Lumbar Degenerative Disc Disease: From Bench to Bedside

Back pain is second only to the common cold as a cause of lost time from work and results in more lost productivity than any other medical condition. Although being a common condition, the diagnosis of the pain generating structure and mechanism of pain generation remains to be completely understood. As the diagnosis is uncertain, so is the treatment. Traditional concepts for treatment of lumbar disc degeneration have aimed at symptomatic relief by removing the offending disc and limiting motion in the lumbar spine. Understanding the pathophysiological basis of disc degeneration is essential for the development of treatment strategies that target the underlying mechanisms of disc degeneration rather than the downstream symptom of pain. Researchers are working on novel treatment strategies which aim to induce disc regeneration or to replace the degenerated disc. These strategies involve stem cells, growth factors, and gene therapy. At present, treatment options for degenerative disc disease remain suboptimal, and the novel treatment strategies are not accepted as the standard of care. We are unable to morphologically differentiate between an aging and a degenerated disc. Explaining cause of pain in the absence of MRI findings is quite unsettling for the treating physician. On the other side we come across individuals with MRI showing severe degenerative changes with a patient with minimal discomfort. Like other degenerative diseases, genetic predisposition for Lumbar degenerative disc disease too should have a plausible explanation. These are some issues which need to be answered with a firm scientific conviction. The pathophysiology of pain mechanism is so complex that formulating treatment protocol eludes standardization. The type of pain in low back pain during the acute stage is nociceptive in character. It assumes central sensitization on becoming chronic. There occurs a functional reorganization within the pain matrix of the brain. A brief outline is provided of our present understanding of, the anatomical basis of pain mechanism based on the current, available body of literature. Literature search was carried out pertaining to low back pain within the last ten years. Experience of senior physicians treating low back pain was taken and conclusions were drawn. Keeping the current scenario in the back drop, it is proposed that since the cause of low back pain is multimodal, medical care providers should adopt a multi-disciplinary model in order to provide effective pain relief. The treatment modalities should include physical therapy, pharmacotherapy, interventional local pain modulating therapy and surgical intervention. Auctores Publishing – Volume1-10001 www.auctoresonline. org Page 01 Auctores Publishing – Volume1(1)-001 www.auctoresonline. org Page 02 Evolving concepts pain and treatment strategies Despite the inherent challenge in elucidating the specific etiology of chronic low back pain, diagnostic procedures can reveal its source in up to 90% of patients. De Palma et al elucidated that three principal joints contribute to stability of the spine. Amongst the three joint each has a share in contributing to pain . Seeing each joint in isolation it has been found that percentage distribution of each joint to pain for zygapophysial joints, sacroiliac joints, and lumbar discs are 31%, 18%, and 42%, respectively [1]. Crock was the first to propose that isolated internal disc disruption (IDD) without nerve root irritation could cause discogenic pain [2]. IDD can be found in 26%-42% patients of chronic low back pain [1, 3 &4]. Our current understanding believes IDD to be a distinct clinical entity which needs to be distinguished from other pain causing entities [5]. A recent study has classified discogenic low back pain into two types. They are annular disruption-induced low back pain (IAD) and internal endplate disruption (IED)-induced low back pain. These two distinct types have been fully supported by clinical and theoretical bases. Treatment of IAD is removal of the offending disc and that of IED is lumbar spinal fusion [6]. In addition to structural causes, psychosocial factors also play an important role in determining back pain behavior. Psychosocial factors are unlikely to predict as to who will experience back pain in the first place [7]. Recent studies have shown that low back pain seems to have a genetic correlation. As on date 40 genes have been found which are involved in development of Disc [8] . The aging process of disc follows a pattern of biochemical cascade. Am V. VO and colleagues proposed a biochemical cascade of disc aging by dividing it into three phases: (1) accumulation of damage to biomolecules, (2) aberrant cellular response to damage, and (3) loss of biologic structure and function [9]. Although a aged disc and degenerated disc has certain biochemical dissimilarities, studies have yet to prove any distinct dissimilarity in imaging morphology