9/16/2020 FICCOResearch Enhanced Reader F1oo0Recearch 2016, 51000 Fac Roy) 1890 Last updated: 17 JUL 2018 REVIEW Mechanisms of low back pai [version 1; peer review: 3 approved] @ check or updates a guide for diagnosis and therapy Massimo Allegri, Silvana Montella’, Fabiana Salici’, Adriana Valente”, Maurizio Marchesini2, Christian Compagnone?, Marco Baciarello2, Maria Elena Manferdini2, Guido Fanellit:2 ‘Department of Surgical Sciences, University of Parma, Parma, aly 2anaesthesia, Intensive Care and Pain Therany Service, Azienda Ospedalera Universitaria Parma Hospital, Parma, aly V1_Fitst published: 28 Jun 2016, (1000 Faculty Rev:1530( Intpsdol.org0. 12688111 000research 8108.1) Latest published: 11 Oct 2016, (1000 Faculty Rev):1530 ( hitpsdoi.org0.12688171000reaearch 8105.2), Abstract Chronic iow back pain (CLBP) is a chronic pain syndrome inthe lower back region, lasting for atleast 3 months. CLBP represents the second leading cause of disability worldwide being a major weltare and economic problem. ‘The prevalence of CLBP in adults has increased more than 100% in the last decade and continues to increase dramatically in the aging population, affecting both men and women in all ethnic groups, witha significant impact (on functional capacity and occupational activities. It can also be influenced by psychological factors, such as strass, depression andlor anxiety. Given this complexity, the diagnostic evaluation of patients with CLBP can be very challenging and requires complex clinical decision-making. Answering the question “whats the pain generator” among the several structures potentially involved in CLBP is a key factor in the management of these patients, since a mis-diagnosis can generate therapeutical mistakes. ‘Traditionally, the notion that the etiology of 80% to 90% of LBP cases is tunknown has been mistaken perpetuated across decades. In most cases, low back pain can be attributed to specific pain generator, with its own characteristics and with efferent therapeutical opportunity. Here we discuss about radicular pain, facet Join pain, sacro-iliac pain, pain related to lumbar stenosis, discogenic pain, Our aticle aims to offer to the clinicians a simple guidance to identily pain generators in a safer and faster way, relying a Correct diagnosis and further therapeutical approach, Keywords low back pain, CLBP, back, spine Open Peer Review Reviewer Status ¥ ¥ v Invited Reviewers 1 2 3 ao v v v version 2 versiont v ¥ 1000 Faculy Reviews are written by members of the prestigious F1000 Faculty. They are commissioned and are peer reviewed betore publication to ensure thatthe final, published version is comprehensive and accessible, The reviewers ‘who approved the final version ae listed with their names and ations 4 Dino Samartzi, The University of Hong Keng, ‘Queen Mary Hospital, Pok Fu Lam, Hong Kong 22, Mark Schumacher, UCSF Schoo! of Medicine, San Francica, USA. 13, Christopher Gharibo, NYU Langone Medical ‘Center, New York, USA Any comments on the article canbe found at the ond ofthe arte chrome-extension://dagemkpagilhakfdhnbomgmidpkdkiffienhanced-reader.htm|2openApp&pdf... Paget 10 11109/16/2020 Enhanced Reader FICCOResearch FrocaResearch 2016, 1000 Facvty Rev)1590 Last updated: 17 JUL 2019 Corresponding author: Massimo leg (mallcriparmanesthesia com) ‘Competing intoroste: Massimo Alogi ha (Grunenthal Munipharma, Angel, CareFusin, and MSD, {Grant information: This work has boon euppoted by a FP7 Collaborative Project grant rom the European Community (PairOmics — ‘Muti<émensional OMICS approach to satiation o patents with lw back pan) grant agreement no: 6027266, Petts unresticted use, stbuton, and reproduction in any medium, provided the orignal wok is propery cited How to cite this article: Aeg M,MontlaS, Sais F otal Mechanisms of low back pan: guide for diagnosis and therapy [version 1: jeer review:3 approved) F000Research 2016, (1000 Facuity Rev1890 (ripe or 10 1258811 000researen 8105") Fret published: 28 Jun 2016, 51000 Faculty Rev):1590(htps/do xg 125881000re2enrch 8105.1) vod reeoarch fans and payment for speeches trom the flowing companies (nthe lst 2 years) Copyright: © 2016 Alogi Mota Ths isan open access ail dstributed undo the ts othe Croatve Commons Atrbton Lies, wich Pege2at 10 chrome-extension://dagemkpagilhakfdhnbomgmidpkdkiffienhanced-reader.htm|2openApp&pdf... 21109/16/2020 Introduction Low back pain (LBP) is the most common musculoskeletal