Protectin DX Attenuates Lumbar Radicular Pain of Non-compressive Disc Herniation by Autophagy Flux Stimulation via Adenosine Monophosphate-Activated Protein Kinase Signaling

Background: Neuroinflammation plays a crucial role in initiating and sustaining lumbar radicular pain (LRP). Protectin DX (PDX) has been experimentally verified to possess pro-resolving properties and anti-inflammatory effects. This study aimed to observe the analgesic effects of PDX and its potential mechanisms in LRP rats with non-compressive lumbar disc herniation (NCLDH).Method: Only male rats were selected to avoid gender-related interferences. Rat models of NCLDH were established, and rats were randomly divided into four groups: the sham group, the vehicle group, the PDX (10 ng PDX) group, and the PDX (100 ng PDX) group. Changes in the mechanical withdrawal threshold and thermal withdrawal latency were observed for 7 days. The mRNAs of pro-inflammatory and anti-inflammatory mediators were evaluated via real-time polymerase chain reaction, whereas western blot and immunohistochemistry were separately conducted to assess the expression levels of autophagy-related proteins and adenosine monophosphate-activated protein kinase (AMPK) signaling.Results: Intrathecal delivery of PDX reduced interleukin (IL)-6 and IL-1β mRNA levels and facilitated mRNA transcription of transforming growth factor-β1, with attenuation of mechanical and thermal hyperalgesia in LRP rat models. With the application of nucleus pulposus to the dorsal root ganglion, autophagy flux and AMPK signaling were severely disrupted in the spinal dorsal horns, and intrathecal treatment with PDX could dose-dependently restore the dysfunction of autophagy flux and AMPK signaling.Conclusion: These data suggest that PDX possesses pro-resolving properties and exerts potent analgesic effects in LRP by affecting autophagy flux via AMPK signaling.

Epidural Steroid Injections for Low Back Pain: A Narrative Review

Low back pain represents a significant socioeconomic burden. Several nonsurgical medical treatments have been proposed for the treatment of this disabling condition. Epidural steroid injections (ESIs) are commonly used to treat lumbosacral radicular pain and to avoid surgery. Even though it is still not clear which type of conservative intervention is superior, several studies have proved that ESIs are able to increase patients’ quality of life, relieve lumbosacral radicular pain and finally, reduce or delay more invasive interventions, such as spinal surgery. The aim of this narrative review is to analyze the mechanism of action of ESIs in patients affected by low back pain and investigate their current application in treating this widespread pathology.

Randomized Controlled Trial Comparing the Efficacy and Safety of Epidural Infiltration of Particulate Versus Nonparticulate Steroids in the Treatment of Patients with Sciatic Pain

Introduction: Epidural corticosteroid injections are widely used to treat low back pain, but doubts exist about the relative efficacy of particulate versus non-particulate corticosteroids. Epidural corticosteroid injections were performed in 75 patients with chronic radicular pain were evaluated for epidural corticosteroid injections to determine if there was a difference in the efficacy of triamcilone acetate, methylprednisolone acetate, and dexamethasone. Methods: 75 patients presenting with debilitating radicular pain were randomized to receive an injection of triamcilone acetate 40 mg/ml, methylprednisolone acetate 40 mg/ml, and dexamethasone phosphate 7.5 mg/ml at equal doses. Data were collected at 1-month and 3-month follow-up. The primary outcome of the present study was reduction in pain on a visual analog scale (VAS) at 3 months, while the secondary outcome was the type and number of complications in the study group. Results: Regardless of baseline score VAS, pain score decreased in all patients at one and three months. The patients with VAS of very severe also showed a statistically significant success rate at one and three month follow-up [p= 0.043]. No serious complications occurred in all three groups. Conclusion: According to this study, pain relief and functional improvement are similar among all three methylprednisolone acetate, triamcilone acetate and dexamethasone phosphate at 3 months.

Diagnostic treatment-level discrepancies in patients with lumbosacral radicular pain and lumbar spine anomalies

BackgroundLumbosacral transitional vertebra can result in an anomalous number of lumbar vertebrae associated with wrong level treatment. The primary aim of this study was to characterize discrepancies between reported referring levels and levels from MRI reports with treated levels. The secondary aim was to analyze interobserver variability between a pain physician and a radiologist when determining levels and classifying lumbosacral transitional vertebrae.MethodsBetween February 2016 and October 2019, a retrospective case series of prospectively collected data of the affected levels mentioned in referrals, MRI reports and treated levels was performed. The counting process, level determination, classification of lumbosacral transitional vertebrae and a secondary control were carried out by independent researchers using a standard methodology.ResultsOf the 2443 referrals, 143 patients had an anomalous number of lumbar vertebrae; of these, 114 were included for analysis. The vertebral level noted in the patient’s file, in the referral, and the reported level of treatment differed in 40% of these cases. The vertebral level between the MRI reports and treatment differed in 46% of cases. The interobserver reliability (radiologist vs pain physician) for classifying a transitional vertebra was fair ((κ=0.40) and was substantial (κ=0.70) when counting the vertebrae.ConclusionIn the presence of lumbar spine anomalies, we report a high prevalence of discrepancies between referral levels and MRI pathological findings with treatment levels. Further research is needed to better understand clinical implications.

