[Evidence-based interventions to treat chronic low back pain: treatment selection for a personalized medicine approach : German version]. / Evidenzbasierte Interventionen zur Behandlung von chronischem Schmerz im unteren Rücken ­ Therapieauswahl für einen personalisierten Behandlungsansatz : Deutsche Fassung.

INTRODUCTION: Chronic low back pain (cLBP) is highly prevalent in the United States and globally, resulting in functional impairment and lowered quality of life. While many treatments are available for cLBP, clinicians have little information about which specific treatment(s) will work best for individual patients or subgroups of patients. The Back Pain Research Consortium, part of the National Institutes of Health Helping to End Addiction Long-termSM (HEAL) Initiative, will conduct a collaborative clinical trial, which seeks to develop a personalized medicine algorithm to optimize patient and provider treatment selection for patients with cLBP. OBJECTIVE: The primary objective of this article is to provide an update on evidence-based cLBP interventions and describe the process of reviewing and selecting interventions for inclusion in the clinical trial. METHODS: A working group of cLBP experts reviewed and selected interventions for inclusion in the clinical trial. The primary evaluation measures were strength of evidence and magnitude of treatment effect. When available in the literature, duration of effect, onset time, carryover effect, multimodal efficacy, responder subgroups, and evidence for the mechanism of treatment effect or biomarkers were considered. CONCLUSION: The working group selected 4 leading, evidence-based treatments for cLBP to be tested in the clinical trial and for use in routine clinical treatment. These treatments include (1) duloxetine, (2) acceptance and commitment therapy, (3) a classification-based exercise and manual therapy intervention, and (4) a self-management approach. These interventions each had a moderate to high level of evidence to support a therapeutic effect and were from different therapeutic classes.

Evidence-based interventions to treat chronic low back pain: treatment selection for a personalized medicine approach.

Introduction: Chronic low back pain (cLBP) is highly prevalent in the United States and globally, resulting in functional impairment and lowered quality of life. While many treatments are available for cLBP, clinicians have little information about which specific treatment(s) will work best for individual patients or subgroups of patients. The Back Pain Research Consortium, part of the National Institutes of Health Helping to End Addiction Long-termSM (HEAL) Initiative, will conduct a collaborative clinical trial, which seeks to develop a personalized medicine algorithm to optimize patient and provider treatment selection for patients with cLBP. Objective: The primary objective of this article is to provide an update on evidence-based cLBP interventions and describe the process of reviewing and selecting interventions for inclusion in the clinical trial. Methods: A working group of cLBP experts reviewed and selected interventions for inclusion in the clinical trial. The primary evaluation measures were strength of evidence and magnitude of treatment effect. When available in the literature, duration of effect, onset time, carryover effect, multimodal efficacy, responder subgroups, and evidence for the mechanism of treatment effect or biomarkers were considered. Conclusion: The working group selected 4 leading, evidence-based treatments for cLBP to be tested in the clinical trial and for use in routine clinical treatment. These treatments include (1) duloxetine, (2) acceptance and commitment therapy, (3) a classification-based exercise and manual therapy intervention, and (4) a self-management approach. These interventions each had a moderate to high level of evidence to support a therapeutic effect and were from different therapeutic classes.

Spatial distribution of fat infiltration within the paraspinal muscles: implications for chronic low back pain.

