Effect of Pulsed Mode Radiofrequency as a Treatment of Lumbar Disc Related Radicular Pain on Tumor Necrotic Factor α Level
Condition: Lumbar Disc Herniation
MeSH terms: Intervertebral Disc Displacement
Study type: Interventional
Phase: Phase 1

Summary: 
      Lumbar radiculopathy is a term that describes symptoms of pain, numbness, and/or weakness
      that radiate along the sciatic nerve from the lower back to the buttocks and leg (1). Lumbar
      radiculopathy is a relevant health problem that affects quality of life, resulting in high
      health costs and economic loss worldwide (2). The reported prevalence of sciatica varies
      widely from 1.2% and 43% in the general population (3).

      Although initially believed to be a primary mechanical insult to the nerve root and dorsal
      root ganglion, lumbar radiculopathy is possibly caused by inflammatory changes in the nerve
      root (4). The role of cytokine-mediated neuroimmune interactions in the development and
      persistence of pain has been extensively studied (5,6,7).

      Intraneural application of pro-inflammatory cytokines induces behavioral signs associated
      with pain (8). Anti-inflammatory cytokine treatment effectively reduces hyperalgesia (9).
      Inflammatory cytokine inhibitors provided long-lasting analgesia in an inflammatory
      neuropathic pain model. On the basis of these findings, we evaluated whether cytokine
      profiles differ between severe and mild human sciatica, as well as whether distinct cytokine
      profiles provide relevant information regarding lumbar radiculopathy pathogenesis. (10,11).

      Tumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine that can stimulate inflammatory
      responses of synapses and myelin sheath, promote cellular apoptosis because of its cytotoxic
      effect, and induce nerve swelling and neuropathic pain (12).

      TNF-α influences neural survival, exerting both neuroprotective and neurodegenerative actions
      (13). Following peripheral nerve injury, upregulation of TNF-α expression has been documented
      in several neuropathic pain models (14).

      Pulsed radiofrequency (PRF) is a relatively new developed technique that is a variation of
      conventional radiofrequency treatment. PRF treatment does not allow temperatures above 42°C
      at the tip of the electrode. PRF provides advantage avoiding thermal tissue destruction and
      pain sequelae in management of pain. Recently, it has been recommended for treatment of
      chronic pain (15).

      Electromagnetic field which is thought to be responsible for the clinical effect of pulsed RF
      spread from active tip of electrode to around the electrode. The most intense part of the
      electromagnetic field is pointed tip of the electrode (16). It is a minimally invasive
      technique that involves application of electric fields to nerves to inhibit nociceptive
      stimuli and prevent pain transmission. PRF can be considered when conventional treatments
      have intolerable side effects or do not sufficiently relieve pain (17).

      Working mechanism of PRF which is recently more preferred technique to treat chronic pain due
      to not forming tissue damage and less painful procedure is not exactly known but it is
      considered to act neuromodulation (18).

      The aim of this work is to compare the effect of transforaminal injection of Steroids alone
      versus Radiofrequency pulsed mode on dorsal root ganglion combined with transforaminal
      steroids injection on TNF-α level in lumbar disc related radicular pain
    

Detailed description: 
      This is a prospective randomized controlled trial that will be carried out on 80 patients
      diagnosed as having symptomatic lumbar disc prolapse.

      The study will be planned by taking the local ethics committee approval and patients' written
      consent. Between 20-75 years of age, 40 patients will receive pulsed radiofrequency on dorsal
      root ganglion combined with transforaminal steroids injection procedure and 30 patients will
      receive transforaminal steroid injection. All patients are suffering more than 3 months long
      chronic pain syndrome.

      Patients will be informed about the technique, at the level of cooperation that can provide
      this information to understand and work with patients who have the level of cooperation that
      can provide this information to understand and agree to participate in work will be included
      in the study. Patients included in the study will be given an appointment for the procedure
      and Written consent will be obtained from all participants .The patients will be recruited
      from the neurology and pain clinic of Beni-Suef University Hospital, in the period from March
      2022 to September 2022.

      Inclusion criteria:

      Patients diagnosed as having symptomatic lumbar disc prolapse based on the following:

        1. Clinical evidence of disc pulge in the form of disc related radicular pain of >3 months
           duration, not responding to conservative treatment and interfering with daily activities

        2. Radiological demonstration of posterolateral lumbar disc pulge by MRI lumbosacral

        3. Age range is between 30-80 years

      Exclusion criteria:

      The following patients will be excluded from the study:

        1. Patients with spinal deformities

        2. Patients with a previous history of spinal trauma

        3. Patients with previous spinal surgery

        4. Patients with radiological evidence of any inflammatory or neoplastic lesion affecting
           the spinal cord or vertebral column

        5. Patients with severe lumbar disc herniation causing lower limb weakness or sphincteric
           troubles

        6. Patient with pain rather than radicular neuropathic pain as Facet osteoarthritis,
           Sacroiliitis, Hip osteoarthritis, Discogenic, Pyriformis syndrome.

        7. Patients with contraindications to interventions (coagulopathy, sepsis, or allergy to
           the used drugs)

        8. Patients with contraindications for MRI examination (e.g., metallic implants such as
           pacemakers, surgical aneurysm clips, or known metal fragments embedded in the body).