TNF-ɑ Induces Methylglyoxal Accumulation in Lumbar Herniated Disc of Patients With Radicular Pain

Lumbar disc herniation (LDH) with radicular pain is a common and complicated musculoskeletal disorder. Our previous study showed that LDH-induced methylglyoxal (MG) accumulation contributed to radicular pain. The underlying mechanisms through which MG accumulates are poorly understood. In the present study, we found that both MG and tumor necrosis factor-alpha (TNF-ɑ) levels in the herniated disc of patients with radicular pain were significantly increased, and the activity of Glyoxalase 1 (GLO1), the rate-limiting enzyme that metabolizes MG, was decreased. In rats, the LDH model was mimicked by implantation of autologous nucleus pulposus (NP) to the left lumbar five spinal nerve root. The mechanical allodynia was observed in LDH rats. Besides, MG and TNF-ɑ levels were increased, and GLO1 activity was significantly decreased in the implanted NP. In cultured rat NP cells, stimulation with the inflammatory mediator TNF-ɑ reduced GLO1 activity and expression. These results suggested that TNF-ɑ-induced GLO1 activity decrease contributed to MG accumulation in the herniated disc of patients with radicular pain.

Evaluation of Pre-operational Factors Contributing to a Dorsal Column Stimulator Explantation

Objectives Implantation of a dorsal column stimulator (DCS) for axial spine and radicular pain is a commonly performed procedure. Despite the benefits of this device to reduce pain and improve quality of life, some patients elect to have the device explanted. The purpose of this study is to describe pre-operational factors among patients who elected to have their DCS explanted and how these factors are associated with reason for explantation. Materials and Methods We conducted a retrospective descriptive study using the database of a private outpatient orthopedic clinic. We included all patients who had a dorsal column stimulator explanted between January 1, 2007 and June 19, 2014. Data was collected on patient demographics, past medical and back surgery history, as well as details of implantation, permanent device implantation, and subsequent explantation. Reasons for explantation were categorized as: inadequate pain control using three categories (with no device-related pain/discomfort, with device-related pain/discomfort, or inadequate pain control and patient wants MRI), or pain resolved. Results A consecutive sample of 100 subjects who underwent explantation of a DCS was identified for review. Of these 100 subjects, 14 were excluded. Based on our data, we hypothesize that sex (57% female, 43% male) degenerative disc disease (72%), previous back surgery (70%), BMI classified as overweight (subject average = 28.3), history of tobacco usage (57%), and history of narcotic use (80%) may be potential risk factors for explantation. Conclusions With respect to clinical evaluation of patients as candidates for spinal cord stimulator implantation, we cannot recommend that any of the evaluated variables be considered a contraindication to proceeding with a trial procedure. Future studies are planned to compare these data to a control group of subjects to establish risk factors predisposing individuals to explantation of a DCS. Key words: DCS, neurostimulator, spine, pain, explantation

Headache, Radicular Pain, and Enhancing Lesions

A 37-year-old right-handed woman sought care for a dull headache present for 6 months, which was followed by the development of radicular pain in the left leg radiating down the back of her leg into her foot, with associated left foot numbness. Magnetic resonance imaging of the lumbar spine showed an enhancing lesion within the conus. She was referred for neurosurgical evaluation and underwent magnetic resonance imaging of the entire neuraxis, which showed an enhancing lesion in the left cerebellum. She underwent a left cerebellar debulking surgical procedure. Postoperative diplopia developed for approximately 1 month and then subsequently resolved. She walked with a walker after surgery, with progressive deterioration in gait. Two months after surgery a postural tremor developed in the left arm and leg. She was referred for neurologic evaluation. Pathologic evaluation of cerebellar tissue showed foamy histiocytes and xanthomatous cells that stained positive for CD68 (KP1). Staining for CD1a was negative. Tissue immunohistochemistry for the BRAF V600E sequence variation was negative. No hyponatremia was detected. Positron emission tomography/computed tomography of the body from vertex to toes indicated hypermetabolism in the distal femur and proximal tibia. Examination and imaging findings were consistent with a diagnosis of multifocal Erdheim-Chester disease. The patient was initially treated with pegylated interferon, with clinical and radiographic progression. She was subsequently treated with vemurafenib and dexamethasone, with continued radiologic progression. Treatment with radiotherapy and cladribine were also unsuccessful. At that point, next-generation sequencing of cerebellar tissue showed a BRAF V471F sequence variation. She was then treated with trametinib, which resulted in a decrease in size of the cerebellar lesion and growth stabilization of the conus lesion. Histiocytic neoplasms are a heterogeneous group of multisystem disorders, primarily including Erdheim-Chester disease, Langerhans cell histiocytosis, and Rosai-Dorfman disease. Although initially thought to represent inflammatory processes, recent insights into their genomic architecture have shown that they are derived from macrophage-lineage neoplasms.

Spontaneous regression of a large sequestered lumbar disc herniation: a case report and literature review

Lumbar disc herniation is a common disorder in adults that is accompanied by lower back and radicular pain. A 32-year-old man visited our clinic with 1-week history of persistent lower back pain and weakness in his right big toe. Magnetic resonance imaging (MRI) of his lumbar spine revealed herniated discs at L3/L4, L5/S1 and L4/L5, where a right-sided intraspinal mass lesion deep to the L4 vertebral body was causing compression of the nerve root. The patient underwent conservative treatment and reported no symptoms referrable to his back or leg 4 months later. Follow-up MRI showed no herniation of the nucleus pulposus at the L4/L5 level or lesion deep to the vertebral body of L4, whereas no changes had occurred to the status of the herniated L3/L4 and L5/S1 discs. The present case and a literature review show that a sequestered lumbar disc herniation can regress within a relatively short timeframe without surgery. The authors emphasise the utility of conservative therapy for patients who do not have a definitive surgical indication.