The Peridural Membrane of the Human Spine is Well Innervated.

There is evidence that low back pain may originate from a peridural membrane (PDM) at the inferior and medial aspect of neural foramen of the lumbar spine. The objective of this investigation was to determine if this membrane contains neural elements suggestive of sensory innervation with nociceptive function. Spines of four embalmed and three non-embalmed human cadavers were dissected using a sagittal approach to the neural foramen. Seventeen samples of the peridural membrane overlying the neural foramen were collected for immunohistochemistry (IHC) examination by light microscopy and transmission electron microscopy (TEM). Chromagin tagged antibodies to protein gene product 9.5 (PGP9.5) and S-100, and fluorescent antibodies to substance P and calcitonin gene related peptide (CGRP) were used to label neural structures in tissue sections cut from paraffin embedded blocks. This approach allows good visualization of all neural elements, small sensory, and nociceptive nerve fibers in particular. Neural elements were found in all samples. Marked presence of small nerve fibers was observed in 12 of 15 samples. IHC and TEM evaluation revealed myelinated as well as unmyelinated fibers in the peridural membrane. CGRP and substance P immunoreactive fibers indicative of nociceptive function were abundant. These findings confirm and expand evidence that the peridural membrane in human is well innervated and contains sensory nociceptive nerve fibers suggestive of a nociceptive function of the membrane.

Treatment of Common Low Back Pain: A New Approach to an Old Problem.

Low back pain is very common, but the pathophysiology is poorly understood. We present a new hypothesis regarding the pathophysiology of common low back pain supported by our flexible endoscopic observations of the epidural cavity (epiduroscopy), anatomic dissection of embalmed and fresh cadavers, and careful review of preexisting information available on the anatomy of the epidural space and neuroforamen. A new approach to the treatment of common low back pain based on the hypothesis was developed and is presented in the case reports of five patients. Treatment focuses on a perichondrium derivative; the peridural membrane, which creates a suprapedicular compartment in the neuroforamen where we hypothesize inflammatory material accumulates. This produces common low back pain by causing inflammation and sensitization of the peridural membrane and periosteum that forms the boundaries of this compartment. Percutaneous Ablation and Curettage and Inferior Foraminotomy (PACIF(sm)) aims to destroy the peridural membrane, denervate sensitive structures, and remove inflammatory tissues from the suprapedicular canal. The proposed mechanism of action and safety of PACIF(sm) is discussed in the context of epidural and neuroforaminal anatomy. As shown by the five case reports, PACIF(sm) appears to be highly effective and safe, warranting further evaluation.

Assessment of methodologic quality of randomized trials of interventional techniques: development of an interventional pain management specific instrument.

BACKGROUND: A major component of a systematic review is an assessment of the methodological quality and bias of randomized trials. The most commonly utilized methodological quality assessment and bias assessment for randomized trials is by the Cochrane Review Group. While this is not a "gold standard," it is an indication of the current state-of-the-art review methodology. There is, however, no specific instrument to assess the methodological quality of manuscripts published for interventional techniques. OBJECTIVES: Our objective was to develop an instrument specifically for interventional pain management, to assess the methodological quality of randomized trials of interventional techniques. METHODS: Item generation for the instrument was based on a definition of quality, to the extent to which the design and conduct of the trial were congruent with the objectives of the trial. Applicability was defined as the extent to which the trial produced procedures could be applied with contemporary interventional pain management techniques. Multiple items based on Cochrane review criteria were utilized along with specific requirements for interventional techniques. RESULTS: A total of 22 items were developed which formed IPM-QRB or Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment tool. This included 9 of the 12 items from the Cochrane review criteria with definition of some items that were repetitive or duplicate, and the addition of 13 new items. The results were compared for inter-rater reliability of Cochrane review criteria and IPM-QRB, and inter-instrument reliability. The assessment was performed in multiple stages with an initial learning curve. The final assessment was for 4 randomized controlled trials (RCTs) utilizing both Cochrane review criteria and IPM-QRB criteria. The inter-rater agreement for Cochrane review criteria with overall intra-class correlation coefficient was 0.407 compared to an intra-class correlation coefficient of 0.833 for IPM-QRB criteria. The inter-rater agreement was superior for IPM-QRB criteria compared to Cochrane review criteria despite twice the items of Cochrane review criteria as IPM-QRB criteria with the detailed nature of assessment. LIMITATIONS: Limited validity or accuracy assessment of the instrument and the large number of items to be scored. CONCLUSION: We have developed a new comprehensive instrument to assess the methodological quality of randomized trials of interventional techniques. This instrument is superior to Cochrane review methodology criteria in that it provides more extensive and specific information for interventional techniques that will be useful in assessing the methodologic quality and bias of interventional techniques.