eondi- tion affecting the adult population, witha prevalence of upto 84°" (Chronic LBP (CLBP) isa chronic pain syndrome inthe lower hack region, listing for at least 12 weeks’, Many authors suggest defin- ing chronic pain as pain that lasts beyond the expected period of healing, avoiding this close time cvterion, This definition is very important, as it underlines the concept that CLEP has well-defined underlying pathological causes and that it is a disewse, not a symptom. CLBP represents the leading cause of disailty world- ‘wide and is a major welfare and economic problem. Given this complexity, the diagnostic evaluation of patents with LBP can be very challenging and requires complex clinical decision-making Answering the question, “what isthe pain generator?” among the several structures potentially involved in CLBP is a key factor in the management of these patients, since a mis-diagnosis can lead to therapeutic mistakes. This article aims to provide a brief clni- cal guide that could help in the identification of pain generators ‘through a careful anatomical description, thereby directing elni- cans towards the correct diagnosis and therapeutic approach. Low back pain epidemiology LLBP represents 2 major social and economie problem. The prevae lence of CLBP is estimated to range from 15 to 45% in French healtheare workers’: the point prevalence of CLEP in US adults aged 20-69 years old was 13.1%, The general populstion preva- [ence of CLBP is estimated to he $.914 in aly The prevalence of acute and CLBP in adults doubled in the last decade and continues tw increase dramatically inthe aging population, affecting both men and women in all ethnic groups’. LBP has a significant impact on Functional capacity, as pain resriets occupational activities and isa ahsenteeism™. Is economic burden is represented dliwcly by the high cosis of health care spending and indizectly by decreased productivity”. These costs are expected to rise even more in the next few years. According to a 2006 review, the total ‘costs associated with LBP inthe United States exceed $100 billion per year, two-thirds of which area result of lst wages and reduced productivity”, Looking for the pain generator LBP symptoms ean derive from many potential anatomic sources, such as nerve roots, muscle, fascial structures, bones, joints, intervertebral dies (IVDs) and organs within the abdominal eavity Moreover, symptoms ean also spawn from aberrant neurological pain processing eausing neuropathic LBP!” The diagnostic evalu- ation of patents with LBP can be very challenging and requires complex clinical decision-making. Nevertheles, the idenitica- tion of the source of the pain is of fundamental importance in detenmining the therapeutic approach’. Furthermore, during the clinical evaluation, a elnician has to consider that LBP can also be influenced by psychological factors, such as stress, depres- sion, and/or anxiety"*", History should also include substance use exposure, detailed health history, work, habits, and psycho= social factors. Clinical information is the Teading element that dives the initial impression, while magnetic resonance imaging (MRI) should be considered only in the presence of clinical el ments that ae not definitely clear or in the presence of neurolog! call deficits oF other medical conditions”. The recommendation chrome-extension: //dagemkpagilhakfdhnbomgmidpkdkiffienhanced-reader.htm|2openAppapd... Enhanced Reader FoooResoach 2016, 81000 Faculty Ro-1S80 Lact updated: 17 JUL 2019 fof the American College of Radiology is not to do imaging for LBP within the frst 6 weeks unless red flags are present They include recent significant trauma of milder trauma at age older than 50 years, unexplained weight loss, unexplained fever, Jmmuaosuppression, history of cancer, intravenous drug use prolonged use of corticosteroids oF osteoporosis, age older than “70 years, and focal neurologic deficit with progressive or disabling Imaging findings are weakly related to symptoms. In one cross sectional study of asymptomatic persons aged 60 years or older, 368% had a heeniated disc, 21% had spinal stenosis, and more than 90% had a devenerated or bulging disc™. Although a precise estimate is impossible, itis plausible thatthe direct medical and indirect costs of these conditions are in the range of more than $50 billion per annum and could be as high 2s '$100 billion at the extreme. A recent study estimated that