DEGENERATIVE DISCOGENIC SYNDROME

Therapeutic Considerations

- Introduction -

International Published Data

GMCD Instructional  Course Lectures

Author :  

Dr. med. Guy M.C. Declerck MD (GMCD)

Medical FRCS-, FRCS Ed Orth-, M Ch Orth-, PhD-studies

Spinal Surgical and Research Fellow, Perth, Western Australia

Spinal Orthopaedic Surgeon and Surgical Instructor

Consultant R&D Innovative & Restorative Spinal Technologies

President International Association of Andullation Technology (IAAT)

Translation: Filip Vanhaecke PhD

Illustrative expertise and page layout: Lennart Benoot, Mincko, Halle, Flanders, Belgium

Review scientific literature: Medical Consulting Advice, Ostend, Flanders, Belgium

Support: International Association of Andullation Therapy (IAAT)

Legal advice:  Anthony De Zutter, kornukopia.be

  www.guy-declerck.com

Dedication to my Mother (October 2015)

Mammy. Life was harsh to You. Economic crisis in the late 1930s, Second World War, left by my father, but continuing to work on your own to realise your two dreams: your piano and your son. No doubt You helped me to shape my future. Your humility, honesty and wisdom showed me how to persevere and withstand all difficulties in my life. When you marked my forehead with a cross and when you rubbed my face, it meant a lot to You: ‘Guy, never forget what I taught you. Deny those who criticize and betray you. And don’t worry if people lie to you. From then on you know that believing them won’t be possible anymore. I know, nobody and nothing will ever halt you. Soon or later you’ll be a happy man!’.

Acknowledgements

Relying on the work of giants is the lifeblood of scientific research. Indeed, if I have seen further, it is by standing on the shoulders of giants. One might even say that I have always depended on the kindness of strangers in this regard*. The continuous support by professor BA Kakulas (Neuropathology), professor JR Taylor (Spinal Anatomy and Human Biology), and Sir George M Bedbrook (Spinal Orthopaedic and Rehabilitation Surgeon) made it possible to analyse 27539 post-mortem human spines, normal and pathological, in the Department of Neuropathology, Royal Perth Hospital/University Western Australia, Perth.

Note: in order not to disturb easy reading of the underneath scientifically based chapters, only a few authors are mentioned in the text where dr. Guy considered it essential. Their names are placed between brackets. Further information on their individual research can be read in the last chapter ‘Literature Encyclopedia’.

(*) Mirsky Steve. Technology is making it harder for word thieves to earn outrageous fortunes. Scientific American, February 2014, p. 64

Contents

1. What to do in case of the well-known chronic non-lethal low back pain condition?

2. Why does research fail to develop a universally accepted therapeutic procedure?

3. An aging process can – as yet – not be treated.

4. Treatment of a painful degenerating lumbar IVD.

5. Which are the basic problems for finding a working biologic solution?

6. LBP and CLBP patients sense wishful thinking regarding therapies.

7. Scientific basis for whatever type of treatment.

8. Animal models for evaluation of innovative biological intradiscal therapies.

9. Pain as an incapacitating symptom.

10. Differences between acute LBP (ALBP) and chronic degenerative discogenic LBP (CLBP).

1. What to do in case of the well-known chronic non-lethal low back pain condition?

Although the lumbar intervertebral disc (degenerative or not) is commonly thought to be responsible for severe low back pain (and sometimes leg pain) and is the primary target for diagnostic and therapeutic interventions since 1934, a straight forward and generally accepted treatment for this type of painful disc pathology still not is available.

The progressing but irreversible degenerative and inflammatory changes inside the lumbar intervertebral discs (IVDs), which occur in approximately 80 % of all human individuals, form a large public health problem as they may be associated with episodes of terrible pain. Chronic low back pain (CLBP) related to this degenerative discogenic syndrome (DDS) ruins both life quality and labour capacity of the patient and increases the use of health services. Contrary to non-developed countries, in industrialised states this non-lethal CLBP condition is very commonly associated with long durations of sick leave, worker’s compensation claims, and litigation (Mannion).