Development of an interventional pain management specific instrument for methodologic quality assessment of nonrandomized studies of interventional techniques.

BACKGROUND: The major component of a systematic review is assessment of the methodologic quality and bias of randomized and nonrandomized trials. While there are multiple instruments available to assess the methodologic quality and bias for randomized controlled trials (RCTs), there is a lack of extensively utilized instruments for observational studies, specifically for interventional pain management (IPM) techniques. Even Cochrane review criteria for randomized trials is considered not to be a "gold standard," but merely an indication of the current state of the art review methodology. Recently a specific instrument to assess the methodologic quality of randomized trials has been developed for interventional techniques. OBJECTIVES: Our objective was to develop an IPM specific instrument to assess the methodological quality of nonrandomized trials or observational studies of interventional techniques. METHODS: The item generation for the instrument was based on a definition of quality, to the extent to which the design and conduct of the trial were congruent with the objectives of the study. Applicability was defined as the extent to which procedures produced by the study could be applied using contemporary IPM techniques. Multiple items based on Cochrane review criteria and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) were utilized. RESULTS: A total of 16 items were developed which formed the IPM-QRBNR tool. The assessment was performed in multiple stages. The final assessment was 4 nonrandomized studies. The inter-rater agreement was moderate to good for IPM-QRBNR criteria. LIMITATIONS: Limited validity or accuracy assessment of the instrument and the large number of items to be scored were limitations. CONCLUSION: We have developed a new comprehensive instrument to assess the methodological quality of nonrandomized studies of interventional techniques. This instrument provides extensive information specific to interventional techniques is useful in assessing the methodological quality and bias of observational studies of interventional techniques.

Lumbosacral epiduroscopy findings predict treatment outcome.

OBJECTIVE: The aim of this study was to evaluate the significance of diagnostic markers obtained through epiduroscopy by evaluating the accuracy of outcome prediction after treatment of epidural pathology using epiduroscopy. DESIGN: A prospective observational study of 139 patients was performed. Patients with chronic low back and leg pain were included. Of the 150 patients who underwent epiduroscopy in the year 2008 at a US hospital, 139 were available for evaluation at 1 month. STUDY: Outcome of treatment was predicted based on direct visual information (hyperemia, vascularity, and fibrosis) and mechanical information (pain to touch, contrast spread, and patency) obtained through epiduroscopy. MAIN OUTCOME MEASURES: Outcome of treatment was measured at 1 month. Accuracy of prediction of outcome was calculated using contingency tables and odds ratios. RESULTS: A prediction of outcome was made in 114 of 139 patients (82%). This prediction was correct in 89 of these 114 patients (accuracy of 78%). The sensitivity and specificity of epiduroscopy with respect to the prediction of outcome were 75% and 82%, respectively. These results were statistically significant (P < 0.01). In 25 of the 139 patients (18%), discrete epidural pathology was not observed. Nine of these 25 patients reported good relief after epiduroscopy. The sensitivity and specificity of epiduroscopy in the diagnosis of epidural pathology were 91% and 39%, respectively. These results were not statistically different (P > 0.1). CONCLUSION: Our results show that lumbosacral epiduroscopy predicts outcome of treatment accurately in the majority of patients. This suggests that information obtained through epiduroscopy may carry significant diagnostic and prognostic value.

Epiduroscopy for patients with lumbosacral radicular pain.

