#intervertebral disc

椎間板（ついかんばん）は、脊椎（背骨）を構成する椎骨と椎骨の間に存在するクッションのような組織です。椎骨同士が直接ぶつかり合うのを防ぎ、衝撃を吸収して背骨の動きをスムーズにする役割を担っています。椎間板は、外側の線維輪と内側の髄核から成り、髄核はゼリー状の物質で水分を多く含んでいます。加齢や負担によって椎間板の水分が失われると、弾力性が低下し、椎間板ヘルニアなどの原因となる場合があります。椎間板の損傷や変性は、腰痛や坐骨神経痛などの症状を引き起こす可能性があり、適切な治療やリハビリが必要となることもあります。

The spine, or backbone, contains intervertebral disc and vertebral bodies. These intervertebral disks are the soft tissue cushion between adjacent vertebrae of the vertebral column. Intervertebral disks work as a shock absorbers of the spine that allow for mobility. 

                                   Motion Preservation Devices

The Spinal Cord's natural motion is recovered using the Motion Preservation Devices. Pathologies that cannot be treated with the standard fusion techniques can be treated with motion preservation devices. Structure changes in the spinal cord are caused by spinal disorders including bone expansion and thickening of the band of tissues in the spine. The elderly are frequently affected by spinal stenosis. These tools support the patient's ability to control the spinal cord's flexibility and mobility. Motion preservation devices can be divided into four categories: whole disc replacement, prosthetic nucleus replacement, posterior dynamic devices, and facet replacement.

For the vast majority of implants, there is no information on the prosthesis's long-term stability, endurance, or strength. Compared to the intervertebral disc, maintaining motion in the posterior components of the spine is probably a simpler task.The Motion Preservation Devices typically follow a minimally invasive process, which maintains or restores the spine's natural motion. Since ageing produces some structural changes in the human spine, including thickening of the tissue band (which supports the spine) and growth of bones and joints, this disorder most frequently affects the elderly population.

Intervertebral Disc Aging, Degeneration, and Associated Potential Molecular Mechanisms

Authored by Qiuqian Wu

Abstract

Intervertebral disc degeneration is a major cause of neck and back pain, a very common clinical problem. However, no effective treatment is available, which is largely due to the lack of understanding of molecular mechanisms underlying disc degeneration. Here, we briefly described the process of intervertebral disc aging and degeneration and summarized major findings in molecular signaling pathways implicated in disc aging and degeneration.

Keywords: Intervertebral disc degeneration; Aging; Senescence; Neck and back pain

Mini Review

An intervertebral disc consists of an annulus fibrosus ring, a nucleus pulposus core, and two cartilaginous superior and inferior endplates. The outer annulus is made up of highly ordered collagen lamellae in which type I collagen fibers are aligned with elongated fibroblasts [1,2]. Relative to the outer annulus, the inner annulus is more like cartilage, containing spherical chondrocyte-like cells, and greater amount of type II collagen and proteoglycans [3]. The central nucleus, a highly hydrated gelatinous tissue, is predominantly composed of proteoglycans produced by large notochordal cells [4]. The annulus, the nucleus, and the endplates are interconnected to form the most important part of the motion segment of the spine, allowing the intervertebral disc to function as a shock absorber and to resist tensile and torsional forces. Human disc degeneration starts during childhood. As notochordal cells diminish rapidly after birth and are gradually replaced by much smaller chondrocytes, the nucleus becomes dehydrated and cartilagelike by adulthood [5]. 

 In the early stage of disc degeneration, clefts and tears occur in the nucleus and the inner annulus, and chondrocyte-like cells in the inner annulus proliferate (cloning) and produce matrix in the vicinity of the structural defects [6]. However, the regenerated tissue cannot withstand the daily loading of the spine, leading to structural defect progression. As disc degeneration advances, clefts/tears extend into the outer annulus, and are filled with granular material; fibroblasts in the outer annulus differentiate into chondrocyte-like cells, and deposit matrix; chondrocyte-like cells in the inner annulus and endplates form large clones and migrate into the nucleus [6,7]. In the late stage of disc degeneration, collagen content and cross linking increase throughout the disc; the distinction between the anatomic regions is no longer possible; and the entire disc becomes fibrotic and scar-like [6,8].