PURPOSE: Fat infiltration (FI) of the paraspinal muscles (PSMs) measured using MRI is an aspect of muscle quality and is considered to be worse in chronic low back pain (cLBP) patients. However, there is not a clear association between paraspinal muscle FI and cLBP, leaving the clinical importance of paraspinal muscle composition unestablished. The spatial distribution of FI in the PSMs may inform mechanistic understanding of non-specific cLBP as it relates to degenerative intervertebral disc (IVD) pathology. We hypothesized that paraspinal muscle fat-mapping would reveal distinct FI distribution patterns in relation to cLBP symptoms and proximity to symptomatic IVD degeneration. METHODS: From advanced-sequence water-fat MRI of 40 axial cLBP patients and 21 controls, we examined the spatial distribution of paraspinal muscle FI in relation to the center of rotation at the L4L5 disc. Using statistical parametric mapping, we compared FI patterns for multifidus (MF), erector spinae (ES), and psoas between patients and controls, and to the presence and severity of adjacent degenerative IVD pathology. RESULTS: The spatial distribution of PSMs FI differs between PSMs and according to symptoms and the adjacent degenerative IVD pathology. Furthermore, the region of MF closest to the disc center of rotation appears most susceptible to FI in the presence of symptomatic IVD degeneration. CONCLUSION: Our study identified spatial distribution patterns of FI in the PSMs as a potential diagnostic biomarker that may also provide granular mechanistic insights into spine biomechanics related to cLBP, as well as advancing the use of prior summary measures limited to overall muscle FI.

Using hierarchical unsupervised learning to integrate and reduce multi-level and multi-paraspinal muscle MRI data in relation to low back pain.

PURPOSE: The paraspinal muscles (PSM) are a key feature potentially related to low back pain (LBP), and their structure and composition can be quantified using MRI. Most commonly, quantifying PSM measures across individual muscles and individual spinal levels renders numerous separate metrics that are analyzed in isolation. However, comprehensive multivariate approaches would be more appropriate for analyzing the PSM within an individual. To establish and test these methods, we hypothesized that multivariate summaries of PSM MRI measures would associate with the presence of LBP symptoms (i.e., pain intensity). METHODS: We applied hierarchical multiple factor analysis (hMFA), an unsupervised integrative method, to clinical PSM MRI data from unique cohort datasets including a longitudinal cohort of astronauts with pre- and post-spaceflight data and a cohort of chronic LBP subjects and asymptomatic controls. Three specific use cases were investigated: (1) predicting longitudinal changes in pain using combinations of baseline PSM measures; (2) integrating baseline and post-spaceflight MRI to assess longitudinal change in PSM and how it relates to pain; and (3) integrating PSM quality and adjacent spinal pathology between LBP patients and controls. RESULTS: Overall, we found distinct complex relationships with pain intensity between particular muscles and spinal levels. Subjects with high asymmetry between left and right lean muscle composition and differences between spinal segments PSM quality and structure are more likely to increase in pain reported outcome after prolonged time in microgravity. Moreover, changes in PSM quality and structure between pre and post-spaceflight relate to increase in pain after prolonged microgravity. Finally, we show how unsupervised hMFA recapitulates previous research on the association of CEP damage and LBP diagnostic. CONCLUSION: Our analysis considers the spine as a multi-segmental unit as opposed to a series of discrete and isolated spine segments. Integrative and multivariate approaches can be used to distill large and complex imaging datasets thereby improving the clinical utility of MRI-based biomarkers, and providing metrics for further analytical goals, including phenotyping.

Biomechanical changes in the lumbar spine following spaceflight and factors associated with postspaceflight disc herniation.