Lumbosacral radicular pain is a pain in the distribution area of one of the nerves of the lumbosacral plexus, with or without sensory and/or motor impairment. A major source of lumbosacral radicular pain is failed back surgery, which is defined as persistent or recurrent pain, mainly in the region of the lower back and legs even after technically, anatomically successful spine surgeries. If lumbosacral radicular neuropathic pain fails to respond to conservative or interventional treatments, epiduroscopy can be performed as part of a multidisciplinary approach. Epiduroscopy aids in identifying painful structures in the epidural space, establishing a diagnosis and administering therapy. The novelty consists in the use of an epiduroscope to deliver therapies such as adhesiolysis and targeted administration of epidural medications. Clinical trials report favorable treatment outcomes in 30% to 50% of patients. Complications are rare and related to the rate or volume of epidural fluid infusion or inadvertent dural puncture. In patients with lumbosacral radicular pain, especially after back surgery, epiduroscopy with adhesiolysis may be considered (evidence rating 2 B+).

The MILD procedure.

We are following with great interest the increasing generally favorable impressions of the long-term results of the MILD (minimally invasive lumbar decompression) procedure for treating spinal stenosis due to hypertrophied ligamentum flavum (LF). We are also influenced by the cautionary surgical observations and opinions of Tumialan et al and publications about the lack of efficacy or placebo effect. The impression indeed has been virtual safety of the MILD procedure, but Tumialan et al describe some major complications resulting from the procedure. An algorithm for clinical use is needed.

Prevalence of adverse reactions to radiopaque contrast reported by patients presenting for interventional pain procedure.

INTRODUCTION: Adverse reactions to radiopaque contrast media (RCM) are well documented with a wide range of incidences reported. The objective of this study was to determine how many patients in a sample of 200 who presents for interventional pain treatments report a history of adverse reactions to RCM. METHODS: Data from 200 outpatients were collected using a self-administered questionnaire. The questionnaire was designed to obtain information about prior exposure to RCM and any adverse events plus other general information about allergic reactions including known risk factors for allergic reactions. Demographic data and information about past medical history were obtained from each patient. RESULTS: Of the 200 patients surveyed, 16 reported having had an allergic reaction to RCM. The events met criteria for immediate hypersensitivity reaction. Chemotoxic reactions cannot be ruled out. Of factors associated with risk of allergic reaction, none were clearly more prevalent in subjects reporting an allergic reaction vs. subjects who did not. Atopic patients generally considered susceptible to contrast allergy reported no hypersensitivity reaction. The number of medications and foods the subjects reported caused them to have allergic reactions was extensive. CONCLUSION: Patients with a history suggestive of an immediate hypersensitivity reaction to RCM may report for interventional pain procedures normally performed with RCM. Patients who have experienced an immediate hypersensitivity reaction to RCM have increased risk for another reaction if injected again with contrast agent. Therefore, facilities should be prepared to implement measures to prevent recurrent reactions.

Diagnosis of the vertebral level from which low back or leg pain originates. A comparison of clinical evaluation, MRI and epiduroscopy.

BACKGROUND: The precise localization of painful structures in the spine of patients with low back pain and/or pain radiating (LBP/RP) to the lower extremities is important for targeted therapeutic intervention. The aim of the study reported here was to determine and compare the spinal segment(s) where pain was elicited via endoscopic evaluation vs. the vertebral level from where the pain was thought to originate as determined by clinical evaluation and by MRI. METHODS: Observational cohort study of 143 patients 19 to 88 years of age undergoing spinal canal endoscopy (epiduroscopy) in a combined academic and private practice setting January 2008 to December 2008. Patients were asked whether pain generated by pressure upon epidural structures with the tip of an endoscope was similar in character and distribution (concordant) to the pain for which patients sought treatment. Notes from clinical evaluation and MRI reports were reviewed, and segmental level determined to be the locus of pathology was tabulated. RESULTS: One hundred twenty-five (87%) patients reported maximal reproducible pain at a specific level during epiduroscopy. The most common level was at L4 to L5 (87 patients). The least common level was L5 to S1 (2 patients). In only 40 patients did the level determined by clinical evaluation correlate with the level at which pain could be reproduced during epiduroscopy. MRI indicated a specific vertebral level that corresponded to the level at which pain could be reproduced during epiduroscopy in 28 of 143 (20%) patients. The results of the 3 diagnostic methods were significantly different (P < 0.01). CONCLUSION: Results of this study indicate that epiduroscopy is more reliable than is either clinical evaluation or MRI for determining the vertebral level where clinically significant spinal pathology occurs in patients with LBP/RP.