But Weisz indicates that concern with chronic disease is hardly new, but that modern medicine and society yet have to provide human and effective solutions to the problem. Although an enormous amount of literature data is available regarding the cellular and molecular processes going on during the degenerative processes in the lumbar IVD, till now little effort has been made to relate this information and to provide a rationale for an appropriate and universally accepted treatment. Therefore, treating discogenic LBP still remains an exceptional therapeutic challenge (Battié).

The CLBP patient is asking for symptomatic therapy and pain relief. Whenever possible, the sufferer likes to be offered the most appropriate and specific therapy dealing with the underlying defect. But in addressing the underlying processes of IVD degeneration, for many patients neither conservative nor surgical management is effective at relieving their pains. However, even though in many instances physicians have no clue about the exact cause of the patient’s LBP, treatment modalities exist which are - temporarily - effective in either reducing pain or disability or both.

Proceeding with a particular treatment for CLBP due to the degenerative processes in the lumbar IVD is largely based on a huge amount of articles available in medical literature indicating that it works well in at least 30 patients. But it is essential to think critically about how science finds its way into the media. The scientific literature is impossibly vast. There are over 24,000 academic journals in existence and 1,3 million academic papers published every year. The media are all too eager to publicize even highly dubious claims. It remains therefore essential to emphasize the value of systematic reviews where the standards for including studies are clearly defined and strictly implemented. But this is extremely difficult. And not to forget ….. the governments as well ignore peer-reviewed research that questions the value of their pet policies (Goldacre).

The major peak for LBP associated with DDS is situated between 25 en 55 years. Thereafter, Nature takes care that the spine stiffens, becomes less mobile and less painful. Then, and much earlier in life, why not initiating and stimulating these natural healing processes which respect the normal course of Nature? However, when secondary consequences do develop (spondylolisthesis and spinal stenosis), more than satisfactory surgical procedures exist to resolve their signs and symptoms.

Indeed, the existing treatments in dealing with DDS are currently limited to ameliorating symptoms and pain. Current treatments for lumbar disc degeneration fall into two categories. Conservative and nonsurgical management entails analgesics, rehabilitation programs, and lifestyle adjustments such as weight loss (Slade). Surgical intervention involves spinal fusion and disc arthroplasty (Yang).

But till now, none of all these hundreds of varying therapies has proven to respect the natural history of the normal aging and degenerating lumbar spine. None of them neutralises the degenerative processes in the different structures of the IVD. And therefore, none of these therapies will be able to provide an universally efficient and long-lasting good or excellent result (more than 5 to 10 years). None is superior to Nature’s own course. And if thought otherwise, let’s continue to try! The author is convinced that 'there's no need for fiction in medicine for the facts will always beat anything you fancy (Doyle)’.

The desire to find an innovative method dealing directly with the mechanisms by which pain originates and is produced, is old and hasn’t changed over the last decades. Only the technology has improved. Unfortunately, till now there exists no clinically proven biological therapy for neutralising the degenerative intradiscal processes using biologically active molecules.

Does restoration of the lumbar IVD function really constitutes the ultimate goal? It seems acceptable that if the loss of annular disc height and the loss of normal intervertebral flexibility can be ‘restored’, further degenerative intervertebral hypermobility, degenerative spondylolisthesis, and degenerative spinal stenosis can be prevented.

But will research finally overthrow Nature’s own course? While continuously experiencing the natural laws of aging and degeneration, the author wouldn’t mind losing some of his IVD functions and IVD ROM as long as he does not become a CLBP patient. And as most flexion happens at the level of the hips, would he feel a difference? Till now he has no choice but to accept the fate of Nature’s evolution in his body: overall loss of water and therefore becoming more rigid in his intervertebral joints without pain.

The succeeding chapters are based on an intensive review of thousands of medical articles related to the IVD and discussions with a lot of IVD-interested colleagues over the last 30 years. The author remains convinced that one day neutralisation or possibly regeneration of the degenerative processes into the IVD will be able to decrease the pain due to the degenerative discogenic syndrome which occurs in over 80 % of all human beings.