BACKGROUND CONTEXT: For chronic low back pain, the causal mechanisms between pathological features from imaging and patient symptoms are unclear. For instance, disc herniations can often be present without symptoms. There remains a need for improved knowledge of the pathophysiological mechanisms that explore spinal tissue damage and clinical manifestations of pain and disability. Spaceflight and astronaut health provides a rare opportunity to study potential low back pain mechanisms longitudinally. Spaceflight disrupts diurnal loading on the spine and several lines of evidence indicate that astronauts are at a heightened risk for low back pain and disc herniation following spaceflight. PURPOSE: To examine the relationship between prolonged exposure to microgravity and the elevated incidence of postflight disc herniation, we conducted a longitudinal study to track the spinal health of twelve NASA astronauts before and after approximately 6 months in space. We hypothesize that the incidence of postflight disc herniation and low back complaints associates with spaceflight-included muscle atrophy and pre-existing spinal pathology. STUDY DESIGN: This is a prospective longitudinal study. PATIENT SAMPLE: Our sample included a cohort of twelve astronaut crewmembers. OUTCOME MEASURES: From 3T MRI, we quantified disc water content (ms), disc degeneration (Pfirrmann grade), vertebral endplate irregularities, facet arthropathy and/ fluid, high intensity zones, disc herniation, multifidus total cross-sectional area (cm2), multifidus lean muscle cross-sectional area (cm2), and muscle quality/composition (%). From quantitative fluoroscopy we quantified, maximum flexion-extension ROM (°), maximum lateral bending ROM (°), and maximum translation (%). Lastly, patient outcomes and clinical notes were used for identifying postflight symptoms associated with disc herniations from 3T MRI. METHODS: Advanced imaging data from 3T MRI were collected at three separate time points in relation to spending six months in space: (1) within a year before launch ("pre-flight"), (2) within a week after return to Earth ("post-flight"), and (3) between 1 and 2 months after return to Earth ("recovery"). Fluoroscopy of segmental kinematics was collected at preflight and postflight timepoints. We assessed the effect of spaceflight and postflight recovery on longitudinal changes in spinal structure and function, as well as differences between crew members who did and did not present a symptomatic disc herniation following spaceflight. RESULTS: Half of our astronauts (n=6) experienced new symptoms associated with a new or previously asymptomatic lumbar disc protrusion or extrusion following spaceflight. We observed decreased multifidus muscle quality following spaceflight in the lower lumbar spine, with a reduced percentage of lean muscle at L4L5 (-6.2%, p=.009) and L5S1 (-7.0%, p=.006) associated with the incidence of new disc herniation. Additionally, we observed reduced lumbar segment flexion-extension ROM for L2L3 (-17.2%, p=.006) and L3L4 (-20.5%, p=.02) following spaceflight, and furthermore that reduced ROM among the upper three lumbar segments (-24.1%, p=.01) associated with the incidence of disc herniation. Existing endplate pathology was most prevalent in the upper lumbar spine and associated with reduced segmental ROM (-20.5%, p=.02). CONCLUSIONS: In conclusion from a 10-year study investigating the effects of spaceflight on the lumbar spine and risk for disc herniation, we found the incidence of lumbar disc herniation following spaceflight associates with compromised multifidus muscle quality and spinal segment kinematics, as well as pre-existing spinal endplate irregularities. These findings suggest differential effects of spinal stiffness and muscle loss in the upper versus lower lumbar spine regions that may specifically provoke risk for symptomatic disc herniation in the lower lumbar spine following spaceflight. Results from this study provide a unique longitudinal assessment of mechanisms and possible risk factors for developing disc herniations and related low back pain. Furthermore, these findings will help inform physiologic countermeasures to maintain spinal health in astronauts during long-duration missions in space.

Measurement of vertebral endplate bone marrow lesion (Modic change) composition with water-fat MRI and relationship to patient-reported outcome measures.

PURPOSE: Vertebral endplate bone marrow lesions ("Modic changes", MC) are associated with chronic low back pain (CLBP). Bone marrow composition in MC is poorly understood. The goals of this study were to: (1) measure bone marrow fat fraction (BMF) in CLBP patients with MC using water-fat MRI and (2) assess the relationship between BMF measurements and patient-reported clinical characteristics. METHODS: In this cross-sectional study, 42 CLBP patients (men, n = 21; age, 48 ± 12.4 years) and 18 asymptomatic controls (men, n = 10; 42.7 ± 12.8 years) underwent 3 T MRI between January 2016 and July 2018. Imaging consisted of T1- and T2-weighted sequences to evaluate MC and spoiled gradient-recalled echo sequence with asymmetric echoes and least-squares fitting to measure BMF. BMF was compared between vertebrae with and without MC using mixed effects models. The relationship between the BMF measurements and patient-reported disability scores was examined using regression. RESULTS: Twenty-seven subjects (26 CLBP, 1 control) had MC, and MC presence coincided with significantly altered BMF. In MC 1, BMF was lower than endplates without MC (absolute difference -22.3%; p < 0.001); in MC 2, BMF was higher (absolute difference 21.0%; p < 0.001). Absolute BMF differences between affected and unaffected marrow were larger in patients with greater disability (p = 0.029-0.032) and were not associated with pain (p = 0.49-0.83). CONCLUSION: BMF is significantly altered in MC. Water-fat MRI enables BMF measurements that may eventually form the basis for quantitative assessments of MC severity and progression.

Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes).

Vertebral endplate bone marrow lesions, visualized on magnetic resonance imaging (MRI) as Modic changes (MC), are associated with chronic low back pain (cLBP). Since guidelines recommend against routine spinal MRI for cLBP in primary care, MC may be underdiagnosed. Serum biomarkers for MC would allow early diagnosis, inform clinical care decisions, and supplement treatment monitoring. We aimed to discover biomarkers in the blood serum that correlate with MC pathophysiological processes. For this single-site cross-sectional study, we recruited 54 subjects with 38 cLBP patients and 16 volunteers without a history of LBP. All subjects completed an Oswestry Disability Index (ODI) questionnaire and 10-cm Visual Analog Score (VAS) for LBP (VASback) and leg pain. Lumbar T1-weighted and fat-saturated T2-weighted MRI were acquired at 3T and used for MC classification in each endplate. Blood serum was collected on the day of MRI. Biomarkers related to disc resorption and bone marrow fibrosis were analyzed with enzyme-linked immune-absorbent assays. The concentration of biomarkers between no MC and any type of MC (AnyMC), MC1, and MC2 were compared. The Area Under the Curve (AUC) of the Receiver Operating Characteristics were calculated for each biomarker and for bivariable biomarker models. We found that biomarkers related to type III and type IV collagen degradation and formation tended to correlate with the presence of MC (p = 0.060-0.088). The bivariable model with the highest AUC was PRO-C3 + C4M and had a moderate diagnostic value for AnyMC in cLBP patients (AUC = 0.73, specificity = 78.9%, sensitivity = 73.7%). In conclusion, serum biomarkers related to the formation and degradation of type III and type IV collagen, which are key molecules in bone marrow fibrosis, correlated with MC presence. Bone marrow fibrosis may be an important pathophysiological process in MC that should be targeted in larger biomarker and treatment studies.

Measuring and reporting of vertebral endplate bone marrow lesions as seen on MRI (Modic changes): recommendations from the ISSLS Degenerative Spinal Phenotypes Group.

PURPOSE: The positive association between low back pain and MRI evidence of vertebral endplate bone marrow lesions, often called Modic changes (MC), offers the exciting prospect of diagnosing a specific phenotype of chronic low back pain (LBP). However, imprecision in the reporting of MC has introduced substantial challenges, as variations in both imaging equipment and scanning parameters can impact conspicuity of MC. This review discusses key methodological factors that impact MC classification and recommends guidelines for more consistent MC reporting that will allow for better integration of research into this LBP phenotype. METHODS: Non-systematic literature review. RESULTS: The high diagnostic specificity of MC classification for a painful level contributes to the significant association observed between MC and LBP, whereas low and variable sensitivity underlies the between- and within-study variability in observed associations. Poor sensitivity may be owing to the presence of other pain generators, to the limited MRI resolution, and to the imperfect reliability of MC classification, which lowers diagnostic sensitivity and thus influences the association between MC and LBP. Importantly, magnetic field strength and pulse sequence parameters also impact detection of MC. Advances in pulse sequences may improve reliability and prove valuable for quantifying lesion severity. CONCLUSIONS: Comparison of MC data between studies can be problematic. Various methodological factors impact detection and classification of MC, and the lack of reporting guidelines hinders interpretation and comparison of findings. Thus, it is critical to adopt imaging and reporting standards that codify acceptable methodological criteria. These slides can be retrieved under Electronic Supplementary Material.

Tidemark Avulsions are a Predominant Form of Endplate Irregularity.

