Preliminary Morphological Evidence That Vertebral
Hypomobility Induces Synaptic Plasticity
in the Spinal Cord

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

FROM:   J Manipulative Physiol Ther. 2007 (Jun); 30 (5): 336–342 ~ FULL TEXT

Barclay W. Bakkum, DC, Charles N.R. Henderson, DC, PhD,
Se-Pyo Hong, DC, PhD, Gregory D. Cramer, DC, PhD

Department of Basic and Health Sciences,
Illinois College of Optometry,
Chicago, Ill 60616, USA.
bbakkum@ico.edu

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OBJECTIVE:   A widely accepted theoretical model suggests that vertebral hypomobility can cause pain and abnormal spinal mechanics because of changes in sensory input from spinal and paraspinal tissues. The purpose of this pilot study was 3-fold:

(1) to make a preliminary determination if chronic vertebral hypomobility at L4 through L6 in the rat would affect synaptic density and/or morphology in the superficial dorsal horn of the L2 spinal cord level,

(2) to identify relevant outcome variables for future studies, and

(3) to obtain preliminary data that would permit estimating an appropriate sample size for future studies.

METHODS:   Using an established rat model, we fixed 3 contiguous lumbar segments (L4-L6) for 8 weeks with a specially engineered vertebral fixation device. Electron micrographs were obtained from 2 animals from the experimental (fixed) group and each of 3 control groups (no surgery, surgery but no devices implanted, and devices implanted but not fixed). Synapses were randomly selected using a stereological approach and were analyzed for symmetry, curvature, type of postsynaptic profile, and perforations. The synaptic density was also estimated.

RESULTS:   There was increased synaptic density and percentage of positively curved synapses in the dorsal horn of experimental animals as compared with controls. Experimental animals had a lower percentage of axospinous synapses, with a concomitant increase in the percentage of synapses on dendritic shafts.

CONCLUSIONS:   These preliminary data suggest for the first time that chronic vertebral hypomobility at L4 through L6 in the rat affects synaptic density and morphology in the superficial dorsal horn of the L2 spinal cord level. More definitive studies are warranted, and the biologic significance of these finding should be investigated.

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From the FULL TEXT Article

Introduction

A widely accepted theoretical model suggests that vertebral hypomobility can cause pain and abnormal spinal mechanics because of changes in sensory input from spinal and paraspinal tissues. [1, 2] Until recently, this hypothesis has been difficult to test because of the lack of a suitable animal model. With the introduction of a successful rat model of chronic vertebral hypomobility, [3, 4] it should be possible to test this hypothetical link between vertebral function and nervous system.

Activity-dependent plasticity is known to occur in the spinal cord throughout life. [5] These neurophysiologic changes appear to be driven by input from the periphery and the brain. They play an important role in the effects of spinal cord injury and other central nervous system disorders, along with the acquisition and maintenance of motor skills. Less is known about the morphological correlates associated with these physiologic adaptations.

Synapses are thought to be primary structures in neuroplastic change undergoing modifications in synaptic density, symmetry, curvature, and perforations of the postsynaptic density (PSD), as part of this process. [6, 7] Change in the type of postsynaptic profile (eg, dendritic spine, dendritic shaft, or soma) is also thought to play an important role. [8]

Chronic vertebral hypomobility as a cause of neuroplastic change within the spinal cord has not been previously reported. The purpose of this study was to make a preliminary determination if chronic vertebral hypomobility at L4 through L6 in the rat would affect synaptic density and/or morphology in the superficial dorsal horn of the L2 spinal cord level. The L2 spinal cord segment receives small-caliber afferent input from the L4–5 and L5–6 zygapophysial joints in the rat. [9–11] The superficial dorsal horn (Rexed's laminae I and II) is a primary termination site for small caliber (A? and C fibers) associated with pain mechanisms in both the human and the rat. [12–14] Successful demonstration of neuroplastic spinal cord changes in this pilot study would provide “proof of concept” justification and sample size data that are necessary for designing a larger definitive study of vertebral hypomobility as a cause of morphological changes in dorsal horn synapses.

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Discussion

These data offer the first anatomical evidence that altered spinal mechanics may produce neuroplastic changes in the dorsal horn of the spinal cord. These interesting findings suggest the need for larger definitive studies.

It has been hypothesized that positively curved synapses are more active synapses, whereas negatively curved synapses are thought to be less active or inactive. [7, 21, 22] Therefore, the increased percentage of positively curved synapses, along with the increased number of synapses, in the experimental animals compared with the controls may indicate an increase in synaptic activity in the dorsal horn of animals with hypomobile (fixated) vertebrae.

In addition, previous studies suggest that axospinous synapses are generally excitatory in nature. [8] Our small sample size precludes a definitive determination, but the decreased proportion of axospinous synapses seen in the experimental animals compared with the controls is consistent with a decreased amount of excitatory synaptic activity in the dorsal horn of animals with hypomobile (fixated) vertebrae.

Relatively few axosomatic synapses were observed in this study because the sampling strategy was not designed to capture cell bodies, the profiles of which occur much less frequently than synapses in tissue sections. Axosomatic synapses, by their proximity to the site where action potentials are generated, may be very important in determining neuronal activity. Specific studies to determine the effect of vertebral hypomobility on axosomatic synapse morphology, using unbiased sampling strategies that include at least 200 axosomatic synapses, should be conducted.

The relative numbers of perforated synapses identified in this study were either similar to or lower than those percentages of this type of synapse identified in other regions of the central nervous system. [8] Follow-up studies, with more power to capture this type of synapse, which has been linked to neuroplasticity, should be conducted.

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Conclusion

These preliminary data suggest that chronic vertebral hypomobility (fixation) at L4 through L6 in the rat affects synaptic density and morphology in the superficial dorsal horn of the L2 spinal cord level. Morphological parameters that appear to be affected include synaptic curvature, type of postsynaptic profile, and perforations of the PSD. Additional more definitive studies are warranted, and the biologic significance of these finding should be investigated.

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