Mechanisms of low back pain: a guide for diagnosis and therapy

Introduction

Low back pain (LBP) is the most common musculoskeletal condition affecting the adult population, with a prevalence of up to 84%¹. Chronic LBP (CLBP) is a chronic pain syndrome in the lower back region, lasting for at least 12 weeks². Many authors suggest defining chronic pain as pain that lasts beyond the expected period of healing, avoiding this close time criterion. This definition is very important, as it underlines the concept that CLBP has well-defined underlying pathological causes and that it is a disease, not a symptom. CLBP represents the leading cause of disability worldwide and is a major welfare and economic problem¹. Given this complexity, the diagnostic evaluation of patients with LBP can be very challenging and requires complex clinical decision-making. Answering the question, “what is the pain generator?” among the several structures potentially involved in CLBP is a key factor in the management of these patients, since a diagnosis not based on specific pain generator can lead to therapeutic mistakes. This article aims to provide a brief clinical guide that could help in the identification of pain generators through a careful anatomical description, thereby directing clinicians towards the correct diagnosis and therapeutic approach.

Low back pain epidemiology

LBP represents a major social and economic problem. The prevalence of CLBP is estimated to range from 15 to 45% in French healthcare workers³; the point prevalence of CLBP in US adults aged 20–69 years old was 13.1%⁴. The general population prevalence of CLBP is estimated to be 5.91% in Italy⁵. The prevalence of acute and CLBP in adults doubled in the last decade and continues to increase dramatically in the aging population, affecting both men and women in all ethnic groups⁶. LBP has a significant impact on functional capacity, as pain restricts occupational activities and is a major cause of absenteeism^7–9. Its economic burden is represented directly by the high costs of health care spending and indirectly by decreased productivity^7,9. These costs are expected to rise even more in the next few years. According to a 2006 review, the total costs associated with LBP in the United States exceed $100 billion per year, two-thirds of which are a result of lost wages and reduced productivity¹⁰.

Looking for the pain generator

LBP symptoms can derive from many potential anatomic sources, such as nerve roots, muscle, fascial structures, bones, joints, intervertebral discs (IVDs), and organs within the abdominal cavity. Moreover, symptoms can also spawn from aberrant neurological pain processing causing neuropathic LBP^11,12. The diagnostic evaluation of patients with LBP can be very challenging and requires complex clinical decision-making. Nevertheless, the identification of the source of the pain is of fundamental importance in determining the therapeutic approach¹³. Furthermore, during the clinical evaluation, a clinician has to consider that LBP can also be influenced by psychological factors, such as stress, depression, and/or anxiety^14,15. History should also include substance use exposure, detailed health history, work, habits, and psychosocial factors¹⁶. Clinical information is the leading element that drives the initial impression, while magnetic resonance imaging (MRI) should be considered only in the presence of clinical elements that are not definitely clear or in the presence of neurological deficits or other medical conditions¹⁷. The recommendation of the American College of Radiology is not to do imaging for LBP within the first 6 weeks unless red flags are present. They include recent substantial trauma or milder trauma in those over 50 years old, weight loss or fever with no known cause, immunosuppression, a previous cancer diagnosis, intravenous drug use, sustained corticosteroids use or osteoporosis, being over 70 years old, and focal neurologic deficit with progressive or disabling symptoms^18–20.

Imaging findings are weakly related to symptoms. In one cross-sectional study of asymptomatic persons aged 60 years or older, 36% had a herniated disc, 21% had spinal stenosis, and more than 90% had a degenerated or bulging disc²¹.

Although it is not possible to gauge accurately, it is easy to believe that these conditions could have a yearly cost, directly and indirectly, of more than $50 billion and conceivably up to $100 billion²². A recent study estimated that lumbar radiography was performed 66 million times in the United States in 2004, with a cost of $54 for each exam²³. Although estimates vary substantially depending on geographic location, insurance status, and other factors, costs of MRI seem to be 10 to 15 times higher^23,24.

The most recent guidelines for clinicians suggest that when faced with LBP patients, the clinician should go through a careful diagnosis of the mechanisms that sustain acute and/or chronic pain. Treatment has to be addressed specifically to these mechanisms. In this manner, we could avoid the common mistake of making the diagnosis of “simply low back pain”, resulting in improper treatment of a definition and not a complex disease. As chronic LBP could have simultaneous multiple pain generators, a multi-disciplinary diagnosis and multimodal treatment is necessary²⁵.

Anatomy of the low back

The lumbar spine consists of five vertebrae (L1–L5). The complex anatomy of the lumbar spine is a combination of these strong vertebrae, linked by joint capsules, ligaments, tendons, and muscles, with extensive innervation. The spine is designed to be strong, since it has to protect the spinal cord and spinal nerve roots. At the same time, it is highly flexible, providing for mobility in many different planes.