STUDY DESIGN: Descriptive histologic and magnetic resonance imaging study of human cadaveric spines. OBJECTIVE: To identify and characterize common endplate pathologies to form a histologic foundation for an etiology-based classification system. SUMMARY OF BACKGROUND DATA: Irregularities at the spinal disc-vertebra interface are associated with back pain and intervertebral disc herniation injuries. However, there is currently a lack of consensus regarding terminology for classification. This limits the potential for advancing understanding of back pain mechanisms, and prohibits meaningful comparisons for identifying priorities for prevention and treatment. Prior classification systems largely rely on observations from clinical imaging, which may miss subtle pathologic features. METHODS: Fifteen cadaveric spines with moderate to severe disc degeneration were obtained and scanned with MRI in the sagittal plane using two-dimensional T1-weighted and T2-weighted fast spin-echo sequences. Eighty-nine lumbar and lower thoracic bone-disc-bone motion segments were extracted, fixed, sectioned, and stained for histologic evaluation. Focal endplate irregularities were identified and categorized based on features that inferred causation. The presence, type, and anatomic location were recorded. A classification system with three major categories of focal endplate irregularities was created. RESULTS: Disc-vertebra avulsion and vertebral rim degeneration were more common than subchondral nodes: 50% of irregularities were classified as rim degeneration (75/150), 35% were classified as avulsions (52/150), and 15% were classified as nodes (23/150). Ninety percent of avulsions were subclassified as "tidemark avulsions," a highly prevalent form of endplate irregularity in which the outer annulus separates from the vertebra at the tidemark. These tidemark avulsions have not been previously described, yet are visible on T2-weighted MRI as high-intensity regions. CONCLUSION: This study provides histologic basis for a system to classify focal endplate irregularities. Included is a previously unidentified but prevalent finding of tidemark avulsions, which are visible with both histology and magnetic resonance imaging. These observations will help clinicians better organize patients into meaningful groups to facilitate diagnosis, treatment, and clinical research. LEVEL OF EVIDENCE: 3.

From the international space station to the clinic: how prolonged unloading may disrupt lumbar spine stability.

BACKGROUND CONTEXT: Prolonged microgravity exposure is associated with localized low back pain and an elevated risk of post-flight disc herniation. Although the mechanisms by which microgravity impairs the spine are unclear, they should be foundational for developing in-flight countermeasures for maintaining astronaut spine health. Because human spine anatomy has adapted to upright posture on Earth, observations of how spaceflight affects the spine should also provide new and potentially important information on spine biomechanics that benefit the general population. PURPOSE: This study compares quantitative measures of lumbar spine anatomy, health, and biomechanics in astronauts before and after 6 months of microgravity exposure on board the International Space Station (ISS). STUDY DESIGN: This is a prospective longitudinal study. SAMPLE: Six astronaut crewmember volunteers from the National Aeronautics and Space Administration (NASA) with 6-month missions aboard the ISS comprised our study sample. OUTCOME MEASURES: For multifidus and erector spinae at L3-L4, measures include cross-sectional area (CSA), functional cross-sectional area (FCSA), and FCSA/CSA. Other measures include supine lumbar lordosis (L1-S1), active (standing) and passive (lying) flexion-extension range of motion (FE ROM) for each lumbar disc segment, disc water content from T2-weighted intensity, Pfirrmann grade, vertebral end plate pathology, and subject-reported incidence of chronic low back pain or disc injuries at 1-year follow-up. METHODS: 3T magnetic resonance imaging and dynamic fluoroscopy of the lumbar spine were collected for each subject at two time points: approximately 30 days before launch (pre-flight) and 1 day following 6 months spaceflight on the ISS (post-flight). Outcome measures were compared between time points using paired t tests and regression analyses. RESULTS: Supine lumbar lordosis decreased (flattened) by an average of 11% (p=.019). Active FE ROM decreased for the middle three lumbar discs (L2-L3: -22.1%, p=.049; L3-L4: -17.3%, p=.016; L4-L5: -30.3%, p=.004). By contrast, no significant passive FE ROM changes in these discs were observed (p>.05). Disc water content did not differ systematically from pre- to post-flight. Multifidus and erector spinae changed variably between subjects, with five of six subjects experiencing an average decrease 20% for FCSA and 8%-9% for CSA in both muscles. For all subjects, changes in multifidus FCSA strongly correlated with changes in lordosis (r2=0.86, p=.008) and active FE ROM at L4-L5 (r2=0.94, p=.007). Additionally, changes in multifidus FCSA/CSA correlated with changes in lordosis (r2=0.69, p=.03). Although multifidus-associated changes in lordosis and ROM were present among all subjects, only those with severe, pre-flight end plate irregularities (two of six subjects) had post-flight lumbar symptoms (including chronic low back pain or disc herniation). CONCLUSIONS: We observed that multifidus atrophy, rather than intervertebral disc swelling, associated strongly with lumbar flattening and increased stiffness. Because these changes have been previously linked with detrimental spine biomechanics and pain in terrestrial populations, when combined with evidence of pre-flight vertebral end plate insufficiency, they may elevate injury risk for astronauts upon return to gravity loading. Our results also have implications for deconditioned spines on Earth. We anticipate that our results will inform new astronaut countermeasures that target the multifidus muscles, and research on the role of muscular stability in relation to chronic low back pain and disc injury.