lumbar radiography was performed 66 million times inthe United States jn 2004, with a cost of $54 for each exam”. Although estimates, ‘vary substantially depending on geographic location, insurance status, and other factors, costs of MRI seem to be 10 t0 15 times higher" Consensus guidelines forthe management of LBP recommend that, the clinician use contemporary best practice for assessment and treatment and, if chronic, use a multimodal and multi-tiseipinary approach to avoid mis-diagnosis and mis-management Anatomy of the low back ‘The lumbar spine consists of five vertebrae (L1-L), The complex. tunalomy of the lumbar spine is & combination of these strong Yer- tebrae, linked by joint capsules, ligaments, tendons, and muscles, with extensive innervation. The spine is designed to be strong. since thas to protect the spinal eord and spinal nerve roots. At the same time, i is highly flexible, providing for mobility in many ditferent, planes. The mobility of the vertebral column is provided by the symphy- sel joints between the vertebral hodies, with an TVD 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 segments, Ligaments ad in joint stability dur ing est and movement. preventing injury from hyperextension and hyperlexion. The three main ligaments are the anterior longitu- nt (ALL), posterior longitudinal ligament (PLL), and flayum (LF). The canal is bordered by vertebral bod jes and dises anteriorly and by laminae and LF posteriorly. Both the ALL and PLL run the entire length ofthe spine, anteriorly and Posterior, respectively Lateral spinal nerves and vessels come fut from the intervertebral foramen. Beneath each lumbar vertebra, there is the comesponding foramen, fom which spinal nerve roots exit, Fr example, the L1 neural foramina ae located just below the LL vertebra, from where the L1 nerve root exits. IVDs awe located between vertebrae. They are compressible structures able to distribute compressive loads through osmotic Page Set 10 3/109/16/2020 pressurization, Inthe TVD, the annulus fbeosus (AF), 8 concentsic fing structure of organized lamellar collagen, susrounds the protcoglycan-rich inner nucleus pulposus (NP), Dises are avascular in adulthood, except forthe periphery. AC birt, the human disc has some vascular supply but these vessels soon recede, leaving the disc ‘with litle direct blood supply in the healthy adult®. Hence, meta- bolic support of much ofthe IVD is dependent om the cartilaginous endplates adjacent to the vertebral body. A meningeal branch of ‘the spinal nerve, better known asthe recurrent sinuvertebal nerve, innervate the afea around the dis space” “The lumbar spine is governed by four functional groups of ‘muscles, split into extensors, exer lateral Mexors and rotator. ‘The lumbar vertebrae are vascularized by lumbar arteries that ‘originate in the aorta. Spinal branches ofthe lumbar arteries enter the intervertebral foramen at each level, dividing themselves into simaller anterior and posterior branches". The venous drainage parallels the arterial supply", ‘Typically, the end of the spinal cord forms the conus medulla- tis within the lumbar spinal eanal at the lower margin of the L2 vertebra, All uma spinal nerve roots stem ftom the connection between the dorsal or posterior (somatic sensory) root from the posterolateral aspect ofthe spinal cord and the ventral or anterior (Somatic motor) root from the anterolateral aspect of the cord”. The ‘0018 then flow dawn through the spinal canal, developing into the ccauda equina, before exiting as single pairof spinal nerves at their respective intervertebral foramina. Cell bodies of the motor nerve fibers can be found in the ventral oF anterior horns of the spinal ‘cord, whereas those of the sensory nerve fibers are in the dorsal root ganglion (DRG) at each level. One of more recurrent menin= ‘geal branches, known as the sinuvertebral nerves run ou fom the Tumbar spinal nerves. The sinuvertebeal nerve, or Luschka's nerve, isa recurrent branch created from the merging of the grey ramus communieans (GRC) with a small branch coming from the proximal end of the anterior primary ramus of the spinal nerve. “This polisogmentary mixed nerve drelyte-entes the spins] canal and gives off ascending and descending anastomosing branches comprising hoth somatic and autonomic fibers forthe pesterola- teral annulus, the posterior vertebral body and the periostium, and the ventral meninges", The sinuvertebral nerves