The story of the Texas Pain Society: formation and function of a regional pain society.

The idea of forming a Texas Pain Society came to the Founders in 1987 due to disparity and deficiencies in the practice of pain management in the United States and, in particular, the State of Texas. The Founders considered very carefully the implication of forming such a society. They diligently mapped out the mission and goals of the Texas Pain Society in those early formative years. This report is the history of Texas Pain Society as the activities unfolded from 1989 to 2011. The reader may question why there is a need to tell such a story. We believe strongly that, with disparities of standards of practice in pain medicine and poor recognition of advances in pain management, this scenario is quite common in many states and countries. The practitioners of pain management in these regions certainly must have considered getting together and forming a consensus on the standards of practice in their communities. This historical report of the Texas Pain Society provides the relevant information necessary and the efforts to be made for a society's mission to achieve its goals and have an ongoing impact in its own region. We hope that we have shed some light on a process for the formation of a regional pain society such as ours.

The peridural membrane of the spinal canal: a critical review.

There exists substantial evidence that a peridural membrane (PM) is present in the spinal canal of humans and, like the pleura and peritoneum, has one or more physiologic functions. Innervation of the PM suggests that it may become a source of pain if injured. Although debated, the physiology of this structure has important implications with respect to neuraxial distribution of drugs and for back and radiating pain. This review, separated into embryological, anatomic, and physiologic discussions, provides an in-depth summary of the observations of this connective tissue. The discrepancies between accounts are highlighted within each section. Focused research to clearly elucidate the true nature of the PM, especially as related to neuraxial distribution of drugs and back and radiating pain, is warranted.

Hyaluronidase: a review of approved formulations, indications and off-label use in chronic pain management.

IMPORTANCE OF THE FIELD: Hyaluronidase for injection is an adjuvant that increases the absorption and dispersion of other injected drugs or fluids (hypodermoclysis); and improves absorption of radiopaque agents in subcutaneous urography. Ovine hyaluronidase is approved for the treatment of vitreous hemorrhages. AREAS COVERED IN THIS REVIEW: We review approved indications for injectable hyaluronidase and off-label uses as well as safety, efficacy and dosing information. We compare formulations made using animal tissue extracts versus the novel human recombinant type. Emphasis is on the human recombinant form and off-label uses in patients with chronic pain. WHAT THE READER WILL GAIN: Hyaluronidase reduces the obstacle that the interstitial matrix presents to fluid and drug transfer. It is a mucolytic enzyme derived from mammalian tissue or synthesized in vitro in pure form (rHuPH20) using recombinant technology. Hyaluronidase is used off-label in chronic pain management to facilitate removal of epidural adhesions with mechanical and/or hydrostatic forces and to treat edema. TAKE HOME MESSAGE: The recently introduced rHuPH20 formulation obviates any risk of allergic reaction or prion-related illnesses. Reduction of edema by hyaluronidase and facilitation of epidural adhesioloysis may be beneficial in treating certain chronic painful conditions.

The effect of levosimendan on bupivacaine-induced severe myocardial depression in anesthetized pigs.