Glucosamine HCl alters production of inflammatory mediators by rat intervertebral disc cells in vitro.

BACKGROUND CONTEXT: Studies on cartilage have shown anti-inflammatory effects of glucosamine related to inhibition of inflammatory mediators. Intradiscal injection of glucosamine has been proposed as a treatment for chronic discogenic low back pain. However, there have been no studies of the direct effects of glucosamine on disc cells. PURPOSE: To determine the effects of glucosamine HCl on pro-inflammatory mediator production by intervertebral disc cells. STUDY DESIGN: An in vitro, experimental study of interleukin-1 (IL-1) stimulated rat intervertebral disc cells treated with and without glucosamine HCl. METHODS: Rat annulus and nucleus cells were cultured in alginate beads and exposed to IL-1a (10 ng/mL)+glucosamine HCl (4.5 mg/mL), IL-1 alone, or neither for 4 and 7 days. Cell viability and IL-6, tumor necrosis factor alpha (TNF-alpha), prostaglandin E(2) (PGE(2)), and NO levels in the medium were quantified and compared across treatments. RESULTS: Annulus cells, 7 days: Glucosamine completely inhibited IL-6 and TNF-alpha, increased NO (by 75%), and reduced viability (by 89%) compared with IL-1 alone. Nucleus cells, 7 days: Glucosamine reduced IL-6 (by 89%), PGE(2) (91%), and NO (90%) with no effect to viability. CONCLUSIONS: Glucosamine inhibits inflammatory mediator production by IL-1 stimulated disc cells, but also adversely affects the viability of rat annulus cells. The response is cell-type dependent, illustrated by differences for annulus and nucleus cells.

The short-term effects of electrosurgical ablation on proinflammatory mediator production by intervertebral disc cells in tissue culture.