connect with ‘branches from radicular levels both above and below the point of dition to the contralateral side, meaning that localizing pain from involvement of these nerves is challenging”. Also, the Facet joints recoive two-level innervation comprising somatic and autonomic components. The former coavey a well-defined local ‘ain, while the autonomic afferents transmit referred pain Pathophysiology of spinal pain Pain is mediated by nociceptors, specialized peripheral sensory neurons that ale us to potentially damaging stimuli at the skin by transducing these stimuli into electrical signals that are relayed to higher brain centers. Nociveptors are pseudo-unipolar primary somatosensory neurons with their neuronal body located in the DRG. They are bifureate axons: the peripheral branch innecvates, the skin and the central branches synapse on second-order neurons in the dorsal horn of the spinal cord™, The second-order neurons Project to the mesencephalon and thalamus, which project t0 chrome-extension: //dagemkpagilhakfdhnbomgmidpkdkiffienhanced-reader.htm|2openAppapd... Enhanced Reader FoooResoach 2016, 81000 Faculty Ro-1S80 Lact updated: 17 JUL 2019 somatosensory and anterior cingulate cortices 0 drive sensory- discriminative and afective-cognitive aspects of pain, respectively. The spinal darsal hor is a major site of integration of somatosen- sory information and is composed of several interneuron popula tions forming descending inhibitory and facilitatory pathways, able to modulate the transmission of nociceptive signals. Ifthe noxious, stimulus persists, processes of peripheral and central sensitization can oceur, converting pain from aeute 1 chronic. Central sensitiz- tion is characterized by the inerease inthe excitability of neurons ‘within the central nervous system, so that normal inputs begin to produce abnormal responses", Iis responsible for tactile allodynia, {hat is pain evoked by light brushing of the skin, and for the spread ‘of pain hypersensitivity beyond an area of tissue damage, Central sensitization oecurs in a number of chronic pain disorders, such 2s emporomandibular disorders, LBP. osteoarthritis, fibromyalgia, headache, and lateral epicondylalgia”. Despite improved knowl edge of the processes leading to central sensitization its stil d= ficult. reat™™. Peripheral and central sensitization have a key role jin LBP chronification. In fact, minimal changes in posture could easly deve long-lasting inflammation inthe joins, ligaments, and ‘muscles involved in the stability ofthe low back column, contrib tuting to both peripheral and central sensitization. Furthermore, joints, discs, and bone are richly innervated by A delta fers ‘whose continuous stimulation could easly contribute to central sensitization ‘Type of spinal pain according to pain generator In spite of the hard work done by the Intemational Assocation forthe Study of Pain”. there remains a degree of confusion inthe ‘medical community regarding the definitions of hack pain, referred pain, radicular pain, and radiculopathy. Nevertheless, a precise diagnostic assessment is necessary to indicate the Fight treatment Misdiagnosis and mis-management of CLBP can also be influ enced by other considerations, such as insufficient knowledge or appreciation of the common sructure for speci pain referral pattems, inadequate clinical reasoning, unsuitable referal, and a preference for popular management approaches. Mostly, LBP is con- sidered to be nonspecific™, and the mistaken idea that the eause of 80 t0 90% of LBP cases is unknown bus persisted for decades. “Musele tension and spasm are among the most common reasons {or LBP, for example, in patients with fbeomyalgia, In ater eases, LRP can be attributed to different pain generators, with specific characteristics, such as radicular, facet joint, sacroiiae, and disco genic pain, as well 3s spinal stenosis. Radicular pain Radiculae pain is pain evoked by ectopic discharges emanating from an inflamed of lesioned dorsal root or its ganglion: gener- ally, the pain radiates from the back and buttock into the leg in 1 dermatomal distribution. Disc hemiation is the most com- ‘mon cause, and inflammation of the affected nerve rather than its compression is the most common pathophysiological px ess. Radicular pain is pain iradiated along the nerve root without neurological impairment. Even though itis nociceptive pain, it is distinguished from usual nociception