INTRODUCTION

Low back pain is one of the most difficult conditions to manage for doctors, patients, and policymakers. Not only does it limit physical activity, life quality is also greatly reduced alongside additional social and economic burden. The point prevalence of low back pain is 12%, with its one-year prevalence being 38% and the lifetime prevalence being approximately 40%¹. Aging population leads to the rising number of individuals affected by low back pain. Lumbar disc herniation has been identified as the common etiology of low back pain². The treatments for lumbar disc herniation vary from conservative to surgical management, which include analgesics, traction, physical therapy, manipulation, and psychotherapy. However, not all patients are able to be relieved from pain through these treatments.

For over 30 years, epidural steroid injection has been widely used as a treatment for lumbar disc herniation^{3, 4}, with its effectiveness proven by multiple research^5–7. It works in anti-inflammation, pain relief, and functional improvement. There are three routes for steroid injection: interlaminar, transforaminal, and caudal routes. The transforaminal route fared better than the other two because it could reach the targeted sites, namely, spinal nerve, anterior epidural space, and the dorsal root ganglion, to counteract the inflammation secondary to compression.⁵However, there are still concerns about the safety of epidural steroid injection. Based on literature, several complications related to epidural steroid injection have been pointed out, including neurotoxicity, pharmacologic effect of steroid (hypercorticism, adrenal suppression, and hyperglycemia), and neurologic injury^6,7. Besides, the contraindications of steroid use (allergy, diabetes, severe osteoporosis, pregnancy, severe hypertension, infection, etc.) limit the usage of epidural steroid injection.

Autologous platelet-rich plasma is a blood-derived product obtained through centrifugation, when platelet concentrations are three times higher than baseline in plasma. This procedure allows the degradation of platelet α-granules and the release of several important growth factors such as platelet-derived growth factor ([PDGF-αα], [PDGF-αβ], [PDGF] -ββ]), endothelial growth factor (VEGF), two transforming growth factor-β ([TGF-β1] [TGF-β2]) and epithelial growth factor (EGF). Mostly PRP has been used for chronic tendinopathy and enthesopathy, including knee osteoarthritis. It has become an important tool for use of pain physician because of low cost, ease of use and its apparent safety.^8,9

Platelet-rich plasma (PRP), a biological product from the centrifugation of autologous blood with a high number of platelets in a small volume of plasma, has a positive effect on pain relief in some musculoskeletal diseases, especially osteoarthritis, tendinosis, and ligament tears¹⁰. PRP contains high concentration of growth factors (GFs) and cytokines that play important roles in anti-inflammatory, antiapoptotic, and proliferative effects on the neurons and fibroblasts¹¹. Although the role of PRP in pain relief looks promising, the effect of transforaminal PRP injection in lumbar disc herniation with radicular pain remains unclear.

AIMS AND OBJECTIVES

AIM :

·         To compare the efficacy and safety of autologous platelet rich plasma injection versus Triamcinolone in lumbar disc herniation with radicular pain through C-arm guided technique.

Primary Objective :

–     To compare pain relief with PRP Vs Triamcinolone in transforminal epidural for radicular pain due to lumbar disc herniation via VAS.

Secondary objective:

–     To compare patients satisfaction with PRP vsTriamcinolone

–     To compare safety and side effects of PRP vsTriamcinolone

MATERIAL AND METHODS

Study setting:

The study will be conducted in Pain OT, Department of Anesthesiology, King George’s Medical University, Lucknow after written informed consent will be obtained from either of the patients/Guardian

Study duration :One year 

Study design:

Prospective Randomized control study

Sample size:

60 cases(30 in each group)

Inclusion Criteria:

·         Patients giving written consent will be taken

·         Patient in the age group of 20 to 60 years.

·         ASA grade I & II

·         Low back pain more than 3 months and unilateral lower limb with radicular pain

·         Posterolateral lumbar disc herniation of L4/L5 or L5/S1 segment on CT and corresponding clinical symptoms and signs

·         Pain level on VAS â‰¥5

·         No symptoms of severe nerve damage include motor paralysis, muscle atrophy and cauda equine syndrome

·         No history of spinal surgery

Exclusion Criteria:

·         Patients not giving informed consent

·         ASA grade III to IV

·         Infection

·         Prior epidural injection in the past 3 months, such as nerve root injection and caudal injection

·         Spinal tumors or tuberculosis

·         Multi-segmental lumbar disc herniation, spinal deformity, or spinal stenosis

·         Allergic to the drug used in this study

·         Symptoms of severe nerve damage including motor paralysis, muscle atrophy, and caudaequina syndrome.

Ethical approval:

·         It will be taken from the Institutional Ethics Committee of the university.  

Methodology:

•      Patients will be divided randomly in two groups:

–     Group A: Patients administered transforaminal epidural injection of platelet rich plasma (4ml).

