Gregory D. Cramer, DC, PhD, Charles N.R. Henderson, DC, PhD,
Joshua W. Little, DC, Clover Daley, BS, Thomas J. Grieve, DC
Department of Research,
National University of Health Sciences,
Lombard, IL 60510, USA.
OBJECTIVE: Adhesions (ADH) have been previously identified in many hypomobile joints, but not in the zygapophyseal (Z) joints of the spine. The objective of this study was to determine if connective tissue ADH developed in lumbar Z joints after induced intervertebral hypomobility (segmental fixation).
METHODS: Using an established rat model, 3 contiguous segments (L4, L5, L6) were fixed with specially engineered, surgically implanted, vertebral fixation devices. Z joints of experimental rats (17 rats, 64 Z joints) with 4, 8, 12, or 16 weeks of induced hypomobility were compared with Z joints of age-matched control rats (23 rats, 86 Z joints). Tissue was prepared for brightfield microscopy, examined, and photomicrographed. A standardized grading system identified small, medium, and large ADH and the average numbers of each per joint were calculated.
RESULTS: Connective tissue ADH were characterized and their location within Z joints described. Small and medium ADH were found in rats from all study groups. However, large ADH were found only in rats with 8, 12, or 16 weeks of experimentally induced intervertebral hypomobility. Significant differences among study groups were found for small (P < .003), medium (P < .000), and large (P < .000) ADH. The average number of medium and large ADH per joint increased with the length of experimentally induced hypomobility in rats with 8 and 16 weeks of induced hypomobility.
CONCLUSIONS: We conclude that hypomobility results in time-dependent ADH development within the Z joints. Such ADH development may have relevance to spinal manipulation, which could theoretically break up Z joint intra-articular ADHs.
From the FULL TEXT Article
Summary of Findings
We found that the assessment of Adhesions (ADH) was accomplished reliably and the light microscopic structure of the Z joint ADH could be clearly visualized and described (see subsection Nature and Source of ADH).
The ADH were approximately equal in numbers in the left and right Z joints and were most commonly found in the periphery of the Z joints, both along the medial and lateral (ie, the medial and lateral quadrants) and to a lesser extent the superior and inferior aspects of the joints (cephalad quadrant, medium ADH; caudad quadrant, large ADH). The number of ADH was generally related to the length of time a joint underwent induced hypomobility (see subsections Location_of_ADH and Time-Dependent Nature of ADH Development).
Several specific issues of this study can benefit from further discussion. These issues include: the effect of the surgery on the development of ADH, the nature and source of the ADH, the time-dependent nature of ADH development, the study’s limitations, and the potential clinical relevance and directions of future research. These issues are addressed in the following sections.
Effect of Surgery and the SAUs on the Development of ADH
The effect of the surgeries and/or the SAUs used to induce hypomobility in this study was of high importance in assessing the relevance of the research. If the surgeries or implanted SAUs contributed to the creation of intra-articular ADH, then the effects of hypomobility alone on ADH development would be difficult, or impossible, to evaluate. For this reason more control animals were used in this study than fixation animals (24 controls vs 17 fixation animals). The controls animals either had: no surgery at all (CSURG group); surgery with the spinous processes prepared for implantation of the SAUs, but the SAUs were not implanted (CSAU group); or they had the surgery and the SAUs implanted, but the SAUs were never linked together to create hypomobility (CLINK group). The CLINK animals were the most closely related to the experimental fixation animals, the only difference being that the linking device was never put in place. Th CLINK animals showed no difference from the other two types of controls, regardless of duration of survival (4, 8, 12, or 16 weeks) or type of ADH (small, medium, or large), yet the control animals were significantly different from the fixation animals in many categories. The same held true for the (CSAU) animals. Recall that these animals had surgery but the SAUs were not implanted. This group also showed no difference from the other control animals, including the CSURG Group that had no surgery at all. These findings indicate that neither the surgical procedures themselves nor the implantation of SAUs had an effect on ADH development. Consequently, we are confident that the differences found between the experimental fixation animals and the control animals represent the effects of hypomobility and not the effects of the surgical procedures or the implantation devices (SAUs).
Nature and Source of ADH
Small ADH were composed primarily of loose connective tissue; medium ADH were most variable and composed either of dense irregular connective tissue (if the connective tissue fibers were irregularly arranged) or dense regular connective tissue (if the fibers were regularly arranged) and large ADH were composed primarily of dense irregular connective tissue.
