Chronic pain could be considered a brain disease as it can affect multiple aspects of brain function, chemistry, neural networks and structure. Pain is associated with impaired cognitive function (1). Around 45-50% of these patients report cognitive deficits such as forgetfulness (23.4%), minor accidents (23.1%), difficulty finishing tasks (20.5%), and difficulty maintaining attention (18.7%) (2,3). Many studies emphasized an impairment in the cognitive tests assessing executive functioning, attention abilities, processing speed, and memory in patients with chronic pain (4,5). Studies of community-dwelling older adults found that pain, particularly widespread or severe pain, was associated with mobility Limitations in physical performance (e.g., walking speed, stair climbing, and activities of daily living) (6-9) in individuals with chronic pain and correspond to the pain level (10,11). Finally, both pain and impaired cognition affect mobility status in older adults, and mobility is affected to a greater extent when both are present (12). Recent data indicate that miR-155 has a typical multifunctional miRNA and plays a crucial role in various physiological and pathological processes such as immunity, inflammation, cognitive dysfunction and neuropathies (13). The available experimental evidence indicating that miR-155 is up-regulated in neuropathies allows us to include this miRNA in the list of genes of paramount importance in chronic low back pain diagnosis and prognosis. Exogenous molecular control in vivo of miR-155 expression could open up new ways to restore cognitive outcome or attenuate the pain intensity (14). No study searched the role of intervention (epidural steroid injection) on cognitive function reserve, whether it is a better substitution or not for the conservative medical treatment. Since exogenous steroid is a part of epidural injection, the systemic effect of a single dose of steroids does not affect cognitive function, giving superiority to the intervention modality on the conservative medical therapy approach (15). Aim of the work This work aims to study the impact of transforaminal epidural steroid injection in lumbar disc prolapse on pain intensity and cognitive function in relation to Micro RNA-155 serum level.
Full Title of Study: “Transforaminal Epidural Steroid Injection in Lumbar Disc Prolpse: Impact on Pain Intensity and Cognitive Function in Relation to Micro RNA-155 Serum Level”
- Study Type: Interventional
- Study Design
- Allocation: Non-Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: Single (Investigator)
- Study Primary Completion Date: April 1, 2023
Study design and Participants: The study will be conducted in two stages: Stage (1): It will be a case control study that will include 46 patients diagnosed as having symptomatic lumbar disc prolapse and 46 age and sex matched healthy controls. Both patients and control groups will be subjected to measurement of baseline miR-155 expression level. Stage (2): It will be an interventional non-experimental study that will include only the 46 patients who had symptomatic lumbar disc prolapse. Those patients will be subjected to transforaminal epidural steroid injection. Assessment of pain intensity, functional disability, cognitive function, depression, and miR-155 expression level will be done for the included patients before and 1 month after transforaminal epidural steroid injection to clarify the effect steroid injection on these variables. The included patients will be recruited from the neurology and pain clinics of Beni-Suef University Hospital, in the period from August 2022 to August 2023. Eligibility criteria: The study will include patients with clinical evidence of disc bulge in the form of disc related radicular pain of >3 months duration, not responding to conservative treatment and interfering with daily activities. The selected patients should have radiological evidence of posterolateral lumbar disc bulge by MRI lumbosacral. The following patients will be excluded from our study: patients with a history of spinal trauma, spinal surgery or spinal deformities, patients with radiological evidence of any inflammatory or neoplastic lesion affecting the vertebral column or spinal cord, patients with facet or hip osteoarthritis or sacroiliitis, patients with severe lumbar disc prolapse causing lower limb weakness or sphincteric troubles, patients with contraindications to interventions (sepsis, coagulopathy, or allergy from the used drugs), and patients with central or metabolic disorder known to cause cognitive dysfunction. Pregnant patients will be also excluded from our study. Data collection History will be taken from the selected patients regarding the demographics and the duration of lumbar disc related radicular pain. The imaging findings regarding the number of prolapsed discs and the degree of the most prolapsed disc will be also obtained. Assessment of pain intensity and functional disability Assessment of the pain intensity and functional disability will be done before and 1 month after the interventional pain management procedure. Assessment will be done using Numeric Rating Scale (NRS) and Oswestry Disability Index (ODI). Numeric Rating Scale (NRS) is a single 11-point numeric scale for assessment of intensity of pain. It ranged from 0 to 10, where 0 indicates no pain and 10 indicates the worst pain.  Oswestry Disability Index (ODI) is a questionnaire used to quantify the disability from low back pain. It includes the following items: pain intensity, the level of disability of personal care, lifting, walking, sitting, standing, sleeping, traveling, sexual and social life. Each question is scored on a scale of 0-5 with 0 representing no limitation, and 5 representing maximal limitation. The scores for all questions answered are summed, then multiplied by two to obtain the index (range 0 to 100).  