Impact of Transforaminal Epidural Steroid Injection in Lumbar Disc Prolpse on Micro RNA-155 Serum Level

Lumbar Disc Herniation Clinical Trial

Official title: Transforaminal Epidural Steroid Injection in Lumbar Disc Prolapse: Impact on Pain and Cognition in Relation to Micro RNA-155 Serum Level

Status Completed

Clinical Trial Summary

Lumbar disc prolapse is a common cause of disabling Low back pain. The prevalence of disc prolapses or herniation in the general population increases with age. The underlying mechanism of pain is related to a complex interaction between inflammatory, compressive and immunological factors. The pressure exerted by the prolapsed disc on the longitudinal ligaments and the irritation caused by the released inflammatory chemokines results in localized back pain. The lumbar disc-related radicular pain arises when the prolapsed disc exerts pressure on the thecal sac or lumbar nerve roots, resulting in nerve root inflammation and ischemia. Chronic pain has been associated with poor cognitive functions in multiple domains, especially in the older population. Significant cognitive dysfunction has been reported in the domains of memory, executive functioning, attention abilities, psychomotor and processing speeds. Also, chronic pain was associated with physical limitations in walking speed and activities of daily living. MicroRNAs (miRNAs) are small endogenous RNAs that repress gene expressions post-transcriptionally. They are involved in the processes of neuropathic pain regulation through targeting the 3'UTR of mRNAs. miR-155 is a multifunctional miRNA, being a fundamental regulatory factor in immune response, neuro-inflammation, cognitive impairment and neuropathies. Previous studies suggest evidence that miRNA-155 promotes the release of pro-inflammatory mediators and cytokines that may alter neuronal sensitivity and modulate nerve plasticity, causing neuropathic pain. miR-155 also has a role in inflammatory reactions and targeting inflammation-related proteins such as serum and glucocorticoid-regulated protein kinase 3 (SGK3). Transforaminal epidural steroid injection (TFESI) is a common intervention for the treatment of neuropathic pain related to disc prolapse. Steroids inhibit the production of several proinflammatory mediators, leading to the reduction of nerve root inflammation induced by mechanical compression. Further, it can block neural transmission through nociceptive nerve fibres. A paucity of data is available about the effect of the different therapeutic modalities of lumbar disc-related radicular or low back pain on the pain-related functional and structural brain alterations and the associated cognitive dysfunction This study is designed to evaluate the impact of TFESI in lumbar disc prolapse on pain intensity, cognitive function, and miR-155 serum level. The second objective was to study the relationship between pain intensity, cognitive function, and miRNA-155 serum level in patients with lumbar disc prolapse.