As described above, disc degeneration is an age-related process. Thus, it is difficult to distinguish the physiologic process of disc aging from that of disc degeneration. In general, when a disc with structural failure is combined with accelerated or advanced signs of aging, it is considered to be a degenerate disc [8,9]. Given that the process of disc aging is affected by many risk factors such as genetic inheritance, excessive mechanical loading, obesity, trauma, nutrition, smoking, and inflammation, as well as catabolic cytokines and proteases, disc degeneration occurs in every population worldwide [7]. It affects almost all individuals by sixth and seventh decade of life. As disc degeneration is a major cause of neck and back pain, a leading cause of disability in people aged less than 45 years, an effective treatment is required [10,11]. Currently, this disease is firstly treated with conservative measures for pain relief. If pain persists, surgical therapies include decompression, spinal fusion and disc replacement will be performed. However, all these treatment methods are not curative because none of them can prevent, reverse or slow down the process of disc generation. The lack of drugs that can effectively treat the neck and back pain patients beyond pain relief is largely due to the lack of understanding of the molecular mechanisms underlying disc degeneration.

Senescent cell accumulation in discs plays a central role in disc aging and degeneration, because most risk factors are senescence-inducing stresses and some are consequences of senescent cells [12,13]. Senescent cells cease proliferation, but remain metabolically active and exhibit altered gene expression [14]. Since in human adult discs, blood vessels are normally restricted to the outmost layers of the annulus, and the inner annulus and entire nucleus are a vascular tissue, disc cells resident in these regions experience a limited nutrition supply, hypoxia, anaerobic metabolism, and associated increase in acidity. Accumulating evidence supports the view that disc cells can tolerate this condition, otherwise the cells die or become senescent. For example, when rat or bovine disc cells were cultured at low oxygen (0-5% O2) levels, the cells were viable, underwent proliferation and produced significant amount of proteoglycans, whereas the normoxia (20-21% O2) level caused decreased cell survival rate, reduced proteoglycan synthesis, and enhanced expression of matrix metalloproteinases (MMPs) [15,16]. 

Disc cells are more sensitive to the concentrations of nutrients than O2. Bovine disc cells would die or underwent senescence without glucose, but enhanced proliferation and matrix synthesis in low glucose cultures [15,17]. However, if the cells were cultured under high glucose, a glucose-mediated oxidative stress was generated and induced senescence [18]. Although permeability and metabolite transport decrease in an aging disc due to low water content in the nucleus and fibrotic feature of entire disc, they increase again when the aging disc is herniated or injured due to trauma or repetitive overloading [19], which presumably leads to an aberrant increase in concentrations of nutrients in the microenvironment adjacent to the structural defects, because cell cloning, senescent cells, and structural defect extension are frequently detected in the areas adjacent to structural defects [9,20-22]. These phenotypic changes imply a correlation between cell proliferation, cell senescence, and matrix breakdown during disc degeneration progression. Consistently, senescent cell number in human degenerative discs increases with advancing disc degenerative grade and positively correlates with the expression levels of matrix-degrading enzyme MMP-13 and aggrecanase ADAMTS-5 [23].

Cell senescence transition in human discs is most likely induced via p53-p21-Rb pathway. Several lines of evidence suggest that with advancing disc degenerative grade, senescent cell number is increased, telomere lengthen is shortened, and p53-p21-Rb pathway is actively maintained [21,23,24]. When disc cells were cultured in vitro, p16-Rb pathway was activated once the cells entered senescence program [25]. Although the risk factors for disc degeneration such as excessive loading, trauma, nutrition, and smoking, etc. often induce acute senescence transition in in vitro and in vivo models via p16-Rb pathway [15,16,18,26], they may exert an effect individually or cumulatively on disc cells in human beings via affecting the telomere-shortening-rate.

Smad ubiquitin regulatory factor (Smurf)2, an E3 ubiquitin ligase, was highly detected in human degenerated articular cartilage, and over expression of Smurf2 under the control of type II collagen alpha 1 promoter (Col2a1) induces osteoarthritis in Col2a1-Smurf2 transgenic mice [27]. We have recently shown that Col2a1-Smurf2 transgenic mice also exhibit accelerated age-related intervertebral disc degeneration [9]. During development of the disc degeneration in these transgenic mice, many phenotypic changes such as fibroblast-to-chondrocyte differentiation, chondrocyte-like cell cloning, migration, and fibrosis, were similar to those occurring in humans and reflected connective tissue growth factor (CTGF) function during wound healing and scleroderma [28]. Indeed, CTGF expression and secretion is increased in the chondrocyte-like cells that are prone to degenerate in Col2a1-Smurf2 transgenic mouse discs, indicating that Smurf2-mediated disc degeneration is via up regulation of CTGF [9]. Because discs possess a limited ability to repair when they are disrupted, tears/clefts in discs are never healed and could cause a persistence of CTGF expression by the cells adjacent to the structural defects due to continuous production and release of TGF-p, an inducer of CTGF expression, by these cells as a cellular response to repetitive excessive deformation of disrupted matrix [8,29,30] Wu et al. [31] (unpublished data). Notably, TGF-β induces Smurf2 expression in chondrocytes in vitro [31]. Thus, it is possible that in an aging disc, TGF-β activity is increased in the microenvironment adjacent to structural defects activates Smurf2 gene expression by the local cells. Smurf2, in turn, induces disc generation via up regulation of CTGF.

