Joel Saal

High levels of inflammatory phospholipase A2 activity in lumbar disc herniations.

Inflammation of neural elements is frequently mentioned clinically in association with lumbar radiculopathy. Mechanical embarrassment of neural elements by definable structural abnormalities is inadequate as a sole explanation of nerve injury in this condition. The purpose of this study was to demonstrate whether an enzymatic marker for inflammation (phospholipase A2) could be identified in human disc samples removed at surgery for radiculopathy due to lumbar disc disease. Samples were assayed for phospholipase A2 activity. The level of activity in the disc samples was compared with values obtained from other human tissues using the same assay. Specific activity (percent hydrolysis radiolabelled substrate) ranged from 238 to 1,014.5 nmol/min/mg. Mean activity for the human disc material was 568.7 nmol/min/mg, compared with 0.006 nmol/min/mg for human PMN, and 12.1 nmol/min/mg for inflammatory human synovial effusion. The pH and cation-related activity were identical to those demonstrated for phospholipase A2 inflammatory conditions. Human lumbar disc phospholipase A2 activity is from 20- to 100,000-fold more active than any other phospholipase A2 that has been described. As the enzyme responsible for the liberation of arachidonic acid from cell membranes, phospholipase A2 is the rate-limiting step in the production of prostaglandins and leukotrienes. These data establish biochemical evidence of inflammation at the site of lumbar disc herniations.

Nonoperative treatment of herniated lumbar intervertebral disc with radiculopathy: an outcome study

The functional outcome of patients with lumbar herniated nucleus pulposus without significant stenosis was analyzed in a retrospective cohort study. Inclusion criteria were as follows: 1) a chief complaint of leg pain, primarily; 2) a positive straight leg raising (SLR) at less than 60° reproducing the leg pain; 3) a computed tomography (CT) scan demonstrating a hemiated nucleus pulposus without significant stenosis by a radiologists reading, which was also confirmed by the authors; 4) a positive electromyogram (EMG) demonstrating evidence of radiculopathy; and 5) response to a follow-up questionnaire. All patients had undergone an aggressive physical rehabilitation program consisting of back school and stabilization exercise training. Of a total of 347 consecutively identified patients, 64 patients with an average follow-up time of 31.1 months met the inclusion criteria and constituted the study population. They were sent questionnaires that inquired about activity level, pain level, work status, and further medical care. The patients with neurologic loss, extruded discs, and those seeking a second opinion regarding surgery were identified and subgrouped. Results for the total group included 90% good or excellent outcome with a 92% return to work rate. For the subgroups with extruded discs and second opinions, 87% and 83% had good or excellent outcomes, respectively, all (100%) of whom returned to work. Sick leave time for these subgroups was 2.9 months (±1.4 months) and 3.4 months (±1.7 months), respectively. These results compared favorably with previously published surgical studies. Four of six patients who required surgery were found to have stenosis at operation. There was no statistically significant difference in outcome in the patients with neurologic weakness or with extruded discs from the total study population. This study demonstrates that herniated nucleus pulposus of a lumbar intervertebral disc with radiculopathy can be treated very successfully with aggressive nonoperative care. Surgery should be reserved for those patients for whom function cannot be satisfactorily improved by a physical rehabilitation program. Failure to respond to nonoperative care should suggest the presence of stenosis.

The natural history of lumbar intervertebral disc extrusions treated nonoperatively

The purpose of this study was to evaluate the natural history of morphologic changes within the lumbar spine in patients who sustained lumbar disc extrusions. All patients in this study were treated nonoperatively for radicular pain and neurologic loss. The following questions were addressed: 1) Does perithecal or perineural fibrosis result when extrusions are not removed surgically, and 2) Do disc extrusions spontaneously resolve, and, if so, how rapidly? The study population consisted of 11 patients with extrusions and radiculopathy. All patients were successfully treated nonoperatively. All had a primary complaint of leg pain and all had positive straight leg raising reproducing their leg pain at less than or equal to 60°. Additionally, 87% had muscle weakness on a neurologic basis in a root level distribution corresponding to the site of disc pathology. Computed tomographic (CT) examinations were obtained on all patients at the inception of treatment. These studies were compared with follow-up MRI studies. The initial CT scans were evaluated for the following criteria: disc size and position, thecal sac effacement, nerve root enlargement or displacement, and evidence of central or intervertebral canal stenosis. In addition to the pathomorphology evaluated on the CT scans, follow-up MRI studies also evaluated disc hydration at the herniated and contiguous levels, and the presence of perithecal or perineural fibrosis. The following grading system was used to evaluate change in fragment size on the follow-up studies: Grade 1—0 to 50% decrease in size; Grade 2—50 to 75% decrease in size; Grade 3—75 to 100% decrease in size. Results on follow-up MRI examinations were as follows: 11% of the patients had Grade 1—2 residual fragments; 36% had Grade 2—4 fragments; and 46% had Grade 3—5 fragments. Associated morphologic changes were as follows: no patients had perithecal or perineural fibrosis, 1 patient had a progression of stenosis, and all patients had disc desiccation at the level of disc herniation with contiguous levels being normally hydrated. All patients had a decrease in neural impingement. The interval between the initial presentation and follow-up was a median of 25 months with a range of 8 to 77 months.