BACKGROUND CONTEXT: Percutaneous discectomy can be performed by a variety of methods. One method, electrosurgical ablation, has been shown in a chronic animal model to alter the expression of inflammatory cytokines in degenerated discs. PURPOSE: To determine whether electrosurgical ablation has an acute direct effect on proinflammatory mediator production by disc cells. STUDY DESIGN: A short-term in vitro study using normal and interleukin (IL)-1alpha stimulated porcine disc cells cultured in alginate gel to evaluate the biochemical effects of electrosurgical ablation. METHODS: Porcine annulus and nucleus cells were embedded into alginate gels and cultured using control culture media or IL-1alpha-treated media for 6 days before ablation treatment. Treated gels were ablated by using a radiofrequency-based electrosurgical device for 5 seconds and cultured an additional 3 or 6 days. IL-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2), nitric oxide (NO), and heat shock protein-70 (Hsp70) levels in culture medium were measured. Levels were normalized to DNA and compared between ablated and shams. RESULTS: For normal annulus cells, there were no significant changes in cytokine levels between ablation and sham groups. For normal nucleus cells, ablation produced significantly greater levels of IL-8 at 3 days and 6 days, Hsp70 at 3 days but not 6 days, and NO at 6 days. PGE2 was also increased at 3 days and 6 days but not significantly. For IL-1-stimulated annulus cells, IL-6 and NO in the ablation group were decreased at 3 days relative to the control group. However, IL-6, IL-8, PGE2, and Hsp70 were significantly increased in the 6-day ablation group. For degenerated nucleus cells, IL-6, IL-8, and TNF-alpha were significantly decreased in the ablation group at both 3 days and 6 days. Ablation resulted in reduced PGE2 at 3 days but not 6 and reduced Hsp70 and NO at 6 days. CONCLUSIONS: The results show that electrosurgical ablation has an acute direct effect on proinflammatory mediator production by disc cells. The effect produced depends on disc cell phenotype, the mediator, and time. These direct biologic effects may be a mechanism of pain relief after percutaneous discectomy using electrosurgical ablation. However, the measured responses are limited to the short-term (1 week), and the existence of a prolonged effect remains to be determined.

Measurement of in vivo lumbar intervertebral disc pressure during spinal manipulation: a feasibility study.

This paper presents the first reported measurements of lumbar intervertebral disc pressure in vivo during spinal manipulation. A pressure transducer was inserted into the nucleus pulposus of one normal-appearing lumbar disc in an asymptomatic adult volunteer. Pressures were recorded during several body positions and maneuvers, then during spinal manipulation, and lastly during a repetition of the preintervention body positions. Baseline pressures in the prone and side-lying positions measured 110 kPa and 150 kPa, respectively. During the manipulation, pressure rose to a peak of 890 kPa over 250 ms. Immediately following, pressures in the prone and side-lying positions measured 150 kPa and 165 kPa, respectively. These data do not support the hypotheses that manipulation can reduce a herniation by decreasing intradiscal pressure, or cause a herniation by raising pressure to failure levels. Further work may lead to a better understanding of this treatment method.

Percutaneous plasma decompression alters cytokine expression in injured porcine intervertebral discs.

BACKGROUND CONTEXT: Discectomy is a surgical technique commonly used to treat bulging or herniated discs causing nerve root compression. Clinical data suggest discectomy may also help patients with contained discs and no clear neural compromise. However, the mechanisms of clinical efficacy are uncertain, and consequently bases for treatment optimization are limited. PURPOSE: To determine the effect of percutaneous plasma decompression on the histologic, morphologic, biochemical and biomechanical features of degenerating intervertebral discs. STUDY DESIGN: An adult porcine model of disc degeneration was used to establish a degenerative baseline against which to evaluate discectomy efficacy. OUTCOME MEASURES: Cytokines interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha were measured from tissue samples using enzyme-linked immunosorbent assay. Histology and morphology images were rated for degenerative findings (of cells and matrix) in both the nucleus and annulus. Proteoglycan content was determined, and intact specimen stiffness and flexibility were measured biomechanically. Magnetic resonance images were collected for biomechanical specimens. METHODS: Using a retroperitoneal surgical approach, stab incisions were made in four or five lumbar discs per spine in 12 minipigs. Animals were allocated into one of three groups: 6-week recovery, 12-week recovery and percutaneous plasma decompression using an electrosurgical device at 6 weeks with recovery for 6 additional weeks. Four additional animals served as controls. RESULTS: Discs treated with discectomy had a significant increase in IL-8 and a decrease in IL-1 as compared with the 12-week, nontreated discs. There were no significant differences in morphologic and biomechanical parameters or proteoglycan content between treated discs and time-matched, nontreated discs. CONCLUSIONS: Our results demonstrate that percutaneous plasma discectomy alters the expression of inflammatory cytokines in degenerated discs, leading to a decrease in IL-1 and an increase in IL-8. Whereas both IL-1 and IL-8 have hyperalgesic properties, IL-1 is likely to be a more important pathophysiologic factor in painful disc disorders than IL-8. Therefore, the alteration in cytokine expression that we observed is consistent with this effect as a mechanism of pain relief after discectomy. In addition, given that IL-1 is catabolic in injured tissue and IL-8 is anabolic, our results suggest that a percutaneous plasma discectomy may be capable of initiating a repair response in the disc.