2. Why does research fail to develop a universally accepted therapeutic procedure?

The enormous (chronic) LBP crisis still awaits an exact explanation and a universally accepted solution. As long as all steps in the degenerative processes of the lumbar IVD have not been discovered and interrelated, it still will take some time to develop an appropriate treatment. In the meantime, only non-scientifically proven treatments will continue to be offered in an attempt to settle LBP.

Research hasn’t failed but till now wasn’t able to provide sufficient answers for developing an universally accepted therapeutic solution for CLBP of degenerative discogenic origin. In order to develop such a treatment, it remains essential to fully understand all combined mechanisms in the origin and production of pain. CLBP is multifactorial. It relates to the combined interferences of genetic inheritance, aging processes, nutritional IVD problems, and mechanical factors causing the degenerative and inflammatory responses in the lumbar IVD. As for today, only resolving the biomechanical aspects of the degenerating discogenic problem never will succeed in suppressing LBP.

That an objective anatomic diagnosis must precede rational treatment of CLBP seems intuitive. But till now (2015), this still remains impossible. Roentgenograms, CATs, MRIs, joint injections, and discographies reveal a wealth of anatomic and pathological details which all are part of the normal aging processes. The major problem is that these abnormalities are present as well in individuals who do not suffer LBP and are encountered in nearly all autopsy specimen (Jensen; Benneker).

Where, then, is the pain coming from? Strangely enough, some medical and paramedical trained individuals are able ‘to see pain’ on radiological images! On the contrary, the author never encountered somebody who could see pain! This might change in the future once an equivalent of the Clarity-scan will emerge to evidence cellular and molecular changes related to pain (Karl Deisseroth). Unless the specific and potentially pain producing structural abnormalities in the endplate and/or in the annulus fibrosus cannot be exactly identified, the huge variety of conservative and surgical treatments, not directly dealing with these functional deficits, will continue to be effective in only a very small percentage of CLBP sufferers.

Biochemists and engineers analysing the lumbar IVD are gradually finding their way in the complex aetiology of the aging and degenerative discogenic processes. Insights in the complex relationships between biology and mechanics of the IVD (spinal mechanobiology) hopefully will lead to full understanding and development of innovative and effective cause-related biologic treatments. Accurate non-invasive diagnostic tools will then be developed. Sooner or later medical and paramedical personnel will be taught in the anatomical and chemical abnormalities leading them to think in a rational and scientific based pattern as to provide evidence-based patient management.

3. An aging process can – as yet – not be treated.

In the normal course of aging, the IVD and in particular its nucleus pulposus (NP) undergo extensive cellular and chemical changes altering their morphology. The NP hardens and is transformed from a turgid gel of proteoglycans into a more desiccated fibrocartilaginous structure that appears similar to the inner annulus (Herzog). As the NP decreases its structural integrity, the IVD loses its flexibility as a whole. The normal course of these aging processes remains painless.

While the IVD ages, its biochemical processes progressively change the extracellular matrix structure (see chapter ‘Intervertebral Disc: Cells and Extracellular Matrix’). All notochordal cells will disappear. The NP cells proliferate less, become more senescent, undergo necrosis (= unregulated accidental cell death) or apoptosis (= regulated cell death). The disc pH (~ pH 6,3) decreases as a result of lactic acid accumulation (~ anaerobic glycolysis off the NP cells). The production of glycosaminoglycans and proteoglycans (especially aggrecan) decreases resulting in attracting and binding less water. Degradative enzymes such as cathepsins, aggrecanases, ADAMTS-4, and matrix metalloproteinases (various MMPs, collagenases, gelatinases, and stromelysins) appear in greater quantity. The concentration of tissue-inhibitors-of-MMPs (TIMPs) decreases leading to a further increase of the MMPS activity. Elevated levels of a variety of proinflammatory cytokines appear (tumor necrosis factor-α (TNF-α), IL-1α, IL-1β, IL-6, IL-8, IL-17) (Bibby; Burke; Horner; Ishihara; Johnson; LeMaitre; Lotz; Mwale; Ohshima; Razaq; Shamji; Tsuji; Urban).