Hase  addressed the issue of the source of intra-articular ADH in his study of the TMJ. He was convinced that the ADH were the result of a “deposition of fibrinoid material” secondary to “degeneration of type-A cells of the synovial membrane.”  Although the TMJs are modified fibrous joints and the Z joints are planar synovial joints, the same mechanism is reasonable for the Z joints, because the Z joints have an ample synovium found not only along the inner joint capsule but also surrounding the Z joint synovial folds. [20, 21] Further research is required to verify the source of Z joint intra-articular ADH. Additional work characterizing the ultrastructural and biochemical composition of the ADH is also warranted.
Location of ADH
The ADH were most abundant along the periphery of the Z joints (primarily the medial and lateral quadrants, but also to a lesser extent the cephalad and caudad quadrants). Even though large and medium ADH were significantly more abundant along the periphery, the medium ADH in the F16 group also extended into the more central quadrants of the Z joints. The most likely explanation of this is that the Z joint synovial folds are located along the periphery of the joints, and the broad capsular attachment sites of these folds lie along the medial and lateral aspects of the joints. Recall that Hase  believed the ADH he found in the TMJ were caused by the breakdown of synoviocytes, which would leave small joint inclusions around which collagen-based ADH could develop. The synoviocyte-rich Z joint synovial folds provide an abundant source of synoviocytes whose natural (and relatively rapid) turnover may present a plentiful source of small joint inclusions around which Z joint ADH could develop. Again, further ultrastructural and biochemical analysis focusing on the formation of the ADH is needed to better understand why the ADH are more prominent along the periphery of hypomobile Z joints.
Time-Dependent Nature of ADH Development
The number of ADH was generally directly related to the length of time a joint underwent induced hypomobility. Small ADH were common in the Z joints of control and fixation rats; however, medium and large ADH seemed closely related to the duration of hypomobility (spinal fixation) with significant differences found between 16 week control and fixation animals for all sizes of ADH. Although slightly more medium and large ADH were found in 8-week fixation animals compared to 12-week fixation animals, the differences were not significant.
The results indicate that although small ADH are relatively common, medium and large ADH develop with increasing durations of hypomobility, suggesting that small ADH may develop into medium or eventually large ADH with continued hypomobility. One possible interpretation of these findings is that small ADH act as “seed structures” that are in dynamic equilibrium, that is, building up and breaking down, depending on the absence or presence of joint motion. Consequently, ADH may build up and, possibly, become irreversible with chronic hypomobility of a joint. This might explain the finding that in 16-week fixation animals (the maximum survival length in this study), medium ADH were found not only in the periphery of the joint, but also more centrally as well, an indication that small ADH had enlarged into medium ADH. One might anticipate that with longer periods of hypomobility, the medium ADH would further develop into large ADH. A study similar to that reported here, but extending the fixation period to 20 and 24 weeks would help to confirm this hypothesis. One might also speculate that the rapid Z joint motion (gapping) induced by spinal manipulation may act to modulate such a dynamic ADH development system. This is conjecture and more research is needed to clarify the role spinal manipulation may play in modulating ADH development.
A relatively small number of animals were available for some of the control subgroups and only three animals were available in the 12- and 16-week fixation groups. Consequently, some caution should be used when interpreting the data. However, the total number of joints was relatively high and the changes were significant in several areas (eg, 16-week control vs 16-week fixation animals for small, medium, and large ADH), indicating that the findings reported here are due to real differences.
A large number of statistical tests were performed to analyze the secondary outcome of ADH location within the joint. Although we are confident the results provide useful information regarding the location of ADH within this study, further research with larger numbers of animals is needed to reach the statistical power necessary to assess ADH location as a primary outcome.
In addition, this study did not assess the ultrastructure or biochemical make up of the ADH. Such analyses in future investigations could provide useful information regarding the origins and the nature of the ADH, and the possible mechanisms by which ADH development in the Z joints could be slowed and/or their breakdown enhanced by therapeutic interventions. Clinical Relevance and Future Research
These findings are consistent with the hypothesis that joint hypomobility leads to increased ADH development (Fig 1). The results reported here are also consistent with previously reported findings that osteophyte formation and degenerative changes of the articular facets increase with induced hypomobility.3 Additional research is needed to determine the clinical significance of both ADH size and the effects of spinal manipulation on Z joint ADH. Experiments assessing the effects of standardized high-velocity, low-amplitude thrusts and low-velocity, variable-amplitude mobilizations on degenerative changes of the Z joints in this animal model are currently underway.
Experimentally induced segmental hypomobility (fixation) of the lumbar Z joints resulted in time dependent intra-articular ADH formation. The ADH were found in approximately equal numbers in the left and right Z joints and were most prevalent in the peripheral regions of the joint from medial to lateral and cephalad to caudal. These findings are consistent with the hypothesis that hypomobility results in time-dependent degenerative changes and ADH development of the Z joints.
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