        9. Pregnant

       10. History of G6PD deficiency in patients who are candidates to receive ozone therapy.

       11. Suspected spondylodiscitis.

      METHODS:

      All patients will be subjected to the following:

      1) Clinical assessment:

        1. Detailed history taking regarding: duration of pain, the presence of discogenic pain,
           radicular pain, responseto medical treatment, or previous interventional pain management

        2. Neurological examination: motor and sensory examination

        3. Assessment of the severity of the neurological symptoms before and 2 weeks,1 and 3
           months, after the interventional procedure by a physician who will be blinded to the
           type of intervention.

           Modified Oswestry Back Disability Score (MODI): It consisted of low back pain disability
           index questionnaire about pain intensity, personal care, lifting, standing, walking,
           sitting, sleeping, social life, travelling and employment/homemaking. Thus, total 10
           points; each had score range of 0-5. Hence, total score had range of 0-50. A high MODI
           score indicates a more severe functional disability related to the pain.

           Numeric Rating Scale (NRS-11): It is a scale for assessment of intensity of pain. It
           ranged from 0 to 10, where 0 indicates no pain and 10 indicates the worst pain.

        4. Assessment of patient's satisfaction about the intervention 3 months after the
           interventional procedure by a physician who will be blinded to the patient's condition
           and the type of intervention.

      The Short Assessment of Patient Satisfaction (SAPS): It consists of seven items assessing the
      core domains of patient satisfaction which include treatment satisfaction, explanation of
      treatment results, clinician care, participation in medical decision making, respect by the
      clinician, time with the clinician, and satisfaction with hospital/clinic care. Responses
      scales are 5-point scales. SAPS scores can be interpreted as follows: 0 to 10 = very
      dissatisfied, 11 to 18 = dissatisfied, 19 to 26 = satisfied, 27 to 28 = very satisfied.

      2) Laboratory assessment: Blood samples will be collected for all included patients in a
      fasting state, before and three months after the interventional pain management. They will be
      centrifuged (2000 U/min) at 4C, and stored at 80C. Serum TNFα will be measured with a
      high-sensitivity TNFα Quantikine immunoassay.

      3) Radiological assessment: Magnetic Resonance imaging of the lumbosacral spine will be
      performed for all patients included in the study.

      Magnetic Resonance imaging (MRI):

      The following protocols will be used:

        1. T1- weighted images (axial, sagittal).

        2. T2- weighted images (axial, coronal).

        3. Fluid attenuated inversion recovery (FLAIR) sequence. 4) Interventional pain management:
           Patients will be randomly assigned into one of two groups. In all cases taken to the
           operating room, routine monitoring was conducted. ECG, noninvasive blood pressure and
           peripheral arterial saturation (SpO2) was monitored. After the monitoring, patients will
           be taken the convenient position for the procedure. The C-arm fluoroscopy will be used
           for imaging during process.

      (1) Transforaminal steroid injection group: The selected patients will receive transforaminal
      epidural injection of premixed steroids with local anesthetic in a total volume 2 ml (7 mg
      Betamethasone and 20 mg Lidocaine 2%) (2) radiofrequency on dorsal root ganglion combined
      with transforaminal steroids injection group: The needle puncture site determined by
      fluoroscopy. The Radiofrequency (RF) application was performed to all patients as detailed
      below: following subcutaneous local anesthesic infiltration, Cosman RFG1A Lesion Generator
      (Cosman Medical, Inc., Burlington, Massachusetts, USA) was used for RF thermo-ablation.

      RF cannula (22 g, 10 cm, 5 mm active electrode tip or 5 cm, 2 mm active electrode tip) was
      placed in a determined puncture site before processing and then the electrode was placed into
      the cannula. Electrical stimulation at a frequency of 50 Hz was given for sensory testing
      after 300 to 700 ohms of impedance values were observed.

      Paresthesia was questioned asking patients whether there is any pressure, compression or
      increase in pain where the needle tip was while testing. We accepted that the cannula is in
      the right place when paresthesia occurs below 0.5V. Motor stimulation was given with a
      frequency of 2 Hz. Motor response did not occur above 1.5 V. RF procedure was started after
      our location also confirmed by fluoroscopy. Pulse RF current at 42 °C at 20 ms 2 times per
      second was performed to patients for 360 seconds. The electrode was removed and needle entry
      site was closed with a sterile spunch after procedure completed. Patients were discharged
      within 6 hours .

      Sample size calculation The sample size calculation was done using G*Power version 3.1.9.2
      Software. Effect size f=0.25, α err prob=0.05, Power (1-β err prob)=0.80, Number of groups=2,
      Corr among rep measures=0.17, Noncentrality parameter λ=8.396, Critical F=4.007, Numerator
      df=1, Denominator df=58, Total sample size=60, Actual power= 0.813.
    

Intervention name(s): Radiofrequency pulsed mode on dorsal root ganglion combined with transforaminal steroids injection; Transforaminal injection of Steroids alone
Intervention type(s): Procedure; Drug
Intervention description(s): Radiofrequency pulsed mode on dorsal root ganglion combined with transforaminal steroids injection; Transforaminal injection of Steroids alone
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: To compare the effect of transforaminal injection of Steroids alone versus Radiofrequency pulsed mode on dorsal root ganglion combined with transforaminal steroids injection on TNF-α level in lumbar disc related radicular pain
Masking: Double (Participant, Investigator)
Primary purpose: Treatment