because ia radicular pain the axons ace aot stimulated along their course o in thei peripheral terminals but from the perinevrium®*, Radicular pain ders from, Page 4ot 10 4/109/16/2020 radiculopathy in several aspects. Radiculopathy is a neurological state in which conduction is impaired along a spinal nerve or its roots. When sensory fibers are impaired numbness is the main symptom and siga, whereas when motor fibers are blocked weak= ‘ness ensues, Diminished reflexes can occur as a result of either ‘sensory oF motor block. The numbness is dermatomal in distribu- tion and the weakness is myotomal. Although radiculopathy and radicular pain often accompany one another, radiculopathy has ‘been observed in the absence of pain, and radicular pain may hap- ppen inthe absence of radiculopathy". tis important to undertine tha, contrary to popular belief cs not possible to make a distine- tion among the patterns of 4, LS, and SI radicular pain. la fact ‘only when radiculopathy is seen together with radicuae pain can ‘segments he estimated. In such eases, the dermatomal distribution ‘of numbness indicates the segment of origin rater than the disti- bution of pain, Lumbar dise herniation with radiculopathy can be diagnosed during clinica examination using manual muscle testing, supine staigh leg raise, Laségue sign, and crossed Laségue sign. 1 a patient's history and physical examination findings indicate lumbar dise herniation with radiculopathy, the most suitable non invasive test to confirm this could be an MRI. This is particularly important if itis necessary to proceed with an invasive treatment ‘to better define the neurological impairment, The next most appropriate test evaluate the presence of lumbar dise hemiation is computed tomography (CT) or CT myelography, which would be suitable for those individuals unable to have an MRI because its contraindicated or those for whom MRI is inconclusive, Also, diagnosis of nerve root compression may be achieved by elecrodi- agnostic studies, although they are notable to distinguish between lumbar dise herniation and other causes of nerve foot compres- sion, Unfortunately, we have to remark that radiculopathy could be present without radicular pain and vice versa. For these rea sons, electrodiagnostic tests are not recommended 8 first-line ‘approach but only’ as a second-line one in order to detine if there is ‘concomitant presence of peripheral neuropathy or neuralgia or to follow up the impairment ofthe lesioned nerve Facet joint syndrome “The lumbar zygapophyseal joints are the posterior articular ‘process of the lumbar column, They are Formed from the inferior process of upper vertebra and the superior articular process of lower vertebm. They are supplied by the medial branches of the dorsal rami (MBN). These joints have a large amount of free and ‘encapsulated nerve endings that aetivate nociceptive afferents and that are also modulated by sympathetic efferent fibers”. Lumbar _zysapophyseal or “facet” joint pain has heen estimated to account for up 10 30% of CLBP eases", with nociception originating inthe ‘synovial membrane, hyaline cartilage, bone, oF fibrous capsule of the facet joint Diagnosis of facet joint syndrome is often difficult and requires 3 careful clinical assessment and an accurate analysis of tadiological ‘exams, Patients usually complain of LBP with or without somatic referral to the legs terminating above the knee, often radiating to the thigh or to the groin, There is no radicular pattern. Back pain tends to be off-center and the pain intensity is worse than the leg Pain; pain increases with hyperextension, rotation, lateral bending. and walking uphill. It is exacerbated when waking. up from bed chrome-extension: //dagemkpagilhakfdhnbomgmidpkdkiffienhanced-reader.htm|2openAppapd... Enhanced Reader FoooResoach 2016, 81000 Faculty Ro-1S80 Lact updated: 17 JUL 2019 or tying to stand after prolonged sitting. Finally, patients often ‘complain of back slfines, which is typically more evident inthe rmoming'®". Jackson identified seven factors significantly cor- related with facet pain: older age, previous history of LBP, formal gait, maximal pain with lumbar extension, absence of leg pain, absence of muscle spasm, and absence of exacerbation with, Valsalva maneuver" There are no pathognomonic radiological findings fr the diagno sis of lumbar Facet syndrome. With MRI, we can find non-specific Signs of arthrosis,osteophytes, and