Clinical Trial Description

Study design and Participants In this case-control study, 44 patients diagnosed with symptomatic lumbar disc prolapse (L4-L5) and another 44 age and sex-matched healthy volunteers were evaluated. Patients were recruited from the neurology and pain management outpatient clinics at Beni-Suef University Hospital during the period from December 2022 to September 2023. The healthy controls were recruited from the patients' relatives. They should be free from any medical illness known to cause pain or impact cognition. The study was registered in ClinicalTrials.gov on 19/11/2022 (the identification number is NCT05626283). This study included patients with clinical and radiological evidence of L4-L5 disc prolapse manifesting as radicular pain and/or low back pain unresponsive to medical treatment and physiotherapy over a period of at least three months. Exclusion criteria included patients with severe lumbar disc prolapse affecting motor or sphincteric functions, history of spinal surgery, spinal trauma, spinal deformities, spinal neoplasm or any spinal inflammatory lesion, hip osteoarthritis or sacroiliitis. Also, patients with medical disorders known to cause cognitive impairment and pregnant women were excluded. The study was conducted in two stages. In the first stage, baseline serum levels of miR-155 and cognitive assessments were performed for both patients and control groups. Further, at this stage, the patients' group was evaluated regarding pain intensity and functional disability. Demographic data and the duration of lumbar disc-related radicular pain were obtained. The second stage was carried out one month after TFESI, in which the patients' group (n=44) who had symptomatic lumbar disc prolapse were evaluated regarding miR-155 serum level, pain intensity, functional disability, and cognitive testing to explore the effect of steroid injection on these variables. Pain intensity and functional disability 1. Numeric Rating Scale (NRS) It is an 11-point numeric scale for pain intensity evaluation, ranging from 0 to 10, where higher scores denote more intense pain. 2. Oswestry Disability Index (ODI) It is a scale used to measure functional incapacity from low back pain across many aspects including lifting, walking, standing, sitting, personal care, sleeping, travelling, work and social life. It consists of ten questions, scored on a scale of 0-5 for each, where higher scores denote more limitations. After the summation of all these subscores, the result is multiplied by two to gain the index (ranging from 0 to 100). 3. Functional rating index (FRI) Another scale was used to weigh functional limitations in daily activities in people with low back pain. The scale consists of 10 items scored on a scale of 0-4 for each, where higher scores denote more disability. Cognitive assessment Paired Associate Learning test (PALT) This test was used to assess episodic verbal memory. Six semantically related word pairs and unrelated four pairs were introduced to the subject. After that, the patient was requested to retrieve the word that was paired with each word. The test was conducted on three trials. A score of 0.5 is given for each true well-matched pair, while a score of 1 is given for each true mismatched pair, with a total score ranging between 0 and 21. Paced Auditory Serial Addition Test (PASAT) This test was used to assess attention and processing speed. A set of single digits is audio recorded at a rate of one every 3 seconds and then introduced to the subject. The subject was requested to add each digit to the one just heard before. The number of correct answers was summed to gain the total score (0 to 60). Controlled Oral Word Association Test (COWAT) It is a verbal fluency test that assesses executive function. The subject was inquired to generate words that begin with a specified letter in one minute, eliminating proper nouns. Interventional pain Procedure (transforaminal epidural steroid injection) In the preparation room, the patient was placed in a prone position on a fluoroscopy table and draped in a sterile manner. The patient was connected to a monitor (BP, SPO2, and ECG) and given supplemental oxygen through a nasal cannula (3 L/min). Under fluoroscopic guidance, a spinal needle (a 22-gauge, 3.5-inch) was advanced in an oblique view. To access the safe triangle, the classic Scottie dog view was obtained and the needle was directed toward the inferior-lateral boundary of the pedicle. To confirm the appropriate location of the needle, both lateral and anterior-posterior views were obtained. With each insertion of the spinal needle, 1 ml with 20 mg of local anaesthetic lidocaine 2% was injected intradermally. The transforaminal epidural injection of steroids with local anaesthetic [triamcinolone acetonide 40 mg (1 mL) and Bupivacaine hydrochloride 0.5% (3 mL)] Laboratory assessment Real-time PCR evaluation of miRNA 155 by quantitative reverse transcription (q RT) Sample collection One venous blood sample was collected from each of the forty-four healthy controls, while two samples were obtained from each of the forty-four patients with lumber disc prolapse; first, a baseline sample followed by a second one a month after steroid injection. Extraction, purification, and transcription According to the manufacturer's protocol, serum RNA was extracted using miRNeasy Kit (Catalog number 217184, Qiagen). Transcription of miRNA into complementary DNA (cDNA), by miScript II RT Kit, (catalogue number 218161, Qiagen) was performed under the following conditions: incubation of 20 μl reverse transcription reaction for 60 minutes at 37°C, followed by 5 minutes at 95°C to stop the Reverse Transcriptase. 200 μl RNase-free water was used to dilute cDNA. Complementary DNA was stored at -80°c till PCR processing. Real-time PCR detection and relative quantification (RQ) In the qRT-PCR assay, specific forward primers with Qiagen catalog numbers; MS00031486 for microRNA 155 and MS00033712 for SNORD-68 (endogenous control), were used along with the Qiagen reverse universal primer, and the Syber Green PCR Master Mix according to the manufacturer's instructions. Real-time PCR thermal cycles included an initial non-repetitive activation step at 95°C for 15 minutes followed by forty repeated cycles. Each cycle comprised 3 main steps: denaturation at 94°C for 15 seconds, annealing at 55°C at 30 seconds in addition to extension for 30 seconds at 70°C. Relative quantification of miRNA 155 was performed by using the 2-ΔΔ Ct equation (comparative method, or ΔΔCT method) (Livak,2001). Normalization was achieved by using SNORD 68 as an internal control. ;

Related Conditions & MeSH terms

• Intervertebral Disc Displacement
• Lumbar Disc Herniation

• NCT number: NCT05626283
• Study type: Interventional
• Source: Beni-Suef University
• Status: Completed
• Phase: Phase 4
• Start date: December 1, 2022
• Completion date: September 1, 2023