BACKGROUND AND OBJECTIVES: Levosimendan, an inodilator without proarrhythmogenic properties, has been shown to reverse ropivacaine-induced negative inotropy in isolated heart preparations. In this randomized and blinded study, we investigated whether levosimendan is able to reverse rapidly bupivacaine-induced myocardial depression in pigs. METHODS: Twenty invasively monitored pigs anesthetized with isoflurane 1% received bupivacaine 2 mg/kg per minute into a central vein until mean arterial pressure decreased to 55% of baseline. Thereafter, levosimendan 80 microg/kg for 10 mins, followed by 0.7 microg/kg per minute during the next 50 mins (L-SIM) or corresponding amounts of placebo were administered intravenously. Simultaneously, Ringer's acetate was infused intravenously, 20 mL/kg for 10 mins, followed by 20 mL/kg for 50 mins. RESULTS: Two pigs in each group developed cardiac arrest immediately after bupivacaine and could not be resuscitated. Bupivacaine induced widening of the QRS complex in the electrocardiogram and bradycardia.In the remaining 16 pigs, 3 (2 in L-SIM group and 1 in placebo group) needed short-lasting manual cardiac compression and 1 dose of epinephrine. Cardiac output, ejection fraction, and stroke power/end-diastolic volume recovered initially very rapidly in the L-SIM group.However, there was no time x group effect difference in the overall recovery in the various parameters between the 2 groups, except in heart rate which was higher (P G 0.05) when levosimendan was administered.During the 50-min levosimendan infusion, mean arterial pressure and systemic vascular resistance stayed slightly lower in comparison with placebo infusion, but the difference was not statistically significant. CONCLUSIONS: Levosimendan together with the infusion of Ringer's solution rapidly reversed the cardiac depression, but there was no difference in overall cardiovascular recovery in comparison to treatment with Ringer's solution alone. Levosimendan-induced increase in heart rate possibly facilitated the recovery from bupivacaine intoxication.

Incidence and severity of epidural fibrosis after back surgery: an endoscopic study.

BACKGROUND: Epidural fibrosis has been implicated in the etiology of persistent pain after back surgery (Failed Back Surgery Syndrome [FBSS]). Using spinal endoscopy to view the lumbosacral epidural cavity, the incidence, severity, and appearance of epidural fibrosis was evaluated in patients with FBSS. METHODS: A prospective cohort observational study using epidural endoscopy was done involving 78 patients with persistent pain after back surgery. Patients were evaluated prospectively for the presence of epidural fibrosis and fibrosis was rated using a 4-level grading system based on appearance and resistance to epiduroscope advancement. The incidence of fibrosis detected by epiduroscopy vs. the incidence as reported in magnetic resonance imaging (MRI) studies for the same patients were compared. RESULTS: As diagnosed with epiduroscopy, 83.3% of all patients with persistent pain after back surgery had severe (grade 3 or 4) epidural fibrosis, while 91.0% had significant (grade 2, 3, or 4) fibrosis. In patients who had undergone more extensive surgery, severe fibrosis was present in 91.1% and significant fibrosis in 95.6%. Using MRI, epidural fibrosis was diagnosed only in 16.1% of these patients. All patients with severe epidural fibrosis had a filling defect on epidurography. Concordant pain was present in 84.3% of patients and depended on the severity of fibrosis. Results were statistically evaluated using analysis of frequencies and t-test. P < 0.05 was considered statistically significant. CONCLUSIONS: Epiduroscopy demonstrates that the prevalence of severe epidural fibrosis after FBSS is substantially higher than is generally reported in MRI evaluations. Severe epidural fibrosis is an underlying pathology in most patients with FBSS.

Cell types obtained from the epidural space of patients with low back pain/radiculopathy.

BACKGROUND: We investigated if correlations exist between medical history, tissue abnormalities, and cell types retrieved from the epidural space of patients with chronic low back pain (LBP) and chronic radicular pain (RP). METHODS: Approval was obtained from the Institutional Review Board for the Protection of Human Subjects to study 191 patients undergoing epiduroscopy. Visual inspection was performed and abnormal areas were identified. A specimen obtained from the area using a cytology brush was processed by the Thin Prep technique. Patients were divided into four groups based on the presence or absence and intensity of LBP and RP. The gender and age of the patients were recorded, as was any history of prior back surgery. Areas of tissue abnormalities were rated according to changes in vascularity and amount of fat, fibrosis, and inflammation. Stenosis was assessed from magnetic resonance imaging or computerized tomography scan images. Cytologic assessments included notations of the presence or absence of erythrocytes, leukocytes, cell groups, lipocytes, spindled cells, and large round cells. RESULTS: There was a significant difference in the number of patients from whom big round cells were obtained who had a high degree of LBP compared with the number of patients who had a high degree of both LBP and RP. CONCLUSIONS: The findings provide a foundation for future studies of cells obtained from similar patients with the goal of furthering the understanding of the pathogenesis of LBP/RP.