hypertophy of fava ligaments, However, if we want to better study anthrosis problems, CT is, the prefered imaging method, even if radiation exposure should be Kept in mind™. One of the most important exams is provided by Xerays, especially dynamic projections, that can show col- ‘umn instability (isthesis that could be increased with flexion and extension ofthe low hack column) with a clear overload of these joints In conclusion, despite the contribution from neuroimaging, history and clinical examination remain fundamental steps in the diagnosis of facet join syndromes, Sacroiliac joint pain The sacroiliac joint (SUs) are highly specialized joimts that permit, sable (yet flexible) suppor tothe upper body”. Sacral movement involves the SUs and also directly influences the dises and most, likely the higher lumbar joints as wel, Is innervation is still not ‘well known; innervation by branches from the ventral lumhopel- vie sami has been reported but not verified, Conversely, ianervar tion ofthe SLI by small branches fom the posterior rami has been reported hy numerous authors. In 2012, Patel er al reported successful attenuation of SU pain sing neurotomy ofthe LS dorsal, primary ramus und lateral branches ofthe dorsal sacral rami from, SI to $3. Hence, there is sufficient evidence that this procedure has an important value for establishing diagnosis and prognosis The SU is well recognized as a source of pain in many patients, who present with CLBP%™. Theories of pain generation include Tigamentous o¢ capsular tension, extraneous compression or shear forees, hypomobility or hypermobility. aberrant joint mechanics, and imbalances in the myofascial of kinetic chain that result in inflammation and pain. Inta-atcular sources of SLI pain include osteoarthritis: extraarticular sources include enthesisligamentous, sprain and primary enthesopathy. tn addition, ligamentous, tendi- rows, or fascial attachment and other cumulative soft tissue iu Fies that may oeeur posterior to the dorsal aspect of the SLI may be n source of discomfort. In physical examination, its important to examine the movement of the joint, for example with stess test, consisting of pressing down on the iliac crest (pelvis) or upper thigh, which may reproduce the patient's pain SU pain is often underdiagnosed. It has o be considered in every Situation in which the patent complains of postural LBP that wors- en in siting postion and with postural changes. Furthermore, itis possible that SUI pain is often strictly related to facet joint, syndiomes as both are related to postural problems Finally, it is important to consider that SU pain could also be a sign of rheumatic disease. MRI findings of articular effusion and inflam ‘mation (especially if bilateral) can alert the clinician to consider this condition, Page Set 10 5/109/16/2020 Enhanced Reader 2016, 1000 Faulty Fev890 Last update: 17 JUL 2019 Black Disc Possible discogenic pain Facet Joint Hypertophy Possible facet pain Figure 1. MAI sagital 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, Spinal stenosis Possible spinal stenosis pain Disc herniation Possible radicular pain Figure 2. MRI axial mage showing reduction inthe size of the spinal canal (blue arrow), @ pathogenetic finding in spinal stenosis; the rod arrow shows radicular compression that can cause radicular pain. Lumbar spinal stenosis the diameter of the normal lumbar spinal canal varies from 15 10 Lumbar spinal stonosis (LSS) ean be congenital” or acquired (or 27 mm, We can define lumbar stenosis as a spinal canal diameter both). I could be determined by inflammatory/scar tissue after of ess than 10 mm, even though a stenosis with diamerer of 12 mam spine surgery or, even in absence of previous surgery. by dise her= of less in some patients can be symptomatic. The normal fram niation, thickening ofthe ligaments, or hypertrophy of the articular nl height varies from 20 to 23 mum, with the indicator of pot processes. The majority of eases of LSS are degenerative, related ial framinal stenosis us 15 mm of less". Degenerative LSS isthe in the spine with aging”. LSS is determined by a pro- most commoa indication for spinal surgery’ in people older than ofthe central spinal canal nd the lateral ecesses 65 years of age. The most frequent symptoms of lumbar stenosis nidiine back pain, radiculopathy with neurologic claudication, Page Set 10 chrome-extension://dagemkpagilhakfdhnbomgmidpkdkiffienhanced-reader.htmI?openAppapdf... 