Back/Spine – Disc Pathology – PRP Therapy

Background:

Platelet-Rich Plasma (PRP) has been used for a variety of musculoskeletal disorders including tendinopathies and Osteoarthritis. Few studies exist for PRP therapy in the spine, except for studies involving disc pathology. However, numerous studies exist involving the use of Prolotherapy for spinal disorders. Both Prolotherapy and PRP can be considered within the broad category of Regenerative Injection Treatment (RIT), which are proposed to strengthen or repair injured ligaments, tendons, muscle, cartilage, and bone via injections of proliferative solutions, growth factors, or cells. Provided that double-blind randomized controlled trials have shown both PRP and Prolotherapy to be effective in treating similar regions of the body, it is reasonable to consider that PRP could be comparatively effective as Prolotherapy in treating pain related to the facet joints, capsules, and associated spinal ligaments.

Objective:

We aim to provide an overview of Prolotherapy and PRP applications in the spine and present a 5 patient case series of PRP injections involving the lumbar, thoracic, and cervical spine.

Study design:

This study is a single-center observational case series with 5 patients. Patients were selected based on strict diagnostic criteria and inclusion factors. Each patient received a series of 3 PRP injections into the affected facet joints and surrounding ligaments using fluoroscopic or ultrasound guidance. Relative immobilization with bracing was prescribed for 72 hours following the injections. Follow up examinations ranged from 6-12 months.

Setting:

Procedures were performed in an outpatient setting in Los Angeles, California.

Results:

Case 1: 60% symptom improvement following 2nd injections, 100%improvement & return to sport at 6 months; Case 2: at least 30% symptom improvement following 1st injection, 60% improvement following the 2nd series, &1/10 VAS scale at 9 months; Case 3: at least 40% symptom improvement following 2nd injections, 2/10 VAS scale and improvement in functional status at 12 months; Case 4: 70% symptom improvement & increased functional status following 3rd injections; Case 5: 65-70% symptom improvement and increased functional status at 6-month follow-up. Patients reported reduced fear and anxiety over inciting events, improved sleep, and decreased pain medication use.

Limitations:

The self-reported VAS pain scale and functional scores could be a source of bias and potentially decrease the validity of the results. However, the cost-effectiveness and subjectivity of such measurements make it an easy to use method for measuring therapeutic efficacy through patient satisfaction, regardless of objective measures. The small sample size is also a limitation, and larger patient sizes in future studies are needed to further evaluate the treatment’s effectiveness. In addition, the follow-up time ranged from 6-12 months. To better assess the long term effects of such treatment, patient follow-up at 18 and 24 months would provide better long term data.

Conclusions:

Platelet Rich Plasma injections can potentially represent a viable treatment option for spinal pain related to facet joints, capsules, and spinal ligaments. Further investigation with larger patient numbers and longer follow-up periods are needed.

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Context:

Low back pain (LBP) is a complex and disabling condition, and its treatment becomes a challenge.

Aims:

Our study aimed to assess the clinical outcome of plasma rich in growth factors (PRGF-Endoret) infiltrations (one intradiscal, one intra-articular facet, and one transforaminal epidural injection) under fluoroscopic guidance-control in patients with chronic LBP. PRGF-Endoret which has been shown to be an efficient treatment to reduce joint pain.

Settings and Design:

The study was designed as an observational retrospective pilot study. Eighty-six patients with a history of chronic LBP and degenerative disease of the lumbar spine who met inclusion and exclusion criteria were recruited between December 2010 and January 2012.

Subjects and Methods:

One intradiscal, one intra-articular facet, and one transforaminal epidural injection of PRGF-Endoret under fluoroscopic guidance-control were carried out in 86 patients with chronic LBP in the operating theater setting.

Statistical Analysis Used:

Descriptive statistics were performed using absolute and relative frequency distributions for qualitative variables and mean values and standard deviations for quantitative variables. The nonparametric Friedman statistical test was used to determine the possible differences between baseline and different follow-up time points on pain reduction after treatment.

Results:

Pain assessment was determined using a visual analog scale (VAS) at the first visit before (baseline) and after the procedure at 1, 3, and 6 months. The pain reduction after the PRGF-Endoret injections showed a statistically significant drop from 8.4 ± 1.1 before the treatment to 4 ± 2.6, 1.7 ± 2.3, and 0.8 ± 1.7 at 1, 3, and 6 months after the treatment, respectively, with respect to all the time evaluations (P < 0.0001) except for the pain reduction between the 3 and 6 month whose signification was lower (P < 0.05). The analysis of the VAS over time showed that at the endpoint of the study (6 months), 91% of patients showed an excellent score, 8.1% showed a moderate improvement, and 1.2% were in the inefficient score.

Conclusions:

Fluoroscopy-guided infiltrations of intervertebral discs and facet joints with PRGF in patients with chronic LBP resulted in significant pain reduction assessed by VAS.