The mobility of the vertebral column is provided by the symphyseal joints between the vertebral bodies, with an IVD in between. The facet joints are located between and behind adjacent vertebrae, contributing to spine stability. They are found at every spinal level and provide about 20% of the torsional (twisting) stability in the neck and low back segments²⁶. Ligaments aid in joint stability during rest and movement, preventing injury from hyperextension and hyperflexion. The three main ligaments are the anterior longitudinal ligament (ALL), posterior longitudinal ligament (PLL), and ligamentum flavum (LF). The canal is bordered by vertebral bodies and discs anteriorly and by laminae and LF posteriorly. Both the ALL and PLL run the entire length of the spine, anteriorly and posteriorly, respectively. Laterally, spinal nerves and vessels come out from the intervertebral foramen. Beneath each lumbar vertebra, there is the corresponding foramen, from which spinal nerve roots exit. For example, the L1 neural foramina are located just below the L1 vertebra, from where the L1 nerve root exits.

IVDs are located between vertebrae. They are compressible structures able to distribute compressive loads through osmotic pressurization. In the IVD, the annulus fibrosus (AF), a concentric ring structure of organized lamellar collagen, surrounds the proteoglycan-rich inner nucleus pulposus (NP). Discs are avascular in adulthood, except for the periphery. At birth, the human disc has some vascular supply but these vessels soon recede, leaving the disc with little direct blood supply in the healthy adult²⁷. Hence, metabolic support of much of the IVD is dependent on the cartilaginous endplates adjacent to the vertebral body. A meningeal branch of the spinal nerve, better known as the recurrent sinuvertebral nerve, innervates the area around the disc space²⁸.

The lumbar spine is governed by four functional groups of muscles, split into extensors, flexors, lateral flexors, and rotators. The lumbar vertebrae are vascularized by lumbar arteries that originate in the aorta. Spinal branches of the lumbar arteries enter the intervertebral foramen at each level, dividing themselves into smaller anterior and posterior branches²⁹. The venous drainage parallels the arterial supply³⁰.

Typically, the end of the spinal cord forms the conus medullaris within the lumbar spinal canal at the lower margin of the L2 vertebra³¹. All lumbar spinal nerve roots stem from the connection between the dorsal or posterior (somatic sensory) root from the posterolateral aspect of the spinal cord and the ventral or anterior (somatic motor) root from the anterolateral aspect of the cord³¹. The roots then flow down through the spinal canal, developing into the cauda equina, before exiting as a single pair of spinal nerves at their respective intervertebral foramina. Cell bodies of the motor nerve fibers can be found in the ventral or anterior horns of the spinal cord, whereas those of the sensory nerve fibers are in the dorsal root ganglion (DRG) at each level. One or more recurrent meningeal branches, known as the sinuvertebral nerves, run out from the lumbar spinal nerves. The sinuvertebral nerve, or Luschka’s nerve, is a recurrent branch created from the merging of the grey ramus communicans (GRC) with a small branch coming from the proximal end of the anterior primary ramus of the spinal nerve. This polisegmentary mixed nerve directly re-enters the spinal canal and gives off ascending and descending anastomosing branches comprising both somatic and autonomic fibers for the posterolateral annulus, the posterior vertebral body and the periostium, and the ventral meninges^32,33. The sinuvertebral nerves connect with branches from radicular levels both above and below the point of entry, in addition to the contralateral side, meaning that localizing pain from involvement of these nerves is challenging³⁴. Also, the facet joints receive two-level innervation comprising somatic and autonomic components. The former convey a well-defined local pain, while the autonomic afferents transmit referred pain.

Pathophysiology of spinal pain

Pain is mediated by nociceptors, specialized peripheral sensory neurons that alert us to potentially damaging stimuli at the skin by transducing these stimuli into electrical signals that are relayed to higher brain centers³⁵. Nociceptors are pseudo-unipolar primary somatosensory neurons with their neuronal body located in the DRG. They are bifurcate axons: the peripheral branch innervates the skin and the central branches synapse on second-order neurons in the dorsal horn of the spinal cord³⁶. The second-order neurons project to the mesencephalon and thalamus, which in turn connect to somatosensory and anterior cingulate cortices in order to guide sensory-discriminative and affective-cognitive features of pain, respectively³⁷. The spinal dorsal horn is a major site of integration of somatosensory information and is composed of several interneuron populations forming descending inhibitory and facilitatory pathways, able to modulate the transmission of nociceptive signals³⁸. If the noxious stimulus persists, processes of peripheral and central sensitization can occur, converting pain from acute to chronic. Central sensitization is characterized by the increase in the excitability of neurons within the central nervous system, so that normal inputs begin to produce abnormal responses³⁷. It is responsible for tactile allodynia, that is pain evoked by light brushing of the skin, and for the spread of pain hypersensitivity beyond an area of tissue damage. Central sensitization occurs in a number of chronic pain disorders, such as temporomandibular disorders, LBP, osteoarthritis, fibromyalgia, headache, and lateral epicondylalgia³⁹. Despite improved knowledge of the processes leading to central sensitization, it is still difficult to treat^40,41. Peripheral and central sensitization have a key role in LBP chronification. In fact, minimal changes in posture could easily drive long-lasting inflammation in the joints, ligaments, and muscles involved in the stability of the low back column, contributing to both peripheral and central sensitization. Furthermore, joints, discs, and bone are richly innervated by A delta fibers whose continuous stimulation could easily contribute to central sensitization.