Therefore, the aging-related morphological changes in the matrix of the NP cannot heal spontaneously. Moreover, the NP is avascular. Its nutritional metabolic transport becomes more and more compromised once sclerosis of the endplates occurs. The total absence of notochordal cells and low chondrocytic-like cell density in the NP do not allow a spontaneous repair of the matrix which, at the same time, remains constantly subjected to the daily mechanical loads.

4. Treatment of a painful degenerating lumbar IVD.

Degeneration is not the acceleration of the aging process.

Lumbar IVDs deteriorate over many years from the NP outwards and to an extent that is influenced by genetic inheritance and metabolite transport. The normal age-related deterioration can be accelerated by physical disruption during the normal daily loading activities and professional duties, which may lead the IVD to degenerate and even create a herniating pathway.

When the IVD further ages over an 80-year span and does not develop a radial and/or annular tear, no significant decrease in the MR signal intensity occurs. However, once such a tear in the IVD has developed, a decreased T2W MRI signal intensity starts being seen indicating the presence of degenerating IVD processes. Indeed, the occurrence of a radial and/or an annular tear is the most significant change in the IVD which may lead to full degeneration of the IVD.

Degenerative structural defects in the outer annulus and in the endplate (fissures and tears) heal by the formation of granulation tissue progressing inwards in the direction of the degenerating and degenerative NP. This healing process is due to a much higher cell density, better vascularisation, and greater nutrient supply. However, the healing granulation tissue may be invaded by blood vessels and pain sensitive nerves. This situation probably is one of the reasons why signs and symptoms of DDS may occur intermittently or even continuously when the degenerative IVDs no longer are able to be loaded in an homogenous way (Mulholland).

Degenerative annular tears most often affect the lower L4-5 and L5-S1 lumbar IVDs while degenerative tears in the endplate more often occur in the lumbar L1-L2 and L2-L3 IVDs. The lesions often become painful because the pain sensitive nerves in the peripheral annulus or vertebral endplates can be sensitised by inflammatory-like changes arising from contact with blood or displaced NP fragments. Indeed, surgically-removed human IVDs show an active inflammatory process proceeding from the outside-in. Animal studies confirm that effective healing occurs only in the outer annulus and in the endplates where cell density and metabolite transport are greatest. Healing of the peripheral IVD structures has the potential to relieve discogenic pain by re-establishing a physical barrier between NP and nerves, and reducing inflammation (Adams, Stefanakis, Dolan).

5. Which are the basic problems for finding a working biologic solution?

Although it remains an extremely difficult objective, there is little doubt that the clinical management of the patient with degenerative discogenic LBP will be distinctly different in 10 years’ time. One day, the whole process of lumbar IVD degeneration and the generation of degenerative discogenic pain will be understood in full detail so that reliable innovative biological treatments for DDS will be developed.

The major aim of these approaches will be the annihilation of LBP by neutralising the degenerative and inflammatory processes in the IVD. But there is still a long way to go before a genetically induced, cell induced, molecular induced, or engineered nuclear tissue will be developed which can be implanted securely inside the IVD without any risk of its extrusion.

What are some of the problems to find biologic solutions?

. IVD is an avascular structure,

. IVD is a harsh environment (acidic, low O2 tension, low glucose concentration),

. endplate changes occur overtime (insufficient nutrient supply),

. transport of metabolites through endplates becomes a major problem and limits cell reduplication,

. nuclear notochordal cells which maintain the extracellular matrix disappear,

. IVD has a low cellularity,

. altered cellular phenotypes appear,

. cell senescence, apoptosis and necrosis progress,

. adult cell density decreases in NP and AF,

. mRNA expression by NP cells decreases,

. normal present cells can’t repair their own disc structure,

. gene expression of cells changes,

. synthesis of proteoglycans and especially aggrecan declines,

. hydrostatic pressure falls,

. present aggrecans degrade,

. concentrations of small proteoglycans increase,

. production of collagen type II declines,

. synthesis of fibrotic collagens type I and III increase,

. disc profilometry indicates an abnormal mechanical environment,

. varying daily loading patterns continuously cause irreversible  structural changes and stimulate the

  biochemical degrading processes in the disc tissues,

. local mechanical damage leads to very high abnormal stress distributions leading to cell death,

. degradative enzymes (MMPs) appear,

. a variety of proinflammatory cytokines appear.