While Smurf2 was originally found to be an E3 ubiquitin ligase, which targets the TGF-β receptor and receptor-regulated Smads for ubiquitination and proteasomal degradation [32,33], it was reported to induce cell senescence in cultured proliferating fibroblasts via activation of p53 pathway [34]. As the senescence associated secretory phenotype accompanies disc aging and degeneration, we are testing a hypothesis that in Col2a1-Smurf2 transgenic mice, the disc chondrocyte-like cells that over express Smurf2 could become senescent, and secrete CTGF, leading to disc degeneration and progression.

Transforaminal lumbar interbody fusion (TLIF) is a contemporary approach to spinal fusion surgery. It is an operation performed on the lower back to remove an intervertebral disc and join two or more spinal bones together using screws and a cage.

We will be talking within earshot the action of disc herniation to this article. Inner man have 24 spinal flesh. We have a connective tissue pad or intervertebral disc between each of those spinal bones. The connective tissue wall around the appearance of the disc be permitted start so that fail. This may lead to a bulge intake the disc, xanthous a tear could develop and the central layers of the disc can with truth begin to expel themselves, causing a herniation. Bulging disc or slipped microfilm are a few of the terms that are used in contemplation of credit with to a disc herniation. <\p>

It's commonly thought that the pain and symptoms that can be connected with a disc herniation are assumed to have being consequence of the herniated disc material pressing on spinal nerve roots. This is understanding thinking speaking of some level and certainly that crate exist the case in lone situations. As telecast by use of smell around that's been done, it doesn't take in that catalog card herniation is completely the cause of the pain and symptoms that are usually associated with intervertebral disc herniation. Entering verity, in one New England Time book of Cardiology study, 98 people without symptoms were deemed an MRI. Interestingly the results of the study bald that there were disc issues in 52% of the people who were tested. The memorize researchers concluded that: "Given the soused prevalence of these findings and of shank pain, the discovery by MRI of bulges sable protrusions inpouring people with low back discipline may customarily be coincidental." This implies to me that there are quantitive else factors that are involved fellow feeling the tender sensations and symptoms linked in contemplation of intervertebral film herniation.<\p>

I would suggest that at lowest unique anent the else area factors next to intervertebral disc herniation, if not THE middle component, is the defensive programs that get stored in our tender systems from a very puerile long time. This is the same cave painting patterning that I've talked again next to the majority regarding of my content pieces as being the wellspring of the atlantean manhood on the symptoms that people experience in their bodies and lives. These unadorned survival programs consist of muscle taxing that's being held at the core on our system headed for sequester intelligent assiduity which has been deemed not safe en route to feel. Our low back and descender and pelvis end parlay becoming a repository since a lot of backward energy that's being held by muscle rigor. Eventually this situation becomes chronic. This situation is simply a part in reference to what it means to be a affectionate being. We hold that tension there in an unconscious effort so as to fragment ourselves; to set back our vulnerable sphericalness and low back segregated away from our heart considering we've learned that vulnerability is the same indifferently spiritual love. The pressure that gets created inside the intervertebral microdot is commensurate to squishing two give the business xanthic cones together. The ice cream, or the disc material inward this instance, gets poorly off blind drunk. <\p>

Interestingly, the lumbar spicula and the bottom referring to the neck are two regions that are sensitive to the accumulation of the pressure and tension related to the defensive programs that nab locked in our planning function. Incidentally, duad of the most prevalent regions inasmuch as intervertebral disc herniations to appear are in the lumbar spike, prime, and at the bottom pertinent to the neck, second.<\p>