Intradiscal Electrothermal Treatment for Chronic Discogenic Low Back Pain : A Prospective Outcome Study With Minimum 1-Year Follow-Up

Study Design. Prospective longitudinal study with a minimum 2-year follow-up. Objective. To assess the long-term outcome of a group of patients with chronic discogenic low back pain who had failed to improve with comprehensive nonoperative care and who were subsequently treated with intradiscal electrothermal therapy (IDET). Summary of Background Data. Previous reports of patient outcomes at 1 year after IDET have demonstrated statistically significant improvement. Methods. The study group comprised 58 patients with chronic symptoms of more than 6 months who failed to improve with nonoperative care and subsequently underwent IDET. VAS pain scores, SF-36 scores, and sitting tolerance times were collected pretreatment and at 6, 12, and 24 months. Results. Mean duration of pre-IDET symptoms was 60.7 months. The minimum follow-up at data collection was 24 months. The study group (n = 58) demonstrated a significant improvement in pain as demonstrated by statistically significant improvement in VAS scores and bodily pain SF-36 scores. The IDET-treated group demonstrated a significant improvement in physical function as noted by statistically significant improvement in sitting tolerance times and physical function SF-36 scores. Bodily pain and physical function scores demonstrated significant improvement between the 1- and 2-year observation points. Additionally, quality of life improvement was demonstrated by a statistically significant improvement in all the SF-36 subscales. Conclusions. A cohort of patients with chronic discogenic low back pain who had failed to improve with comprehensive nonoperative care demonstrated a statistically significant improvement in pain, physical function, and quality of life at 2 years after IDET.

The role of inflammation in lumbar pain

The clinical features of many cases of low back pain is inadequately explained by anatomic abnormalities alone. A pathophysiologic mechanism that includes a combination of mechanical and biochemical factors is an alternative explanation that is accompanled by less paredox than a purely structural paradigm. A potential unifying feature includes inflammation of neural elements caused by the chemical components of the intervertebral disc. There is a historical basis to the concept of an immunologic potential of the lumbar disc. No discrete insitu evidence or discrete mechanism has been previously identified. The recent demonstration of immunohistopathologic evidence of an immunocompetent celluiar response at the epidural interface of lumbar HNPs supports the concept of the immunogenic capacity of nucleus pulposus. The identification of high levels of an inflammatory enzyme, phospholipase A2, in lumbar herniated and degenerative discs presents the basis for a direct inflammogenic capability of lumbar discs, separate from a immunologic mechanism. Subsequent experimental findings of conduction block and perineural inflammation as a consequence of extrathecal application of autologous nucleus pulposus and axonal injury after animal nerve injection of the human disc phospholipase A2 further validates this concept. There is a strong theroretic basis to support the concept that the clinical features of many lumbar disc patients may be explained by inflammation caused by biochemical factors alone or combined with mechanical deformation of lumbar tissues, rather than mechanical factors alone.

Management of Chronic Discogenic Low Back Pain With a Thermal Intradiscal Catheter : A Preliminary Report

Study Design. A prospective nonrandomized clinical trial. Objective. To determine the outcome in a group of patients with chronic, function-limiting low back pain who met the criteria for interbody fusion surgery, but were instead treated with an intradiscal thermal catheter (SpineCath, Oratec Interventions, Inc., Menlo Park, CA). Summary of Background Data. This study represents the first reported trial of treatment for chronic discogenic low back pain with a novel thermal intradiscal catheter. Methods. The authors evaluated 25 consecutive patients. The minimum duration of nonoperative care with the authors was 6 months. The visual analog pain scores, sitting tolerance times, and SF-36 summary scores were tabulated. Results. The mean follow-up period was 7 months, and the mean duration of symptoms 58.5 months. Of the 25 patients, 20 (80%) reported a reduction of at least 2 points in visual analog pain scores, and 18 (72%) reported an improvement in sitting tolerance as well as reduction or discontinuance of analgesic medication. Visual analog pain scores improved by a mean reduction of 3.74, a 51% change (P = 0.0001). On the SF-36 physical function subscale, 72% of the patients improved by a mean increase of 15 points (P = 0.001), a mean change of 38%, and by a mean increase of 14 points on the bodily pain subscale (P = 0.004), a mean change of 48%. Conclusions. A statistically significant improvement in functional outcome was obtained in patients with chronic discogenic low back pain treated thermally by the SpineCath.

