Efficacy of PLDD Versus ESI in the Treatment of Lumbar Radicular Pain

Study Overview
=================
Brief Summary
-----------------
The most common cause of lumbar radicular pain is intervertebral disc herniation with or without pressure on the nerve root, which leads to inflammation and pain. Just as the mechanical component is important, so is the inflammatory component in the etiology of lumbar radicular pain. Numerous pro-inflammatory and anti-inflammatory proteins were found in serum, cerebrospinal fluid and disc biopsies from patients with lumbar radicular pain. Interleukin(IL)-1β, IL-6, IL-8, and tumor necrosis factor TNF-α are the most frequently investigated (8, 9). Elevated levels of IL-6 and TNF-α were found in patients with lumbar pain caused by intervertebral disc herniation. In order to avoid systemic and unwanted effects of analgesics, undergoing anesthesia and long-term and extensive operations, minimally invasive procedures are increasingly used in the treatment of lumbar radicular pain. Epidural administration of steroids and local anesthetic through a transforaminal approach (ESI TF) and percutaneous laser disc decompression (PLDD) are some of these methods. Lumbar radicular pain occurs due to inflammation and/or disc-radicular contact. Corticosteroids interrupt the inflammatory process, the transmission of pain signals via nociceptive C fibers and reduce capillary permeability. Along with the corticosteroid, a local anesthetic is also applied, which leads to immediate analgesia by blocking the conduction of painful impulses by blocking sodium channels. Percutaneous laser disc decompression (PLDD) is a minimally invasive method of treating lumbar radicular pain performed under local anesthesia under fluoroscopic control. The laser energy leads to the heating of the tissue of the nucleus pulposus, which leads to the evaporation of a small volume of water inside the disc. Viewing the disc as a closed hydraulic system, a small decrease in the water content within the disc leads to a disproportionate decrease in intradiscal pressure, which results in retraction of the herniated disc. Thermal energy leads to protein denaturation, which causes structural changes and thus prevents further retention of water in the disc, and a stable scar is created at the point of laser action. On the basis of current knowledge, an attempt is made to establish a link between inflammatory parameters as predictive and prognostic biomarkers in the treatment of patients with lumbar radicular pain caused by intervertebral disc herniation.

Detailed Description
-----------------
The hypothesis is that: there will be no difference in effectiveness in reducing the intensity of pain, improving the quality of life, reducing the degree of disability, reducing neuropathic pain, reducing anxiety and depression, and improving the quality of sleep in the treatment of lumbar radicular pain caused by disc herniation without discoradicular contact, but PLDD will be more effective in patients where there is discorradicular contact PLDD will lead to a greater reduction in serum levels of inflammatory markers in patients with nerve compression by intervertebral disc herniation ESI TF will lead to a greater reduced serum level of inflammatory markers where there is no nerve compression by intervertebral disc herniation The group of patients in whom PLDD was performed will have a significantly greater retraction of the disc herniation compared to ESI TF

Official Title
-----------------
Efficacy of Percutaneous Laser Disc Decompression Versus Epidural Steroid and Local Anesthetic Injection by Transforaminal Approach in the Treatment of Lumbar Radicular Pain

Conditions
-----------------
Herniated Disc, Low Back Pain

Intervention / Treatment
-----------------
* Procedure: Epidural Steroid Injection
* Procedure: Percutaneous Laser Disc Decompression


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 and 60 Signing informed consent Unilateral lumbar radicular pain Subjects who do not responds to conservative treatment Disc herniation at one level MR verified disc herniation Pain intensity measured by VAS scale, from 0 - 10, >5 Exclusion Criteria: Subjects younger than 18 and older than 65 years Refusal of the subjects to participate in the research Central stenosis of the lumbar canal Lumbar radicular pain caused by causes other than intervertebral disc herniation Pregnancy Allergy to steroids, local anesthetics, fentanyl, midazolam and contrast medium Positive history of prolonged bleeding Local or systemic infection Previous lumbar spine surgery7 Opioid abuse Proven inflammatory rheumatic disease and inflammatory bowel disease in the active phase Other acute infections