–     Group B: Patients administered transforaminal epidural injection of steroid (2ml triamcelone+ 2ml 0.9% normal saline)

Sample size

On the basis of previous study, the changes in the mean d OSS scores between the PRP (16.2 ) and corticosteroid groups (25.0) at 6-month follow-up was 8.8 and the population variance (σ2) was 10.2 (Thepsoparn et al., 2021).¹¹The sample size (n) = 2 (Zα/₂ + Z _[1-β])² × σ²/( μ1−μ2)²,assuming 0.05 level significance (Z_α/2 =1.96), and 90% power (Z _[1-β])=1.28) was 28.20 in each group. Considering any dropouts, we had enrolled 30 patients in each group. ¹¹

2 (Zα/₂ + Z _[1-β])² × σ²

n=

      (μ1−μ2)²

2 (1.96 + 1.28)² × 10.2²

n=

    (25-16.2)²

n=28.20

Procedure

The patients enrolled to this study underwent physical examination,neurological examination, and laboratory tests. The operation will be  performed at the Pain OT, Department of Anaesthesiology,KGMU, Lucknow

The procedure of PRP preparation will be follows: 18 ml blood sample will be drawn from the anterior elbow vein and mixed with 2 ml of 3.8% (w/v) sodium citrate (total 20 ml). The blood sample will be centrifuged at 1600 rpm for 10 min at room temperature (23 Â°C) under aseptic condition to divide the sample into 3 layers. The lower layers, composed of red blood cells, will be subsequently removed. The remaining sample will be transferred into a new centrifuge tube and was centrifuged again at 3200 rpm for 10 min at room temperature. 4 ml was collected from the lower part which contains PRP.

Technique of transforaminal PRP injection: the patient lied prone, under local anesthesia. To determine the point for injection: 3–5 cm from midline, depending on the side with corresponding symptoms, check the right segment below the C-arm. Align the C-arm head in the diagonal direction until the superior articular surface of the lowervertebrae is in the middle of the disc space. Insert the 22G Spine needle in the direction of the lamp head, gently until it passes the outer edge of the superior joint. Adjust the lamp head in the front and back direction, determine that the needle tip is on the inter-peduncle seam. Align the lamp head in the lateral direction; locate the needle tip at the lower back of the conjugate hole. Gently withdraw the syringe to check for blood orcerebrospinal fluid. Inject 1 ml of Omnipaque 300 contrast agent, check the C-arm to see if the drug spreads along the path of the nerve roots into the epidural area. Inject 4 ml Platelet Rich Plasma. Withdraw the needle and apply a sterile bandage at the injection site. Check vital signs after the procedure. Same procedure will be done for group B patients

Patients will be evaluated after 1 h of procedure and discharged with advice to avoid too much bending, lifting heavy weight or walking long distances and asked to follow-up at 1 week, 2 weeks, 1 month and 3 months. VAS score, and likert scale will be recorded at all times. Neurological check-up of lower limb included motor examination in form tone, muscle strength, reflexes and sensory examination as well as side effects of procedure will be evaluated.

Measurement of outcome

Patients’ characteristics comprise of gender, age and baseline data upon admission. Baseline data will be collected including visual analogue scale (VAS), and Likert scale. Randomization will be done as computer generated random number table.

Firstly, the visual analogue scale (VAS) will be a method to evaluate the degree of pain. A 10 cm line as an indicator presented one end meaning no pain, while the other end meaning the most severe pain. The patient will be asked to indicate the point on the line which could represent patient’s pain level.

VAS: before injection and after injection for 1 week, 2 weeks, 4 weeks and 12 weeks. To define as effective in pain relief, pain level post-op had to be smaller than pre-op at least 2.5 points and had to decrease ≥50% compared to pre-op, according to VAS.

Likert scale assumes that the strength/intensity of an attitude is linear, i.e. on a continuum from strongly agree to strongly disagree, and makes the assumption that attitudes can be measured.

Statistical analysis:

Data will be entered in Microsoft excel and analyzed using statistical software SPSS version25( Chicago, IL,  USA). Student’s t test will be used to analyze parametric data, while the Mann-Whitney U test was applied to non-parametric data and Fisher’s test to categorical data. P values < 0.05 will be considered statistically significant.

REVIEW OF LITERATURE

Bodoret al. [2014] studied 35 patients who were given 47 disc injections of PRP in the lumbar and thoracic spine (28). Two-thirds of the patients showed positive outcomes. The authors also presented a detailed case series of five patients with discogenic back pain treated with PRP injections. The follow-up period ranged from ten days to 10 months, in which patients exhibited substantial improvements in pain that enabled them to return to normal physical activities. Despite two patients having vasovagal episodes, there were no complications or side effects related to this treatment.¹²

In 2016, Levi et al.¹³ published data from a prospective clinical trial on 22 patients examining the effect of intradiscal PRP injection on discogenic back pain (35). No complications or serious side effects were reported. Back pain was measured using a visual analogue scale (VAS) and Oswestry Disability Index (ODI). After a 6-month follow-up period, 47% of patients reported at least a 50% improvement in pain and a 30% improvement in their ODI score. The authors speculate that the time frame required for the treatment to take effect, possible adverse effects from the anesthetics and antibiotics used during the procedure, and the PRP preparation method used, account for the lack of a significant positive outcome in this study. In another study by Navani and Hames [2015],¹⁴ six patients were given a single injection of 1.5–3 mL of autologous PRP (36). At a 24-week follow-up, patients reported a 50% decrease in pain according to the verbal pain scale (VPS), with no adverse effects reported.