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The intervertebral disc is the primary cause if not the contributing factor in the vast majority of cases of back pain. Disc degeneration may start with a circumferential tear of the annulus fibrosus, progressing to a radial tear, herniation, loss of disc height, and resorption. Nucleus pulposus cells retain the notochordal cell markers cytokeratin CK-8, -18, and -19 and Galectin-3 and cluster adjacent to areas of disc disruption, indicating an innate capability for disc regeneration. The low number of cells available for disc regeneration (4,000 nucleus pulposus cells/mm3 and 9,000 annulus fibrosus cells/mm3) makes it difficult if not impossible for larger tears to be repaired. Platelet-rich plasma (PRP) lysate and bone morphogenic proteins (BMPs) have been shown to augment the intervertebral disc repair process in animal models. Platelets have the ability to recognize, adhere to, pull together, and hold disrupted tissues with forces ranging from 29 to 70nN per platelet. Based on these findings, we are conducting a clinical trial of intra-discal PRP injections in humans. Patients and discs are selected based on history and physical examination, magnetic resonance imaging, anesthetic discography, and lack of improvement following physical therapy, epidural and facet injections. At the time of publication, we performed 47 disc injections in 35 patients at one or more levels in the lumbar and thoracic spine with our first cases reaching a 1-year follow-up. We describe 5 case examples typifying the positive response seen in approximately two-thirds of the patients.

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Background

Platelet-rich plasma (PRP therapy) has been found to be effective for a variety of musculoskeletal conditions. The treatment of discogenic pain with PRP is under investigation.

Objective

To assess changes in pain and function in patients with discogenic low back pain after an intradiscal injection of PRP.

Methods

Patients were diagnosed with discogenic low back pain by clinical means, imaging, and exclusion of other structures. Provocation discography was used in a minority of the patients. Patients underwent a single treatment of intradiscal injection of PRP at one or multiple levels.

Main Outcome Measures

Patients were considered a categorical success if they achieved at least a 50% improvement in the visual analog score and 30% decrease in the Oswestry Disability Index at 1, 2, and 6 months post-treatment.

Results

22 patients underwent intradiscal PRP therapy. Nine patients underwent a single level injection, ten at 2 levels, two at 3 levels, and one at 5 levels. Categorical success rates were as follows: 1 month: 3/22 5 14% (95% CI 0% to 28%), 2 months: 7/22 5 32% (95% CI 12% to 51%), 6 months: 9/195 47% (95% CI 25% to 70%).

Conclusion

This trial demonstrates encouraging preliminary 6-month findings, using strict categorical success criteria, for intradiscal PRP as a treatment for presumed discogenic low back pain. Randomized placebo-controlled trials are needed to further evaluate the efficacy of this treatment.

Purpose

The aim of this article is to provide an overview of clinical and translational research on intradiscal platelet-rich plasma (PRP) as a minimally invasive treatment for discogenic low back pain.

Methods

A literature review of in vitro, in vivo, and clinical studies was performed.

Results

It is strong in vitro evidence that supports the use of intradiscal PRP for discogenic low back pain. There are also promising findings in select preclinical animal studies. A clinical study of 29 participants who underwent intradiscal PRP injections for discogenic low back pain found statistically and clinically significant improvements in pain and function through two years of follow-up.

Conclusions

Intradiscal PRP therapy is a safe and possibly effective treatment for discogenic low back pain. Future studies are warranted to determine the best candidates for this treatment, what the optimal injectate is, and what relationships exist between patient-reported outcomes and radiological findings.

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Background:

Stromal vascular fraction (SVF) can easily be obtained from a mini-lipoaspirate procedure of fat tissue and platelet-rich plasma (PRP) can be obtained from peripheral blood. The SVF contains a mixture of cells including ADSCs and growth factors and has been depleted of the adipocyte (fat cell) population. We evaluated the safety and efficacy of administering SVF and PRP intradiscal into patients with degenerative disc disease.

Methods:

A total of 15 patients underwent a local tumescent liposuction procedure to remove approximately 60 ml of fat tissue. The fat was separated to isolate the SVF and the cells were delivered into the disc nucleus of patients with degenerative disc disease. The subjects were then monitored for adverse events, range of motion, visual analog scale (VAS), present pain intensity (PPI), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI), Dallas Pain Questionnaire, and Short Form (SF)-12 scores over a period of 6 months. Safety events were followed for 12 months.

Results:

No severe adverse events (SAEs) were reported during a 12 month follow-up period with no incidences of infection. Patients demonstrated statistically significant improvements in several parameters including flexion, pain ratings, VAS, PPI, and short-form questionnaires. In addition, both ODI and BDI data were trending positive and a majority of patients reported improvements in their Dallas Pain Questionnaire scores.