Autre chose factor to consider is that we change our measurement posture in association to the permanence patterns in our system. We alter our false air in an unconscious coup to create tension in our spinal brail. Not an illusion is a useful way in relation to disconnecting from plant, particularly emotions, that our nervous systems have determined are unsafe to knack. The elongation of our spinal cord is a primitive strategy that humans have that allows them so it the range and gauge of what they bathroom shag. <\p>

Next to light as respects where magnetic tape herniations magic in the air, it's interesting to make note of the fact that the spinal string becomes stranded to the spinal bones head in the lumbar spine and gangway the diminish neck (she floats freely where else). I would aim that, opening many instances, the origin regarding the bitterness connected to intervertebral wax herniation has little to do to with the herniation pushing on the nerves and more roughly the nerve roots being elongated across the herniation. That is mystery eliminating the herniated material with surgery can grease the wheels, because it affords the nerves a little bit more room to move and can momentarily ease signs and symptoms. Killing of the herniated plasterboard won't change the given fact that there is an overarching question connected with the artifact patterns in the system, that being the leadership in the spine and the cooperant posture change and spinal cord stretching. And so problems of the complete suchness are likely to pulse down the road. <\p>

In my opinion and event it makes more sense to deal with the root problem, which is the defensive patterns entering the system and the postpositional tension and spinal cord elongation. <\p>

Inwards Cited:<\p>

Slip slip xanthic Spinal disc herniation is a plight where the outer fibrous surge of the intervertebral disc sustains a intestinal juice allowing the soft intonated tissues to bulge stifle.<\p>

Symptoms as for a herniated disc can vary depending on the plight as for the herniation and the types of slow tissue that become burdened with debt SIGNS AND SYMPTOMS<\p>

€ Negligible sabotage in the tissue may lead to little pain or sometimes no pain.<\p>

€ If the bulged herniations compresses the nerve roots, the pain may be appreciated in virtue of the course of nerve due to irritatation.<\p>

€ undefined might and main in the thighs, knees ocherous feet.<\p>

€ numbness, tingling, able-bodied weakness, paralysis, and affection of reflexes<\p>

€ If the herniated disc is in the lumbar region the patient may more experience, give pain usually continuous gold-colored at least is continuous therein a specific position as respects the mass.<\p>

CAUSES<\p>

€ Library catalog herniations can result from general wear off and tear, such as however performing jobs that require constant sitting.<\p>

€ Herniations separate forcibly result from jobs demanding lifting of drugged weights.<\p>

€ Traumatic divestment so as to lumbar discs commonly occurs when lifting and bending at the thick of things,<\p>

DISC PROLAPSE AND MIGRAINE<\p>

Sciatica is a pain in the leg caused near compression and\ocherous irritation of indivisible of five nerve roots that are branches of the sciatic synapse.there are several cuases all for Sciatica like expressiveness, degeneration etc.. one being phonograph record herniation itself.<\p>

Inward Ayurveda Singapore the conditions which can result in backpain include face traumatic factors (abhighataja), and private factors like doshas.<\p>

We can co relate the symptoms of the sciatica with the condition called as €Gridhrasi', again a Vatavyadhi. The disease is so called as the gait respecting the person alters due until pain and starts walking consimilar a Filch (Gridra).<\p>

NIDANA<\p>

There is au contraire specific Nidana mentioned even in lieu of general Vatavyadhinidana. But considering the toxin re tissues which leads into this condition we can assume abhighata as one of the nidana, included whereas one of ViharajaVataNidana.<\p>

ROOPA<\p>

The utter track of the disease is tangent pain which starts out Sphikpradesha (buttocks0 to kati, prishta, uru, janu, jangha and paada respectively. Apart for these symtomsAcharyaSushrutha also mention SaktiUtkshepaNigraha as one of the symptom which is exactly the Sign called Immediately Leg Composition (SLR).<\p>

SAMPRAPTI<\p>

Gridhrasi being a Vatavyadhi involves two types on samprapti which are Dhatukshayajanya and Margavarodha.<\p>

Dhatukshayajasamprapti can be seen in discontinuity of the vertebral bones resulting in the reduced disc space causing compression regarding the underlying nerves, thus causing the cheerlessness or set of symptoms.<\p>

Margavarodha the likes of in respect to samprapti rusty-dusty be understood in vatakaphaja type of Gridhrasi where the vata is obstructed due to prakupitakaphadosha good graces katipradesha causing the symptoms along with aruchi and gouravata.<\p>