In 2016, Hussein and Hussein performed a clinical trial on 104 patients with chronic low back pain. Unlike the studies mentioned earlier in this section, platelet leucocyte-rich plasma (PLRP) was used instead of PRP, owing to the phagocytic nature of leucocytes. Injections were carried out weekly for 6 weeks. The method was proven to be a safe and effective method for relieving chronic low back pain, with a success rate of 71.2% reported by the authors. No adverse effects or complications were reported other than short-term pain at the injection site.¹⁵

The first double-blind randomized controlled trial (RCT) of intradiscal PRP therapy was performed by Tuakli-Wosornuet al. in 2016 on 47 participants with chronic lumbar discogenic pain. Participants with a history of chronic axial low back pain were recruited and were randomly allocated to treatment or control groups at a 2:1 ratio, respectively. At an 8-week follow-up, outcomes were measured by Functional Rating Index (FRI), Numeric Rating Scale (NRS)-best pain, the Short Form (SF)-36, and modified North American Spine Society (NASS) satisfaction scores. The study found statistically significant improvements in the treatment group, and the effects of PRP were sustained for a period of at least 1 year according to FRI scores. No complications were reported.¹⁶

In a pilot study performed on ten patients in 2016 by Bhatia and Chopra, PRP injections were shown to improve pain. Patients suffering from chronic prolapsed intervertebral discs were given single 5 mL injections of autologous PRP and were followed up after 3 months. Improvement in pain was evaluated using VAS, the Modified Oswestry Disability Questionnaire (MODQ) index and Straight Leg Raising Test (SLRT). All patients had a gradual improvement in symptoms that persisted for at least three months without any complications.¹⁷

In 2017, Akedaet al. conducted a clinical study investigating the safety and feasibility of autologous PRP releasate injections for discogenic low back pain. PRP releasate is a form of bioactive soluble factors isolated from activated PRP that can stimulate tissue repair. The authors implicated that the platelets were isolated by the buffy coat (BC) method and therefore contained lower concentrations of pro-inflammatory cytokines; hence, the sample was considered as “pure PRP”. This prospective, preliminary clinical study was carried out in 14 patients with lumbar discogenic low back pain for a period of 10 months. Seventy-one percent of patients showed a 50% reduction in pain as measured by VAS scores; however, low back pain returned in two patients. In contrast to the VAS scores, physical disability scores [Roland-Morris Disability Questionnaire (RDQ)] were significantly reduced in 79% of patients. Apart from temporary leg numbness in two patients, no other notable adverse events were reported. In summary, this study proved the safety, feasibility and efficacy of PRP in the treatment of lumbar discogenic back pain.¹⁸

A single case report by Lutz [2017] reported on the effectiveness of intradiscal PRP injection for improving low back pain and function. The patient was diagnosed with a degenerated disc and had received an ineffective caudal epidural steroid injection and physical therapy. The patient was given a single PRP injection and showed considerable improvement in pain and motion after 6 weeks. At a 1-year follow-up, there was remarkable improvement in low back pain and the patient was able to return to athletic activities.¹⁹

The clinical studies discussed so far in this review demonstrate the efficacy of autologous PRP when applied alone in the treatment of chronic back pain. Therefore, a report which shows the effect of PRP injection together with another agent [stromal vascular fraction (SVF)] is particularly interesting. Comellaet al. investigated the safety and efficacy of PRP in combination with SVF delivered into the disc nucleus of patients with degenerative disc disease. SVF is a mixture of adipose-derived stem cells (ADSCs) and growth factors. The study proved to be safe and successful with significant improvements in flexion, VAS, and pain scores according to the Present Pain Intensity (PPI) scale, SF-12 and Dallas Pain Questionnaires (DPQ). The majority of patients reported remarkable reductions in pain compared to baseline over a period of 6 months post-injection. The only side effects reported were soreness in the abdomen from liposuction (for SVF) and soreness in the back from the PRP injection, both of which resolved within 1 week.²⁰

Mohammed S  et al (2018) conducted a study that Autologous platelet-rich plasma (PRP) injections have been investigated in recent years as an emerging therapy for various musculoskeletal conditions, including lumbar degenerative disc disease. Although PRP has received increasing attention from medical science experts, comprehensive clinical reports of its efficacy are limited to those treating knee osteoarthritis and epicondylitis. Use of PRP is gaining popularity in the area of degenerative disc disease, but there is a clear need for reliable clinical evidence of its applications and effectiveness. In this article, we review the current literature on PRP therapy and its potential use in the treatment of chronic discogenic low back pain, with a focus on evidence from clinical trials.²¹

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