6/109/16/2020 ‘motor weakness, paresthesia, and impairment of sensory nerves” Symptoms may have a different distribution depending on the type of LSS. If the LSS is central there may be involvement of the area hetween the facet joint, and pain may be bilateral in a non-dermatomal distribution, With lateral recess stenosis, syimp= toms are usually found dermatomally because specific nerves ate ‘compressed, resembling unilateral radiculopathy”, Pain improves With trunk flexion, siting. stooping. or lying and aggravates with prolonged standing or lumbar extension, As the condition ‘becomes more advanced, siting or Tying down are less helpful in relieving the pain. In severe cases, rest pain or & neurogenic blad- der can develop", Neurogenic claudieation pain is the classical ‘ympiom of LSS. caused by venous congestion and hypertension ‘around nerve roots. Pain is exacerbated by standing erect andy downbill ambulation but alleviated with Iyiag supine more than prone, siting, squatting. and lumbar Nexion*”. LSS is generally diagnosed based on a combination of history. physical examination, and imaging”. The most useful findings from the history are age, radiating leg pain tha i exacerbated by standing up or walking, andthe absence of pain when seated. The ‘gait and posture after walking may reveal a positive “stoop test, performed by asking the patent to walk briskly. As the pain inten sifles, patients may complain of sensory symptoms followed by motor symptoms, and if they assume a stooped posture, symptoms may improve™. If patients sit in chair bent forward, they may Ihave the same rele” ‘The recommended method for confirming the diagnosis of LSS is MRI. which facilitates the assessment of the spinal eanal and the anatomic rlationship between spinal and neural elements™. The natural course of untreated LSS is unclear. The Neh American ‘Spine Society (NASS) clinical guidelines concluded thatthe natu- ‘al course is favorable ina thid to a half of patients with clinically mild to moderate LSS", Other reviews suggest thatthe condition may deteriorate in some patients and improve in about a third of ‘thers, with most patients remaining unchanged for up to 8 years of follow-up™ Discogenic pain Dise degeneration (DD) has been estimated as the source of CLBP. in 39% of cases", IIs symptoms are specific, axial, and without ‘radicular radiation and they eccurin the absence of spinal deformity ‘or instability. DD is often a diagnosis of exclusion among other types of CLBP. Pathotogicaly, it is characterized by the degrada~ tion, within the disc, of the NP matrix with accompanying radial andlor concent fissures in the AF® Despite numerous recent advances, the main issue is how inflam= ration is initisted and sustsined to lead to CLEP. A possible explanation could involve the growth of nerves capable of signaling ‘ain deep into the annular structures. Another hypothesis involves class of molecules, called damage-associated molecular pattems (DAMPS), including hyaluronic acid and flbronectin fragments chrome-extension: //dagemkpagilhakfdhnbomgmidpkdkiffienhanced-reader.htm|2openAppapd... Enhanced Reader FoooResoach 2016, 81000 Faculty Ro-1S80 Lact updated: 17 JUL 2019 able 10 stimulate sterile inflammation of che dise through the action of pro-inflammatory cytokines (IL-Ibeta, IL-6, and IL-8) sand matrix degrading enzymes (MMP-1, MMP-3, and MMP-13)°. Also, subclinical anserebic hacterial infection, encouraged by hypoxic conditions, could have a role in the development of Aiscogenie pain Imaging MRI can detect changes in the endplates and in the ver- tebral bone marrow, such as edema inthe vertebral bodies (Modic type 1). Clinical trials have demonstrated that some patients, suffering from LBP have improvement following amoxicilin- clavulanate™, Moreover, diabetes increases the risk of developing Painful DD because advanced glycation end products (AGES) catabolism and promote inflammation™. induc MRI cannot definitively demonstrate whether a disc is painful”. Provocation discography aims at reproducing patients’ pain through contrast injection during live fuorascopy plus CT imaging for clarifying associsted morphological abnormalities of the dise™. The clinical utility of discography and its diagnostic accuracy is, however, a matter of controversy because of poor specificity Beyond the reported complications as disctis, neurologic injury. visceral injury, and dye