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The research is designed as a randomized controlled trial, and will be conducted at the Clinic for Anesthesiology, Reanimatology and Intensive Medicine in the Department of Pain Management of the Osijek Clinical Hospital Center after obtaining the approval of the Ethics Committee. All patients will receive a written informed consent in which the procedure to be performed will be described, and the procedure will also be explained to them orally. After signing the informed consent, the patients will be divided into 2 groups using a random number generator, depending on whether there is discorradicular contact or not, and then according to the treatment method (ESI TF or PLDD). All subjects will be selected at the Institute for Pain Management of KBC Osijek.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Discoradicular contact+ESI TF<br>Patients with discorradicular contact who underwent ESI TF | Procedure: Epidural Steroid Injection<br>* Epidural Steroid Injection transforaminal approach Drug: midazolam, fentanyl, lidocaine, levobupivacaine, methilprednisoloneacetat<br>|
| Active Comparator: Discoradicular contact+PLDD<br>Patients with discorradicular contact who underwent PLDD | Procedure: Percutaneous Laser Disc Decompression<br>* Percutaneous Laser Disc Decompression Drug: midazolam, fentanyl, lidocaine<br>|
| Active Comparator: Without discoradicular contact+ESI TF<br>Patients without discorradicular contact who underwent ESI TF | Procedure: Epidural Steroid Injection<br>* Epidural Steroid Injection transforaminal approach Drug: midazolam, fentanyl, lidocaine, levobupivacaine, methilprednisoloneacetat<br>|
| Active Comparator: Without discoradicular contact+PLDD<br>Patients without discorradicular contact who underwent PLDD | Procedure: Percutaneous Laser Disc Decompression<br>* Percutaneous Laser Disc Decompression Drug: midazolam, fentanyl, lidocaine<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the effectiveness in reducing pain intensity with ESI TF and PLDD in patients with lumbar radicular pain caused by intervertebral disc herniation | Compare the effectiveness in reducing pain intensity with epidural administration of steroids and local anesthetic through a transforaminal approach (ESI TF) and percutaneous laser disc decompression (PLDD) in patients with lumbar radicular pain caused by intervertebral disc herniation, measured by the VAS scale (0-10). The severity of pain was assessed using the visual-analog scale of pain (VAS). The scale consists of a solid line that is 0 to 10 numbered at both its beginning and conclusion. The number 0, which denotes the lack of pain, is located on the far left, while the number 10, which denotes unbearable pain, is located on the far right. | Six months | 
| Investigate the difference imeasured with a visual analogue scale between ESI TF and PLDD in herniated intervertebral disc with and without discoradicular contact | Investigate the difference measured with a visual analogue scale between ESI TF and PLDD in herniated intervertebral disc with and without discoradicular contact. The severity of pain was assessed using the visual-analog scale of pain (VAS). The scale consists of a solid line that is 0 to 10 numbered at both its beginning and conclusion. The number 0, which denotes the lack of pain, is located on the far left, while the number 10, which denotes unbearable pain, is located on the far right. | Six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate the influence of ESI TF and PLDD on the serum level of interleukin-6 (IL-6) | Investigate the influence of ESI TF and PLDD on the serum level of interleukin-6 (IL-6) | Six months | 
| Investigate the impact of PLDD and ESI TF in the treatment of lumbar radicular pain caused by disc herniation on quality of life | Investigate the impact of PLDD and ESI TF in the treatment of lumbar radicular pain caused by disc herniation on quality of life measured by SF-36 (Short form health survey-36). The Health Status Questionnaire SF-36 was used to examine health status and health-related quality of life. The questionnaire is intended for self-assessment of mental and physical health and social functioning. The SF-36 is a short health status questionnaire consisting of 36 questions. The score is expressed as a standardized value ranging from 0 to 100 for each dimension. Low scores reflect reduced and limited functionality, i.e. loss of function, existence of pain and poor health assessment. High scores reflect the assessment of health as good, without pain and without functional limitations. | Six months | 
| Investigate the influence of PLDD and ESI TF on the retraction of disc herniation | Investigate the influence of PLDD and ESI TF on the retraction of disc herniation which will be measured by MR control after 6 months | Six months | 
| Investigate the impact of PLDD and ESI TF in the treatment of lumbar radicular pain caused by disc herniation on degree of disability | Investigate the impact of PLDD and ESI TF in the treatment of lumbar radicular pain caused by disc herniation on degree of disability measured by Oswestry Disability Questionnaire Index (ODI). The degree of disability for carrying out everyday activities as a result of low back pain will be evaluated using the Oswestry Disability Index (ODI) questionnaire. The domains of the questionnaire cover aspects of pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sexual function, social life, and traveling, each one containing six statements about section-related activities. The responses are scored on a 0-5 scale. Total score is expressed as the percentage of the maximum score with lower scores indicating lower levels of disability and vice versa. | Six months | 
| Investigate the impact of PLDD and ESI TF in the treatment of lumbar radicular pain caused by disc herniation on neuropathic pain | Investigate the impact of PLDD and ESI TF in the treatment of lumbar radicular pain caused by disc herniation on neuropathic pain measured by Pain Detect. The Pain Detect questionnaire is a standardized questionnaire for screening the probability of the existence of a neuropathic pain component in patients with chronic pain. It consists of three parts in sequence from the assessment of the intensity of the pain through the pictorial presentation of the nature of the pain and the main area of the pain to the final questions about the severity of the sensory symptoms which are classified into five groups according to the intensity, from never to very severe. | Six months | 
| Investigate the impact of PLDD and ESI TF in the treatment of lumbar radicular pain caused by disc herniation on degree of anxiety and depression | Investigate the impact of PLDD and ESI TF in the treatment of lumbar radicular pain caused by disc herniation on degree of anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS). The HADS questionnaire has seven items each for depression and anxiety subscales. Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. A total subscale score of >8 points out of a possible 21 denotes considerable symptoms of anxiety or depression. | Six months | 
| Investigate the impact of PLDD and ESI TF in the treatment of lumbar radicular pain caused by disc herniation on quality of sleep | Investigate the impact of PLDD and ESI TF in the treatment of lumbar radicular pain caused by disc herniation on quality of sleep measured by the Pittsburgh Sleep Quality Index (PSQI), consisting of 19 items, each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. | Six months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
herniated disc, epidural injection, laser, low back pain, radiculopathy