Cognitive assessment Cognitive assessment will be done before and 1 month after the interventional pain management procedure. Assessment will be done using Paired Associate Learning test (PALT), Paced Auditory Serial Addition Test (PASAT), and Controlled Oral Word Association Test (COWAT). Paired Associate Learning test (PALT) will be used to assess auditory verbal memory. In this test, the examiner says 6 semantically related pairs of words and 4 semantically unrelated pairs. After few minutes, the examiner says the first word of each of these pairs to the patient, and the patient was asked to recall the other word. The test must be performed three times. Each correct compatible pair takes a score 0.5, while each correct incompatible pair takes a score 1. The range of the total score was between 0 to 21.  Paced Auditory Serial Addition Test (PASAT) will be used for assessment of attention and auditory working memory. In this test, a series of 61 single digit numbers are spoken on an audiotape (or CD) at a rate of one every 3 seconds. The subject is asked to add each number to the one immediately preceding it and not to give a running total. The subject has to report the sum orally. Total score is the sum of correct responses and it ranges from 0 to 60.  Controlled Oral Word Association Test (COWAT) is a verbal fluency test that assess attention and executive function. The participant is usually asked to name words beginning with a letter, excluding proper nouns, for one minute.  Assessment of depression Assessment of depression will be done before and 1 month after the interventional pain management procedure using Beck depression inventory (BDI). It is a self-rated questionnaire consisting of 21 items, in which four response options are presented on a scale of 0 to 3.  Interventional pain Procedure: The selected patients will be brought to the preparation room where reassurance will be done. Intravenous midazolam 0.2 mg/kg will be given to them, then they will be placed in the prone position on fluoroscopy table and draped in a sterile manner. They will be connected to a monitor (SPO2, NIBLP, and ECG) and given supplemental oxygen through a nasal cannula (3 L/min) to maintain the oxygen saturation. A 22-gauge, 3.5-inch spinal needle will be used in the injection procedure. With each insertion of the spinal needle, 1 ml with 20 mg of local anesthetic lidocaine 2% will be injected intradermally. The patients will be given transforaminal epidural injection of steroids with local anesthetic (7 mg Betamethasone preceded by a test dose of 1 milliliter 2% lidocaine). Laboratory assessment Estimation of miR-155 expression level: Blood samples (5 mL) will be collected from the patients (before and 1 month after the interventional procedure) and controls. The samples will be centrifuged at 3000 rpm for 10 min and plasma and/ or serum will be stored at -80 C till analysis. Total RNA will be extracted. Quantitative real-time polymerase chain reaction (PCR) will be performed. miR-155 expression level will be calculated by the difference in threshold cycle method.
- Drug: transforaminal epidural injection.
- transforaminal epidural steroid injection.
- Other: micro RNA-155 serum level
- Estimation of miR-155 expression level:
Arms, Groups and Cohorts
- Active Comparator: lumbar disc prolapse group
- 46 patients diagnosed as having symptomatic lumbar disc prolapse
- Placebo Comparator: Control
- 46 age and sex matched healthy controls
Clinical Trial Outcome Measures
- Assessment of pain intensity
- Time Frame: 1 month
- Change in Numeric Rating Scale (NRS)
- Assessment of functional disability
- Time Frame: 1 month
- Change in Oswestry Disability Index (ODI)
- Assessment of miR-155 expression level
- Time Frame: 1 month
- Change in miR-155 expression level
- Memory assessment
- Time Frame: 1 month
- Change in Paired Associate Learning test (PALT)
- Attention assessment
- Time Frame: 1 month
- Change in Paced Auditory Serial Addition Test (PASAT)
- Assessment of depression
- Time Frame: 1 month
- Change in Beck depression inventory (BDI).
Participating in This Clinical Trial
- Patients with clinical evidence of disc bulge in the form of disc related radicular pain of >3 months duration, not responding to conservative treatment and interfering with daily activities. – The selected patients should have radiological evidence of posterolateral lumbar disc bulge by MRI lumbosacral. Exclusion Criteria:
- Patients with a history of spinal trauma, spinal surgery or spinal deformities. – Patients with radiological evidence of any inflammatory or neoplastic lesion affecting the vertebral column or spinal cord. – Patients with facet or hip osteoarthritis or sacroiliitis. – Patients with severe lumbar disc prolapse causing lower limb weakness or sphincteric troubles. – Patients with contraindications to interventions (sepsis, coagulopathy, or allergy from the used drugs). – Patients with central or metabolic disorder known to cause cognitive dysfunction. – Pregnant patients will be also excluded from our study.
Gender Eligibility: All
Minimum Age: 20 Years
Maximum Age: 80 Years
Are Healthy Volunteers Accepted: Accepts Healthy Volunteers
- Lead Sponsor
- Beni-Suef University
- Provider of Information About this Clinical Study
- Principal Investigator: Mona Hussein, Associate professor of Neurology – Beni-Suef University
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