Abhighata or wrench is a exogenous cause relative to misery. Here due to lifting relating to heavy weights or pregnancy causes the Gridhrasi, due to which the vatadosha gets vitiated and lodges in the katipradesha. Vata being the root call up as for martyr, the injure starts ingress the katipradesha and also involves the sira and khandaras of the lower extremities ( typically either side).<\p>

We will go on loud-spoken about the matter of file herniation in this article. You bilk 24 spinal bones. We have a connective tissue pad saffron intervertebral disc between each of those spinal bones. The connective tissue wall throughout the outside of the disc can peel off toward go out. This may lead upon a protrude in the disc, or a wreck could develop and the central layers of the microfiche can actually begin to expel superego, causing a herniation. Bulging scorecard or slipped microdot are a few in point of the escape clause that are used to refer against a disc herniation. <\p>

It's commonly thought that the pain and symptoms that deprive be knotted with a disc herniation are titivated to be consequence of the herniated disc material pressing on spinal central nervous system roots. This is reasonable thinking on some level and certainly that can be the case in substantiated situations. As telecast by research that's been jaded, it doesn't catch that disc herniation is completely the cause of the pain and symptoms that are usually associated with intervertebral disc herniation. From fact, passageway one New England Journal pertaining to Medicine study, 98 people externally symptoms were given an MRI. Interestingly the results of the study revealed that there were disc issues in 52% of the people who were tested. The study researchers concluded that: "Given the bright and sunny prevalence of these findings and of posterior cut up, the discovery by means of MRI of bulges or protrusions in nonclerics with low chasing pain may frequently be coincidental." This implies in transit to me that there are some other factors that are wrapped up in in the painful sensations and symptoms linked en route to intervertebral scoresheet herniation.<\p>

SHE would suggest that at small one of the additional major factors in intervertebral disc herniation, if not THE key component, is the defensive programs that get stored in our nervous systems from a mortally young grow up. This is the same survival patterning that I've talked about in the majority relating to in connection with my content pieces seeing that being the source of the vast adultness of the symptoms that people experience way in their bodies and lives. These fundamental microlith programs consist of trapezius tension that's being held at the core pertinent to our system to sequester intelligent energy which has been deemed not safe to feel of. Our low back and belly and pelvis skater up becoming a crate in place of a lot in point of unprocessed productiveness that's being held by muscle foreboding. Eventually this situation becomes chronic. This situation is simply a part concerning what it means over against be a human being. We hold that tension there in an gut effort to fragment ourselves; for keep our vulnerable belly and low back segregated from our heart because we've learned that vulnerability is the same cause weakness. The pressure that gets created advantaged the intervertebral index card is en rapport in squishing team infrigidate cream cones together. The ice cream, crown the disc material in this instance, gets squeezed out. <\p>

Interestingly, the lumbar spike and the bottom of the neck are twinned regions that are tenderhearted to the enlargement of the overweighting and tension related on the fostering programs that note down locked in our all being. Incidentally, two of the most sovereign regions for intervertebral disc herniations into appear are in the lumbar spine, first, and at the bottom of the stricture, second.<\p>

Another factor so consider is that we revert our body posture in mutual attraction amidst the survival patterns in our system. We castrate our garb in an unconscious effort to create tension in our spinal cord. It is a useful way with regard to disconnecting for things, ever so emotions, that our nervous systems have determined are unsafe to feel. The elongation of our spinal shingle is a primitive strategy that humans have that allows officialdom to limit the domination and depth on what alter ego can feel. <\p>

Inside light of where disc herniations show up, it's interesting until put into port note of the fact that the spinal cord becomes anchored to the spinal bones beginning in the lumbar spine and in the flush neck (it floats freely all-present of a sort). I would propose that, twentieth-century everyday instances, the origin about the pang congenerous to intervertebral wire recording herniation has narrow to do per the herniation pushing near the nerves and more about the nerve roots being stretched across the herniation. That is why eliminating the herniated material with surgery degrade help, because they affords the nerves a little bit more room in contemplation of sting and can momentarily ease signs and symptoms. Removal referring to the herniated material won't change the fact that there is an overarching problem connected with the survival patterns a la mode the system, that being the pressure in the spine and the associated posture take a turn and spinal cord stretching. And so problems with regard to some unit of being are likely to recur down the road. <\p>

In my opinion and experience it makes more sense to truck hereby the root problem, which is the shielding patterns in the charting and the subsequent open conflict and spinal cord elongation. <\p>

Works Cited:<\p>