In the author’s opinion, the potential of future biological therapies as sole therapies will remain insufficient because the mechanical loading patterns on the IVD need to be stabilised as well.

6. LBP and CLBP patients sense wishful thinking regarding therapies.

Till now, therapies for degenerative discogenic LBP have been uniquely empirical and aimed at relieving symptoms rather than addressing the underlying degenerative disease mechanisms. The continuously increasing burden of LBP and the patient’s experiences prove that the existing therapeutic methods only have limited success.

Many patients obviously become angered because they cannot understand why the majority of medical and paramedical community lacks basic knowledge of an organic explanation for their chronic degenerative discogenic LBP.

Non-medically trained people have absolutely no idea and rarely any knowledge of how their spines and IVDs are structured and function. They mostly have no idea how the spine looks like and even are unable to design an image of a spinal column. To paraphrase Wilson Churchill, for the majority of people, the spine and the IVD remain a riddle wrapped in a mystery inside an enigma. Their misconceptions are even more nurtured by diagnostic terms without any sense such as ‘slipped disc’, ‘disc arthrosis’, ‘osteophytes’, ‘primary facet syndromes’, etc ... . Without understanding the mechanisms of the aging and degenerating processes in the lumbar IVD, it simply is impossible to explain the natural - and benign - history of chronic LBP related to the DDS (Bortz; Engel; Naliboff; Philips; Sterbach; Szasz; Waddell; Zarkowska).

Not every LBP patient will stoically accept that the cause of pain needs to be sought ‘in the mind and not in the back’. Most patients remain unimpressed by the usual hypotheses and theories of pain and psychological mechanisms, so complex that therapists don’t seem to understand themselves and get lost in their own explanations. Patients who are well educated, have rational professional functions and realistic expectations, find it unacceptable that a non-lethal condition will continuously interfere with their normal life style and responsibilities. They do not accept - and rightly so - that therapists do not take their pain seriously and are unwilling to treat their LBP more invasively because of all sorts of irrational self-imposed beliefs and restrictions.

Western societies in the early 21st century become characterised by people’s increasing disillusionment with scientific medicine (Deborah Lupton). Chronic LBP patients become more and more self-advocated because of lack of basic knowledge by the therapists regarding the potentially pain producing degenerative structural defects which occur as well as a consequence of the daily loading patterns on the aging IVD. As long as irrational and unsuccessful treatments continue to be performed and developed without the definite aim to neutralise the pain generated by degenerative discogenic defects (endplate fissures and complete annular tears) in a biological manner, whatever type of failed treatment will reinforce and aggravate pain, distress, illness behavior, and disability.

Complementary to their personality and beliefs, CLBP patients take their own responsibility to select potential pain relieving and ‘healing’ therapies such as nutrition supplements, yoga, herbal medicine, Chinese acupuncture, chiropraxy, fitness exercises, spinal manipulations etc. And why not?

Nevertheless, the chronic pain will finally progress to an inability of the chronic LBP sufferer to perform the usual daily tasks, to work, exercise, socialise and to sleep.

All kind of failed treatments, which finally may end in a despair treatment in the Pain Clinic (with a whole armamentarium as well) are the reasons why LBP patients end up developing emotional distress, depression, loss of self-esteem, isolation, and adoption of a sick role. All of these have been described as typical psychological consequences of chronic LBP. Indeed, despite the aid of all kinds of medical and paramedical interferences, chronic pain will induce an chronic illness behaviour that increasingly becomes dissociated from its original physical basis. Chronic pain may finally become a self-sustaining condition that is resistant to all traditionally known therapeutic managements and this occurs at all levels of society in the industrialised world.

7. Scientific basis for whatever type of treatment.

The goal of any (innovative) therapeutic procedure is addressing the known pain generator. But to develop and evaluate the efficacy and efficiency of (new) spinal (surgical) treatment strategies, it is essential to first understand the normal aging evolution of the lumbar IVDs, their biology and their biomechanics (see topics ‘Intervertebral Disc Extracellular Matrix and Biomechanical Function’). And it doesn’t seem to be very easy!