Type of spinal pain according to pain generator

In spite of the hard work done by the International Association for the Study of Pain⁴¹, there remains a degree of confusion in the medical community regarding the definitions of back pain, referred pain, radicular pain, and radiculopathy. Nevertheless, a precise diagnostic assessment is necessary to indicate the right treatment. An incorrect diagnosis and use of a therapy that is not appropriate could also be related to insufficient diagnostic skills of a non physician specialized in this syndrome, attributed to a clinical and/or instrumental analysis of insufficient depth, or a therapeuthic approach geared towards controlling the symptom (pain) rather than the pain generator mechanisms²⁵.

Mostly, LBP is considered to be nonspecific⁴², and the mistaken idea that the cause of 80 to 90% of LBP cases is unknown has persisted for decades^43–47.

Muscle tension and spasm are among the most common reasons for LBP, for example, in patients with fibromyalgia. In other cases, LBP can be attributed to different pain generators, with specific characteristics, such as radicular, facet joint, sacro-iliac, and discogenic pain, as well as spinal stenosis.

Discogenic pain

Disc degeneration (DD) has been estimated as the source of CLBP in 39% of cases⁸⁶. Its symptoms are aspecific, axial, and without radicular radiation and they occur in the absence of spinal deformity or instability. DD is often a diagnosis of exclusion among other types of CLBP. Pathologically, it is characterized by the degradation, within the disc, of the NP matrix with accompanying radial and/or concentric fissures in the AF⁸⁷.

Despite numerous recent advances, the main issue is how inflammation is initiated and sustained to lead to CLBP. A possible explanation could involve the growth of nerves capable of signaling pain deep into the annular structures⁸⁸. Another hypothesis involves a class of molecules, called damage-associated molecular patterns (DAMPs), including hyaluronic acid and fibronectin fragments, able to stimulate sterile inflammation of the disc through the action of pro-inflammatory cytokines (IL-1beta, IL-6, and IL-8) and matrix degrading enzymes (MMP-1, MMP-3, and MMP-13)⁸⁷. Also, subclinical anaerobic bacterial infection, encouraged by hypoxic conditions, could have a role in the development of discogenic pain⁸⁸.

Imaging MRI can detect changes in the endplates and in the vertebral bone marrow, such as edema in the vertebral bodies (Modic type 1). Clinical trials have demonstrated that some patients suffering from LBP have improvement following amoxicillin-clavulanate^88,89. Moreover, diabetes increases the risk of developing painful DD because advanced glycation end products (AGEs) induce catabolism and promote inflammation⁹⁰.

MRI cannot definitively demonstrate whether a disc is painful⁹¹. Provocation discography aims at reproducing patients’ pain through contrast injection during live fluoroscopy plus CT imaging for clarifying associated morphological abnormalities of the disc⁹². The clinical utility of discography and its diagnostic accuracy is, however, a matter of controversy because of poor specificity. Beyond the reported complications as discitis, neurologic injury, visceral injury, and dye reactions⁹³, it’s been demonstrated that the needle puncture of the lumbar disc may lead to accelerated MRI-documented DD. The mechanism is likely multifactorial: structural damage caused by the needle, pressurization, and toxicity of the contrast media⁹⁴.

Figure 1. MRI sagittal image showing an abnormal alignment of lumbar vertebrae; black discs (red arrow) are pathogenetic for discogenic pain; facet joint hypertrophy (yellow arrow) is pathogenetic for facet joint pain.

Figure 2. MRI axial image showing reduction in the size of the spinal canal (blue arrow), a pathogenetic finding in spinal stenosis; the red arrow shows radicular compression that can cause radicular pain.

Concluding remarks

LBP is one of the most common symptoms and conditions motivating individuals to seek medical consultation. The effects of back pain on society are significant, both epidemiologically and economically, and this is likely to only further increase owing to a combination of shifting attitudes and expectations, medical management techniques, and social provision.

Hence, LBP must always be addressed as a complex disease in which it is mandatory that an accurate diagnosis of pain generators is determined before starting any treatment. All the guidelines currently avalaible stress the importance of a multimodal and multidisciplinary approach in order to determine a strategy to solve the problem and not simply alleviate symptomatic pain. Finally, a careful follow up is important to adapt our therapeuthic strategies to dynamic clinical manifestations of CLBP.