and High Molecular Weight Hyaluronic Acids on Peridural Fibrosis and Inflammation in Lumbar Laminectomized Rats

• Lee JG
• Lee SC
• Kim YC
• Lim YJ
• Shin JH
• Kim JH
• Park SH
• Choi YR
• Sim WS

• KMID: 2074013
• DOI: http://doi.org/10.3344/kjp.2011.24.4.191

Abstract

BACKGROUND
Postlaminectomy peridural fibrosis is inevitable. Some studies have compared and identified the effects of high molecular weight hyaluronic acids (HMWHA) and low molecular weight hyaluronic acids (LMWHA) on peridural fibrosis in postlaminectomy animal models. However, no studies have been found that compare pain behaviors between hyaluronic acids or among hyaluronic acids and other solid materials. The purpose of this study was to examine the correlation between pain-related behaviors and histopathologic changes in laminectomized rats using various peridurally administered materials.
METHODS
Forty male Sprague-Dawley rats, laminectomized at the L5 and L6 levels, were divided into four groups: group C, laminectomy only; group L, laminectomy and LMWHA application; group H, laminectomy and HMWHA application; group F, laminectomy and fat interposition. Pain behaviors were checked before, 3 days, 1 week, and 3 weeks after surgery. Histopathological changes were checked at the L5 level 3 weeks after the surgery.
RESULTS
The 50% withdrawal thresholds in groups L and H were higher than that in groups C and F three days after laminectomy (P < 0.05). The paw withdrawal time did not change among the groups and in each group during the study period. Peridural fibrosis in group F was significantly lower than in the other groups (P < 0.05).
CONCLUSIONS
Hyaluronic acids significantly reduced mechanical allodynia but not thermal hyperalgesia. Peridural fibrosis did not show any correlation with pain behaviors. There have been limited studies on the correlation between peridural fibrosis and pain behavioral change, which should be verified by further studies.

Keyword

allodynia; failed back surgery syndrome; hyaluronic acid; laminectomy

MeSH Terms

Animals
Failed Back Surgery Syndrome
Fibrosis
Humans
Hyaluronic Acid
Hyperalgesia
Inflammation
Laminectomy
Male
Models, Animal
Molecular Weight
Rats
Rats, Sprague-Dawley
Hyaluronic Acid

Figure

• 

  Fig. 1 The grade of cauda equina clumping on the light microscopic findings at L5 or L6 level at the 21st day after laminectomy in ×10 scale (hematoxylin and eosin staining). In grade 1, most rootlets are distributed separately in the subarachnoid space. In grade 2, more than half of the rootlets are grouped to one another. In grade 3, all nerve rootlets are grouped or adhered to form a lump. In grade 4, severe peridural adhesion can be seen.

• 

  Fig. 2 The changes of 50% withdrawal threshold before laminectomy and 3 days, 1 week, and 3 weeks after laminectomy. Values are mean ± SE. Group C: laminectomy only, group L: laminectomy and low molecular weight hyaluronic acid application, group H: laminectomy and high molecular weight hyaluronic acid application, and group F: laminectomy and fat interposition. In groups C and F, 50% withdrawal thresholds are decreased significantly 3 days after laminectomy and maintained thereafter. Overall the mechanical allodynia in groups C and F are more significant than that of other groups from 3 days after laminectomy. *P < 0.05 vs. group C and †P < 0.05 vs. group F.

• 

  Fig. 3 The changes of paw withdrawal time before laminectomy and 3 days, 1 week, and 3 weeks after laminectomy. Values are mean ± SE. Group C: laminectomy only, group L: laminectomy and low molecular weight hyaluronic acid application, group H: laminectomy and high molecular weight hyaluronic acid application, and group F: laminectomy and fat interposition. There was no significant difference in thermal hyperalgesia among groups.

• 

  Fig. 4 The correlations between pain behaviors and histopathologic findings. (A) Correlations between 50% withdrawal threshold and grade of cauda equina adhesion. (B) Correlations between paw withdrawal time and grade of cauda equina adhesion. (C) Correlations between 50% withdrawal threshold and grade of eridural fibrosis. (D) Correlations between paw withdrawal time and grade of peridural fibrosis. Boxes are mean ± SD and center lines are means. It is supposed that the more the fibrotic change or cauda equina adhesion, the less the 50% withdrawal threshold or paw withdrawal time. However, there are no significant correlations between pain behaviors and histopathological findings.

• 

  Fig. 5 The correlations between pain behaviors and inflammatory cells count. It is supposed that the more the inflammatory change, the less the 50% withdrawal threshold or paw withdrawal time. However, there are no significant correlations between pain behaviors and inflammatory cell count. In graph (A) y0 = 9.5 and slope = -0.062 and in graph (B) y0 = 16.5 and slope = 0.019. y0 means y-intersect where x value is 0.

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