Human disc phospholipase A2 is inflammatory

Human discs have been demonstrated to contain high levels of phospholipase A2. As the enzyme responsible for the liberation of arachidonic acid from membranes, this enzyme has a theoretical inflammatory potential. Hernlated lumbar discs have a higher level of phospholipase A2 than do normal discs. The purpose of this study was to evaluate the inflammatory capability of purified human disc phospholipase A2. Phospholipase A2 extracted and purified from human disc was found to be inflammatory. Its inflammatory capability was directly related to its ability to function enzymatically. When the enzyme was treated with parabromophenacyl bromide (p-BPB) to specifically alkylate the active site histidine and block catalytic activity, the ability of the modified protein to produce edema was markedly reduced. Careful regulation of the activity of this enzyme is important in vivo because its inflammatory potential could result in disc degeneration and nerve injury.

General principles of diagnostic testing as related to painful lumbar spine disorders

Study Design. The literature on diagnostic tests available to the spine clinician for the evaluation of chronic low back pain was reviewed. Objectives. To review critically the available information and data on invasive diagnostic tests used for evaluation of chronic low back pain. Summary of Background Information. Numerous published studies have described the technique and clinical results of diagnostic blocks for chronic low back pain. There are various methodologies, but most lack of an adequate “gold standard” with which to compare the results of the diagnostic test. Methods. The available published studies of diagnostic tests commonly used in the evaluation of chronic low back pain were reviewed, with a focus on invasive techniques. The techniques were evaluated on the basis of the data available to support the conclusions that could be drawn for each of these techniques. The principles of diagnostic testing, including specificity and sensitivity, were reviewed and applied in the context of the data available for each of these invasive tests. Results. The essential features the clinician seeks in a diagnostic test are accuracy, safety, and reproducibility. It is essential to have a gold standard with which to compare the accuracy of a given diagnostic test. There is no completely reliable gold standard with which to compare a diagnostic test (or injection) when the absence of pain is the end point. The clinical setting in which the test is used directly affects the test results. The prevalence of the disease therefore affects the meaningfulness of the test results. Imaging studies have their greatest value in the exclusion of other conditions. These studies alone were not adequate for predicting the patients who would respond to controlled diagnostic blocks of the facet joint. Facet joint diagnostic blockade probably is most accurately performed by median nerve branch block. The greatest specificity for a positive response to a facet denervation procedure is achieved when the diagnosis is established via highly controlled anesthetic blocks. Over the past few decades, the sacroiliac joint has received varying degrees of interest as an important pain generator of low back pain. Despite testimonials to the contrary, no diagnostic physical examination has correlated with sufficient specificity to diagnose this condition reliably from a clinical standpoint. Lumbar discography has been one of the single most controversial subjects in the management of degenerative, painful lumbar spine conditions. The specificity and sensitivity are high for the diagnosis of disc degeneration. The question that revolves around discography concerns the accuracy of this test for the diagnosis of discogenic pain. An integral part of the problem is the lack of an adequate gold standard. In a comparison of nerve root blockade, sciatic nerve block, posterior ramus block, and subcutaneous injection in a cohort of patients with sciatica, the sensitivity of nerve root block was very high, with only a moderate level of specificity. In the case of diagnostic selective nerve blocks used for evaluation of complex or protean nerve compression, surgical confirmation and clinical results should be a reliable gold standard. Conflicting results have been presented depending on the target lesion and method of study. Conclusions. There are inherent limitations in the accuracy of all diagnostic tests. The tests used to diagnose the source of a patient’s chronic low back pain require accurate determination of the abolition or reproduction of the patient’s painful symptoms.

Application of spinal ablative techniques for the treatment of benign chronic painful conditions: history, methods, and outcomes.

Study Design. The literature on current neuroablative techniques for treating benign chronic painful conditions is comprehensively reviewed. Objective. To provide the reader with an understanding of the indications, techniques, and outcomes for the various ablative procedures used to treat chronic pain syndromes. Summary of Background Data. Neuromodulatory techniques are rapidly supplanting the traditional neuroablative procedures used to treat many types of pain. Methods. A MEDLINE search was conducted for each of the following procedures: radiofrequency facet denervation, cordotomy, myelotomy, sympathectomy, DREZotomy, rhizotomy, and ganglionectomy. In the review of each article, special attention given to the outcome, length of follow-up, complications, and number of patients. Summaries of this data were compiled to provided historical perspective, current techniques, indications, and outcomes for each of the aforementioned procedures. The outcomes cited for each procedure generally represent the data from the three or four largest series with adequate follow-up length. Results. The aforementioned procedures have 30% to 90% success rates, with success defined as at least a 50% reduction in perceived pain. These results tend to diminish with time. However, most are associated with a significant degree of morbidity and relatively high complication rates. In addition, many of the techniques lead to deafferentation pain syndromes. Conclusions. Ablative spinal techniques offer pain relief for many patients, but the use of these methods should be considered carefully in the light of available nondestructive procedures that may achieve similar goals with potentially lower morbidities.

Chronic pain of spinal origin

The cost of chronic benign spinal pain is large and growing. The costs of interventional treatment for spinal pain were at a minimum of