Conclusions:

Overall, patients were pleased with the treatment results. More importantly, the procedure demonstrated a strong safety profile with no severe adverse events or complications linked to the therapy. Trial registration NCT02097862. Name of the registry: www.clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02097862?term=bioheart&rank=6. Date of registration: March 25, 2014; Date of enrollment: March 2014

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Objective:

To determine whether single injections of autologous platelet-rich plasma (PRP) into symptomatic degenerative intervertebral disks will improve participant-reported pain and function.

Design:

A prospective, double-blind, randomized controlled study.

Setting:

Outpatient physiatric spine practice.

Participants:

Adults with chronic (!6 months), moderate-to-severe lumbar discogenic pain that was unresponsive to conservative treatment.

Methods:

Participants were randomized to receive intradiscal PRP or contrast agent after provocative discography. Data on pain, physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year. Participants in the control group who did not improve at 8 weeks were offered the option to receive PRP and subsequently followed.

Main Outcome Measures:

Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function domains of the 36-item Short-Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire were used.

Results:

Forty-seven participants (29 in the treatment group, 18 in the control group) were analyzed by an independent observer with a 92% follow-up rate. Over 8 weeks of follow-up, there were statistically significant improvements in participants who received intradiscal PRP therapy with regards to pain (NRS Best Pain) (P 1⁄4 .02), function (FRI) (P 1⁄4 .03), and patient satisfaction (NASS Outcome Questionnaire) (P 1⁄4 .01) compared with controls. No adverse events of disk space infection, neurologic injury, or progressive herniation were reported following the injection of PRP.

Conclusion:

Participants who received intradiscal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI scores through at least 1 year of follow-up. Although these results are promising, further studies are needed to define the subset of participants most likely to respond to biologic intradiscal treatment and the ideal cellular characteristics of the intradiscal PRP injectate.

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Purpose

Intervertebral disc degeneration is a common disease that usually starts from the third decade of life and it represents a significant cause of socio-economic problems. The accepted surgical treatment for disc degeneration is disc removal and vertebral fusion or, in selected cases, intervertebral disc arthroplasty. Several studies have demonstrated the ability of platelet-rich plasma (PRP therapy) to stimulate cell proliferation and extracellular matrix regeneration. However, literature results are still limited and more studies are required to clarify the role of PRP in the prevention or the treatment of degenerative disc disease. The aim of this review is to summarize and critically analyze the current preclinical evidence about the use of PRP in intervertebral disc degeneration.

Methods

A literature search was performed through various combinations of the following keywords: Intervertebral Disc Degeneration, Platelet Rich Plasma, PRP, Intervertebral disc regeneration. Papers included in our review cover the period between 2006 and 2014. The PRISMA 2009 checklist was followed.

Results

At the end of the review process, 12 articles were included in our final manuscript, including 6 ‘‘in vitro’’ and 6 ‘‘in vivo’’ studies. All the included studies lead to positive preclinical results. No standardization of methodological analysis was observed.

Conclusion

It is not possible to draw definitive evidence about the use of PRP in IVD regeneration. We advise a proper standardization of the methodological analysis in order to compare the available data and achieve definitive results. This should be the cornerstone for future clinical applications.

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Intervertebral disc degeneration is a chronic disease That causes significant disability and dependence and exerts a high cost on society. It is the MOST common cause of back pain and may involve any segment of the spine, the lumbar being the Most Frequently AFFECTED area. It is one of the MOST frequent reasons for consultation in the overall population, second only to headache, affecting 80-85% of people throughout Life. Current therapeutic strategies are
primary conservative, treats including physical therapy and anti-inflammatory medication. Surgical techniques are Intended only to stabilize the spine and/or decompress the spinal canal or foraminal, searching for relief of symptoms; however, do not address the cause of the degeneration and even accelerate the degeneration of adjacent segments. Understanding the biology of platelet-rich plasma (PRP therapy) and Its effect on chondral repair has led to the use of PRP as a promising therapeutic strategy for biological Enhance the regenerative process and healing of the intervertebral disc. Very few studies Have Been Conducted in vitro and there are even fewer clinical studies PRP Which link With the management of degenerative disc disease. At present, there is no document linking PRP used in injection into the epidural space as a method of intervertebral disc regeneration in cases of disc disease. This is a preliminary study of pain management in patients with degenerative disc disease and axial pain, by using PRP injected into the epidural space, lumbar or cervical.

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Introduction:

Lumbar radiculopathy is a major health problem often treated by surgery or guided lumbar epidural steroids for pain relief. We have used Platelet Rich Plasma (PRP therapy) a novel therapeutic tool of autologous nature that has emerged strongly in recent years to treat patients of the prolapsed intervertebral disc.

Aim:

To evaluate the efficacy of PRP via the interlaminar epidural route in the treatment of pain in patients with prolapsed intervertebral disc.