It still will take some time before intensive research, by understanding and respecting Nature’s course of the degenerative processes in the aging lumbar IVD, will lead to a biological method to (1) easily deal with the pain caused by inappropriate mechanical loading of the degenerative fissures, tears, and ruptures in the NP, the cartilaginous endplates and the AF, and to (2) annihilate and neutralise the underlying degrading and inflammatory processes (e.g. cytokines, TNF-alpha, NO). Therefore, and as long as the interaction of biochemistry and biomechanics (= mechanobiology) for causing LBP is not fully understood, CLBP will remain the albatross of industry (Pope).

In the author’s opinion, every therapeutic method must be evaluated against the following basic questions: (1) what causes the problem, (2) what is the natural history of the diagnosis, (3) is the diagnosis well defined by accurate tests, and (4) has the provided treatment proven to be effective?

Only long-term follow-up evaluation studies - minimum 10 years - are able to evaluate correctly the efficiency of an (innovative) therapeutic approach. This can be done by (very costly) randomized controlled trials (RCTs) which are performed on a small amount of patients (1.000 patients in the best case). However, the results of these studies rarely reflect situations in real-life circumstances because the individuals are extremely well screened before being allowed to participate. In other words, there usually exists a selective preselection. Although double-blinded, the results are not at all universally accepted. Much cheaper and much more efficient analyses are the comparative efficiency studies (CERs), digitally performed on over 100.000 patients. In CERs, different therapies are compared to each other in patients who are not preselected and continue to live their normal lives.

8. Animal models for evaluation of innovative biological intradiscal therapies.

Elaborating innovative and more efficient biological therapies targeting molecular and cellular components for neutralising the degenerative processes in the lumbar IVD first need animal models. However, none of the existing animal models mimics the human IVD. None can exactly replicate the integrated influence of biochemical and biomechanical effects (= mechanobiology) as occurs in the human degenerating IVD.

In vitro cell culture systems and small animals, such as rats and rabbits, are useful for screening the efficacy and safety of a new therapy. Ultimately, large animals such as goats and minipigs are required for assessing the effectivity and motivating the clinical use of such an innovative approach in humans (Beckstein).

But because it is not feasible to perform lumbar IVD biopsies in the human species, typical success metrics include measures of morphology (e.g. disc height, annular delamination, and disc degeneration grade via histology and MRI), cellularity, matrix quality/quantity, cytokine levels, and biomechanics (e.g., compressive strength, pressure/volume testing, and range of motion) (Masuda).

9. Pain as an incapacitating symptom.

For all practical purposes and in the absence of neural compromise - which is the case in the degenerative discogenic syndrome - pain remains the principal incapacitating symptom of lumbar intervertebral discogenic dysfunction caused by the degenerative process.

As is often the case, in therapeutic discussions regarding the pain, psychological and non-medical factors longer attracted attention than research into pure technologic solutions.

Today, recent diagnostic and therapeutic advances call for a new paradigm based upon methods that affect the fundamental evolution of the degenerative processes into the IVD. Only through new strategies of this nature may one hope to substantially improve the therapeutic results, which admittedly remain less than satisfactory overall.

10. Differences between acute and chronic degenerative discogenic LBP.

Chronic degenerative discogenic low back pain (CLBP) becomes a completely different clinical entity (= degenerative discogenic syndrome or DDS) from the experience of an acute low back pain attack (ALBP).

Benign ALBP with its typical and universal acute psychological anxiety and acute disability is proportionate to the obtained details related to the provoking event or activity. Medication, short period of limited activity, and physiotherapy are generally highly effective in settling an acute pain phase.

If the acute phase does not subside and/or if CLBP develops, the pain will have a significant negative impact on the quality of life for the sufferers and their immediate environment. CLBP sufferers continually seek to get relieved from their pains, they’ll change doctors and therapies regularly. But to no avail!

Literature Encyclopaedia

I refer to the separate chapter

Degenerative Discogenic Syndrome. Therapeutic Considerations. Literature Encyclopaedia