between an aged disc and a degenerated disc [10, 11]. Anatomy of low back pain Bogduk and Twomey have extensively described the innervation of spinal structures [12]The dorsal rami of each spinal nerve divides into three branches. Lateral branches supply the iliocostalis lumborum muscle and the skin; intermediate branches supply the longissimus muscle and the apophyseal joints. Medial branches supply the apophyseal joints, the interspinous and multifidus muscles, and also the interspinous ligament. Each medial branch supplies the apophyseal joints at its own level and also the joint below. Vertebral body endplates have the potential to be painful as they carry sensory innervation [13]. The posterior longitudinal ligament contains an extensive plexus of nerve fibers which also have free and encapsulated endings. [14] The grey rami communicantes arises from the lumbar sympathetic trunks to join the ventral rami of the lumbar spinal nerves thereby forming a mixed nerve called the sinuvertebral nerve. The sinuvertebral nerve supplies the posterior and posterolateral annulus fibrosus, and the posterior longitudinal ligament. De Palma and colleagues conducted studies on various pain sensitive structures and concluded that , zygapophysial joints, sacroiliac joints, and lumbar discs contributed to pain by 31%, 18%, and 42%, respectively[15] Biochemical Pain Sensitization There is growing evidence that pain arises from disrupted degenerated discs, but not from old dehydrated discs. However, even the most severe degenerative changes can sometimes be observed in people who have no back pain, suggesting that pain perception depends on biochemical / central pain sensitization mechanisms which are yet to be fully established [16] . It is also possible that some individuals with degenerated and narrowed discs do not experience pain as the load bearing is transferred to neural arch. Many patients reporting to the pain physician have an element of chronicity which implies that the pain mechanism has a nociceptive and central component. Central sensitization is defined as “ an amplification of neural signaling within the central nervous system (CNS) that elicits pain hypersensitivity” [17]. A key brain area implicated in pain neuromatrix is the amygdala. The amygdala along with the hippocampus and anterior cingulate cortex are implicated in the development of pain memories. The development of such a pain memory applies to all movements that once provoked pain. This results in protective behaviors (e.g. antalgic posture movement patterns, altered pelvic motor control and probably also, avoidance of particular movements like forward bending) [18]. Even preparing for such ‘dangerous’ movements can evoke activation of the fearmemory center in the brain thereby eliciting pain without any peripheral nociceptive input. This will also prompt the patient to adopt a protective motor control strategy [19] . Amongst all cases of low back pain only a subgroup develop central sensitization. The exact mechanism orchestrating the same is still a mystery. Pain Neurosciences have also revealed that Glial over activity and poor sleep may play an important role in central sensitization. [20, 21] . Contemporary pain Neurosciences aims at identifying the relevant pain mechanisms in a patient of chronic low back pain. Knowing these mechanisms will help the clinician m in devising appropriate physical therapy and postural exercises which will help in retraining the pain memories. Some of these interventions can also be directed towards targeting sleep disturbances. Aberrant neuro vascularization Branches of the sinuvertebral nerve, the spinal nerves, and gray rami communicants have been the targets for most pain intervention procedures. Studies have demonstrated painful discs to have increased proliferation of nerve fibers and blood vessels in the disc which is otherwise an aneural structure . Studies have shown a correlation between aberrant neuro vascularization and expression of neurotropins [22]. Studies suggest that an imbalance between the matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) results in dehydration of disc leading to buckling of the annular lamellae. This leads to increased focal segmental mobility and shear stress to the annular wall. Delamination and fissuring within the annulus can result. Annular delamination and annular fissuring are two separate and distinct events [21, 22&23]. These degenerative disc changes affect the normal external load bearing, predisposing patient to back strain, even within physiological limits of weight bearing and motion [25]. The degenerative disc and the degenerative painful disc have a subtle difference. Early degenerative changes encompass biochemical and metabolic changes with aging without any structural failure. The term degenerative disc disease is applied to a painful degenerative disc with structural failure which may include radial tear of the annulus fibrosus, herniated intervertebral disc,