Cervical intervertebral disc degeneration induced by unbalanced dynamic and static forces: A novel in vivo rat model
ABSTRACT Establishment of a novel in vivo animal model of cervical spondylosis.
To investigate apoptotic, degenerative, and inflammatory changes occurring in the cervical intervertebral discs of rats.
Cervical degeneration occurs as the result of imbalance of both static and dynamic spinal stabilizers. The disc degeneration that occurs is characterized by increased local inflammation and increased apoptosis of intervertebral disc cells.
By excising the paraspinal musculature and posterior cervical spinal ligaments of rats, both static and dynamic cervical stabilizers were disrupted. The resultant biomechanical imbalance resulted in biochemical and histologic changes, which were characterized by light microscopy, electron microscopy, immunostaining, enzyme-linked immunosorbent assay, polymerase chain reaction, and in situ hybridization.
Histologic analysis showed characteristic degenerative changes of the intervertebral discs and vertebral endplates following surgery. Ultrastructural examination revealed apoptotic changes, which were verified by immunostaining. Instability also resulted in significant up-regulation of inflammatory factors, as shown by enzyme-linked immunosorbent assay, polymerase chain reaction, and in situ hybridization.
By creating static and dynamic posterior instability of the cervical spine, this novel model of cervical spondylosis results in rapid intervertebral disc degeneration characterized by increased apoptosis and local inflammation, such as that seen clinically.
[Show abstract] [Hide abstract]
ABSTRACT: Evidence has shown that osteoporosis or intervertebral disc degeneration (IDD) led to cartilage endplate lesions (CEL), but their combined effects on the lesion remain unknown. This study developed an innovative rat model combined ovariectomy (OVX) and cervical muscle section (CMS), and aimed to evaluate the combined effects of osteoporosis and IDD on cartilage endplate lesions of cervical spine. Fifty-two Sprague-Dawley female rats were assigned randomly into four groups as follows: the sham group (n = 10) underwent sham surgery; the OVX group (n = 14) was subjected to bilateral ovariectomy; the CMS group (n = 14) had posterior paraspinal muscles cut from C2 to C7; the CMS-OVX group (n = 14) underwent the OVX and CMS surgeries consecutively. Samples of C6-C7 segments were harvested at 12, 18 and 24 weeks post-surgery. Micro-CT analysis was performed to evaluate the CEL, intervertebral disc height (IDH) and structural indices. Histological analysis with Safranine O/fast green stain and histological score were used to observe the characteristics of the degenerative discs. Ovariectomy surgery resulted in significant changes of most structural indices of the C6 body, such as decrease of percent bone volume and number of bone trabecula at 12 weeks, and greater changes at 18 and 24 weeks. The CEL following CMS surgery was seen on the ventral, while the CEL in the OVX and sham groups on the peripheral. The CEL was greatest in the CMS-OVX group and significantly greater than that in the CMS and OVX groups at 12 and 18 weeks (P < 0.05). The CMS surgery resulted in significant IDH decrease at 12, 18 and 24 weeks (P < 0.05), while the OVX surgery resulted in mild IDH decrease when compared with the sham group. The IDH in the CMS-OVX group was significantly lower than that in the CMS group at 24 weeks (P < 0.05). Histological evaluation suggested cartilage endplate abrasion at 12 weeks, and in situ calcification at 18 and 24 weeks in the CMS and CMS-OVX groups. Disc degenerative scores were higher following CMS or OVX surgery, and correlated with the CEL and IDH (P < 0.01), respectively. The present study suggested that a combination of OVX and CMS led to more lesion of cartilage endplate than any one thereof, as well as more decrease of IDH. The lesion and IDH decrease were associated with the disc degeneration levels. The cartilage endplate was worn out at the early stage and calcified in situ later. The results indicate that osteoporosis may deteriorate the disc degeneration at specific time.European Spine Journal 05/2014; 23(9). DOI:10.1007/s00586-014-3324-9 · 2.47 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Object The purpose of this study was to evaluate the effects of chronic unpredictable stress on the intervertebral discs of rats. Methods The cellular events involved in injury- and stress-induced disc degeneration were investigated in male Wistar rats. Disc degeneration and apoptosis were evaluated using microscopic (light and electron) and molecular (immunoblotting and immunohistochemistry) methods. Corticosterone levels were used as markers of stress and measured by radioimmunoassay. Results The data gathered in this study showed that chronic unpredictable stress can significantly increase corticosterone levels. Furthermore, biochemical markers of apoptosis (that is, increases in the Bax/Bcl2 ratio and TUNEL reactivity [p < 0.05]) were observed in the stressed animals. Electron and light microscopy also showed disc degeneration and apoptotic cells in the experimental groups. Conclusions Taken together, these data demonstrated that chronic stress is most likely to be a risk factor for creating intervertebral disc degeneration and that programmed cell death may be one of the mechanisms of stress-induced disc degeneration.Journal of neurosurgery. Spine 03/2014; DOI:10.3171/2014.1.SPINE13466 · 2.36 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The use of conventional modalities for chronic neck pain remains debatable, primarily because most treatments have had limited success. We conducted a review of the literature published up to December 2013 on the diagnostic and treatment modalities of disorders related to chronic neck pain and concluded that, despite providing temporary relief of symptoms, these treatments do not address the specific problems of healing and are not likely to offer long-term cures. The objectives of this narrative review are to provide an overview of chronic neck pain as it relates to cervical instability, to describe the anatomical features of the cervical spine and the impact of capsular ligament laxity, to discuss the disorders causing chronic neck pain and their current treatments, and lastly, to present prolotherapy as a viable treatment option that heals injured ligaments, restores stability to the spine, and resolves chronic neck pain. The capsular ligaments are the main stabilizing structures of the facet joints in the cervical spine and have been implicated as a major source of chronic neck pain. Chronic neck pain often reflects a state of instability in the cervical spine and is a symptom common to a number of conditions described herein, including disc herniation, cervical spondylosis, whiplash injury and whiplash associated disorder, postconcussion syndrome, vertebrobasilar insufficiency, and Barré-Liéou syndrome. When the capsular ligaments are injured, they become elongated and exhibit laxity, which causes excessive movement of the cervical vertebrae. In the upper cervical spine (C0-C2), this can cause a number of other symptoms including, but not limited to, nerve irritation and vertebrobasilar insufficiency with associated vertigo, tinnitus, dizziness, facial pain, arm pain, and migraine headaches. In the lower cervical spine (C3-C7), this can cause muscle spasms, crepitation, and/or paresthesia in addition to chronic neck pain. In either case, the presence of excessive motion between two adjacent cervical vertebrae and these associated symptoms is described as cervical instability. Therefore, we propose that in many cases of chronic neck pain, the cause may be underlying joint instability due to capsular ligament laxity. Currently, curative treatment options for this type of cervical instability are inconclusive and inadequate. Based on clinical studies and experience with patients who have visited our chronic pain clinic with complaints of chronic neck pain, we contend that prolotherapy offers a potentially curative treatment option for chronic neck pain related to capsular ligament laxity and underlying cervical instability.The Open Orthopaedics Journal 10/2014; 8(1):326-45. DOI:10.2174/1874325001408010326