Biochemical injection treatment for discogenic low back pain: a pilot study.

BACKGROUND CONTEXT: Biochemical treatment options including attempts at intervertebral disc restoration are desirable for the physiologic treatment of degenerative disc disease. PURPOSE: This was a pilot study to test the potential effectiveness of intradiscal injection therapy using agents known to induce proteoglycan synthesis in the treatment of intervertebral disc disease. STUDY DESIGN: Prospective, within subject, experimental design was applied in the study. PATIENT SAMPLE: Thirty patients, average age 46.5 years, with chronic intractable low back pain of 8.5 years average duration, took part in the study. All patients had lumbar discography with reproduction of pain. OUTCOME MEASURES: Pretreatment Roland-Morris disability scores and visual analogue scores were compared with 1-year follow-up posttest values of these scores. METHODS: Lumbar intervertebral discs were injected with a solution of glucosamine and chondroitin sulfate combined with hypertonic dextrose and dimethlysulfoxide (DMSO). Assessment of pain and disability was completed before treatment and an average of 12 months after the last treatment. RESULTS: Posttreatment Roland-Morris scores for the entire group of 30 patients of 6.4+/-.994 were significantly (p<.001) lower than pretreatment scores of 12.0+/-.92 (mean+/-SE). The posttreatment visual analogue scores of 3.00+/-.44 were also significantly less than the pretreatment of 6.11+/-.33 (mean+/-SE). Although the results were statistically significant for the 30 patients as a whole, 17 of the 30 patients (57%) improved markedly with an average of 72% improvement in disability scores and 76% in visual analogue scores. The other 13 patients (43%) had little or no improvement. Patients who did poorly included those with failed spinal surgery, spinal stenosis and long-term disability. There were no complications or serious side effects, although postinjection pain was moderate to severe for 48 to 72 hours and required epidural steroids in five cases. CONCLUSIONS: The results of this pilot study suggest that intradiscal injection therapy with glucosamine, chondroitin sulfate, hypertonic dextrose and DMSO warrants further evaluation with randomized controlled trials.

Disc stimulation and patterns of referred pain.

STUDY DESIGN: Prospective, within-subjects, observational experimental design. OBJECTIVES: To determine the pattern of pain response to noxious stimulation of the intervertebral disc. SUMMARY OF BACKGROUND DATA: Experimental studies have demonstrated that noxious stimulation of interspinous ligaments, facet joints, and paravertebral muscles causes referred pain into the extremity, with the distal extent of radiation dependent on the intensity of stimulation. Analogous studies have not been performed on the lumbar intervertebral disc. METHODS: A total of 25 consecutive patients meeting inclusion criteria completed a pain diagram before undergoing the intradiscal electrothermal annuloplasty procedure. The location, intensity, and familiarity of any pain provoked during disc heating were correlated with presenting symptoms and duration of heating. RESULTS: During disc heating, 68% of patients reported exact reproduction of their presenting pain, in both pain quality and location. None of the patients experienced unfamiliar pain during the procedure. The pattern of pain reproduction was consistent; pain originated proximally and progressed distally as stimulus intensity increased. CONCLUSION: Noxious stimulation of the intervertebral disc may result in low back and referred extremity in patients presenting with these symptoms. The distal extent of pain produced depends on the intensity of stimulation. Disc stimulation may reproduce pain that extends to below the knee.