reactions®, i's been demonstrated thatthe needle puncture ofthe lumbar dise may lead wo aecelerated MRI- documented DD. The mechanism is likely multifactorial: steuetural damage caused by the needle, pressurization, and toxicity of the contrast media. Concluding remarks LBP is one of the most common symptoms and conditions moti- vating individuals to seek medical consultation. The effects of bck pain on society are significant, hoth epidemiologically and economically, and this is likely to only further increase owing to a combination of shifing sttiudes and expectations, medical ‘management techniques, and social provision. Therapeutical "approaches, including interventional modalities, for LBP are highly effective when used properly after a careful diagnostic work-up. Consensus guidelines for the management of LBP advise contem- Porary best practice for assessment and treatment and the use of a ‘ultimodal and muli-cisciplinary approach to avoid mis-diagnoss and mis-management in chronic cases Competing interests Massimo Allegri has received research funds and payment for speeches from the following companies (in the Tast 2 years): Gruneathal, Mundipharma, Angelini, CareFusion, and MSD. Grant information This work has been supported by a FPT Collaborative Projet grant from the European Community (PainOmies ~ Multi-dimensional OMICS approach to stratification of patients with low back pain) grant agreement no: 6027366 Page 7 of 10 7109/16/2020 References Enhanced Reader FoooResoach 2016, 81000 Faculty Ro-1S80 Lact updated: 17 JUL 2019 100 remanded 1 et it et pa 2 eprom atggrtPhem egein Sn sorasremaratas Ss RRA eee + Bowen tarps terme reper eh done oncaedtaly rpita ae 8 SSSI A SEE RS © BASSES Nace ft and Meson Esato Survey 208-297, drt a Ree toto) 2 ed At |Past F109 Recommendation 15 Apu Lo, Mae D The epidemiology senomie burden and iaacsigeivesman ocho iw bck pin Fane, Germany, ay Span and th UX'a ote Sued oven pert On Pwmacaer 208 sou) ase, Pith Abotact |Publoor ul Txt 6. Frtrer Hees Gl Agate Ro: Te Hing perience ol bone ow Fedora [Pusher Fue re Pa Tot 7 Danan, Teso AC, Hlman Stes reconenendtons rhe {ssoranant and managomert low back pan om ooo sn paves hcl Spa 207 108) st Fie Abstoct Pubs Pul Text 8. Dato Gere 52 van Den Loa: Low back Thr 23 a ASP Ped Abo |Pubaer ul Te Fee Fu Text 2. Prades Pee Piedepia Pra wrienc-baved intel rtm ‘ialnes on eaeiedshanieton treason ron bapa Pvt Fer 208 bay terre Pie Abunet Riu Abcsa utieter ited 11 Sra eC Shes Aa: Machanane-bsad ces of Iressa pal: ata sympa adage of al erstanion Neiienianeene nS Fated Rantect|PubimerFofon|FesPuttes 12, Taneitan x sober Pe 1 Th trent diagnos low bck fers on be sovig pas woo Pied Abst |Pubisher FT F100 Recommendation Beceem tinge ae aS ayes BOLE teat Roan 18, Tllooyo Ra yan b. Comsiock BA, a a Trajectories of symptoms and ‘Rtn lat son ow ac cats Spe eee) Ss ‘Pied act | Paber Full et 1009 Recommend lid Absa Fee ule! 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Sp 2018 a) 270, ites Abert |Puokshr Fa Tot F100 Feommendtin Page at 10 chrome-extension://dagemkpagilhakfdhnbomgmidpkdkiffienhanced-reader.htmI?openAppapdf... 9/109/16/2020 Enhanced Reader FIOCOResearch FrocoRecearch 2016, 5(F1000 Facuty Rev) 1830 Lact updated: 17 JUL 2019 Open Peer Review Current Peer Review Status: “¥ Yo ¥ Editorial Note on the Review Process F 1000 Faculty Reviews are written by members of the prestigious F000 Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. The reviewers who approved this article are: cn 1 Christopher Gharibo NYU Langone Medical Center, New York, NY, USA Competing Interests: No competing interests were disclosed, 2 Mark Schumacher UCSF School of Medicine, San Francisco, CA, USA Competing Interests: No competing interests were disclosed, 9 Dino Samartzis Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, Pokfulam, Hong Kong Competing Interests: No competing interests were disclosed, ‘The benefits of publishing with F1000Research © Your article is published within days, with no editorial bias © You can publish traditional articles, null/negative results, case reports, data notes and more © The peer review process is transparent and collaborative © Your article is indexed in PubMed after passing peer review © Dedicated customer support at every stage For pre-submission enquiries, contact research@t1000.com FICOOResearch chrome-extension://dagemkpagilhakfdhnbomgmidpkdkiffienhanced-reader.htmI?openApp&pd... 10/10