Materials and Methods:

Ten patients were injected with five ml of autologous platelet-rich plasma under fluoroscopic guidance via interlaminar lumbar epidural injection into the area of the affected nerve root. They were followed using the VAS (Visual Analogue Scale), SLRT (Straight Leg Raising Test), and MODQ (Modified Oswestry Disability Questionnaire) for clinical improvement.

Results:

Patients who had received epidural injections of autologous PRP showed improvements in their scores of evaluation tools. Improvement was sustained during the 3 month study period and was not associated with any complications.

Conclusion:

Autologous PRP can be considered as a good alternative to epidural steroids and surgery in the management of patients with chronic prolapsed intervertebral disc.

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The goal of this case review is to evaluate functional and structural changes with the use of intradiscal PRP therapy in patients with lumbar discogenic pain. The secondary outcomes include improvement in pain, medication use, hospitalization, and surgery. Low back pain affects a large portion of the population causing a major social and economic effect. Current interventional treatments remain inadequate and transient targeting the symptoms without addressing the underlying cause. Platelet-rich plasma (PRP) has been used clinically in various settings for its healing properties attributed to growth factors. A total of 6 patients with chronic discogenic low back and leg pain who tried and failed conservative treatments were administered a single injection of 2-mm autologous PRP into the nucleus pulposus after careful study of the disk anatomy via discography and computed tomography scan. The patients were

followed up at 2, 4, 8, 12, 16, 20, and 24 weeks; postinjection and primary and secondary outcomes were recorded. The verbal pain scale score for the pain of all patients decreased by more than 50% and their function increased for a period of 6 months and beyond. Postprocedure magnetic resonance imaging documented positive structural changes in a small percentage of patients. None of the patients presented to the hospital or received surgery after this treatment. Although our preliminary results have been promising, well-designed randomized controlled trials are warranted to understand the full breadth of the efficacy, risks, and complications from the use of PRP in the disk.

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Human intervertebral disc (IVD) degeneration is often initiated from the human nucleus pulposus (hNP) with aging leading to IVD destruction and extracellular matrix (ECM) depletion. Previously, we have successfully employed transforming growth factor-b1 (TGF-b1) to promote chondrogenesis of mesenchymal progenitor cells (MPCs) and immortalized human mesenchymal stem cells. In this study, we examine the role of TGF-b1 in platelet-rich plasma (PRP therapy) on disc regeneration, including proliferation, redifferentiation, and the reconstitution of tissue-engineered NP. hNP cells were isolated from volunteers of different ages and cultured in the presence of PRP. We found that the most effective concentration for hNP proliferation was 1 ng/ml TGF-b1 in PRP, which was further applied in the following experiments. hNP cell proliferation in all age groups was increased time-dependently by PRP and cell morphologies showed aggregation. The mRNA of Sox9, type II collagen, and aggrecan were all significantly upregulated by PRP through RT-PCR. Glycosaminoglycan (GAG) accumulation reached the highest value at day 7 and continued to day 9 culture. PRP promoted NP regeneration via the Smad pathway was also determined and highly activated p-Smad2/3 at 30 min and continuously sustained to 120 min. Immunostaining of type II collagen indicates that PRP participates in chondrogenesis of tissue-engineered NP with collagen scaffolds. We concluded that growth factors in PRP can effectively react as a growth factor cocktail to induce hNP proliferation and differentiation, and also promote tissue-engineered NP formation. These findings are the first to demonstrate that PRP might be a therapeutic candidate for the prevention of disc degeneration. J. Cell. Physiol. 209: 744–754, 2006.

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Back pain is the second leading cause of disability among American adults and is currently treated either with conservative therapy or interventional pain procedures. However, the question that remains is whether we, as physicians, have adequate therapeutic options to offer to the patients who suffer from chronic low back pain but fail both conservative therapy and interventional pain procedures before they consider surgical options such as discectomy, disc arthroplasty, or spinal fusion. The purpose of this article is to review the potential novel therapies that are on the horizon for the treatment of chronic low back pain. We discuss medications that are currently in use through different phases of clinical trials (I–III) for the treatment of low back pain. In this review, we discuss revisiting the concept of chemonucleolysis using chymopapain, as the first drug in an intradiscal injection to reduce herniated disc size, and newer intradiscal therapies, including collagenase, chondroitinase, matrix metalloproteinases, and ethanol gel. We also review an intravenous glial cell-derived
a neurotrophic growth factor called artemin, which may repair sensory nerves compressed by herniated discs. Another new drug in development for low back pain without radiculopathy is a subcutaneous monoclonal antibody acting as a nerve growth factor called tanezumab. Finally, we discuss how platelet-rich plasma and stem cells are being studied for the treatment of low back pain. We believe that with these new therapeutic options, we can bridge the current gap between conservative/interventional procedures and surgeries in patients with chronic back pain.

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