Skip to main content
NCBI home page
Interventional Pain Medicine logoLink to Interventional Pain Medicine
. 2025 May 30;4(2):100598. doi: 10.1016/j.inpm.2025.100598

Effectiveness of epidural amniotic fluid injection for low back pain

Glenn R Buttermann a,⁎, Matthew Thorson b, Louis C Saeger c
PMCID: PMC12166700  PMID: 40519791

Abstract

Background

Epidural corticosteroid injections have long been used to treat pain and inflammation associated with low back conditions including symptoms due to lumbar herniated disc, HNP; spinal stenosis, SS; and degenerative disc disease, DDD. Amniotic fluid, AF, is rich in the proteins and factors that are believed to contribute to healing by minimizing inflammation. AF injections in non-spinal conditions have been shown to be safe and avoid adverse effects related to steroids.

Objectives

To investigate the safety and efficacy of a single amniotic fluid injection into the lumbar epidural space for the treatment of low back pain. Specifically, this pilot study was to define indications for future large scale comparative studies.

Methods

This IRB approved prospective clinical study of 3 cohorts included 20 patients each with HNP, SS, and DDD with a 1-year follow-up. Patients were enrolled who had LBP ± leg symptoms for >2 months, with clinical and MRI findings for HNP, SS, or DDD. Inclusion criteria necessitated that study patients had not responded to medications, physical therapy, and/or chiropractic. After obtaining consent, 20 patients in each diagnostic group (HNP, SS, and DDD) had 2 cc′s transforaminal epidural AF injected at the primary symptomatic level using fluoroscopy. Pre- and post-procedure outcomes measurements were obtained at follow-up periods of 2–3 weeks, 6–8 weeks, 3–4 months, 6–8 months and 1 year. Outcome measures were Visual Analog Scale (VAS) for back and leg pain, Oswestry Disability Scale (ODI), Patient-Reported Outcomes Measurement Information System (PROMIS) scores, and pain medication usage. Using the VAS and ODI measurements, Minimal Clinical Important Difference (MCID) and Success (50 % improvement) rates were derived.

Results

The average age (years) of HNP, stenosis, and DDD patients was 46, 60, and 46 respectively. There were no complications or other adverse effects. HNP patients had the greatest reduction in symptoms with average LBP VAS improvement from 6.3 to 2.9, leg VAS from 5.9 to 2.2, ODI from 37 to 19, and PROMIS Physical component 13.1 to 14.7. SS patients had LBP VAS improvement from 6.8 to 5.3, leg VAS from 5.8 to 3.1, ODI from 46 to 33 and PROMIS Physical component 10.9 to 13.0. DDD patients had LBP VAS from 7.0 to 4.8, leg VAS from 3.9 to 2.7, ODI from 41 to 37 and PROMIS Physical component 12.0 to 13.1. HNP patients had a significant reduction in pain medication use. Over the one year follow-up, the HNP group had the greatest rate of attaining MCID (65 %–79 %) and Success (47 %–60 %). SS had a similar rate of Success for leg pain. ODI MCDI and Success rates were significantly greater for HNP vs the other 2 groups. Overall, 15 % of patients had additional injections and 20 % went on to surgery.

Conclusions

AF epidural injections are most effective for patients with lumbar HNP and moderately effective for those with SS. AF injections for DDD patients gave inconsistent results. Future prospective studies of AF vs steroid injections are warranted for HNP and stenosis patients, particularly in patients with known adverse reactions to steroids.

Keywords: Amniotic fluid, Degenerative disc disease, Disc herniation, Epidural, Outcomes, Spinal stenosis

1. Introduction

Low back pain, LBP, is typically self-limiting, but in some cases may be prolonged. Patients with LBP, with or without radicular pain, are usually first managed conservatively with activity modification, oral medications, physical therapy, chiropractic manipulation, and/or exercise [[1], [2], [3]]. If these efforts do not produce sufficient pain relief, epidural injections of corticosteroid with anesthetic is often performed. The goal of the epidural steroid injections, ESI, is pain reduction, reduced nerve root inflammation, increased function, and in many cases to allow for more optimal physical therapy/rehabilitation.

Aside from muscle strains, axial LBP from degenerative causes, may be broadly categorized into three diagnostic categories, lumbar herniated nucleus pulposus (HNP), degenerative disc disease (DDD), and spinal stenosis (SS). Often patients may present with a combination of the three but usually one of the diagnoses is primary. As part of a conservative management strategy, ESI have long been used to treat pain related to inflammation associated with lumbar HNP, DDD and SS [[4], [5], [6], [7]]. Additionally, successful ESI may reduce surgery rates [8,9]. The therapeutic intention of the injection is to achieve anti-inflammatory activity that decreases back and leg pain symptoms in patients to varying degrees in each of these three groups. It is believed that corticosteroids produce chemical stabilization of the local environment, as well as decreasing cell-mediated inflammatory and immunologic responses [10,11].

Although ESI is often effective in reducing symptoms. Corticosteroids may have deleterious side effects relating to suppression of the hypothalamic-pituitary axis, producing iatrogenic Cushing Syndrome symptoms, hyperglycemia in diabetics, cataracts, osteonecrosis, and risk of subsequent infections [[12], [13], [14]]. The potential adverse effects of steroids limit the total dose of corticosteroid that can be injected. Additionally, patients who fail steroid injections and subsequently undergo surgery, relative to those who do not have steroids, may have an increased risk of spinal infection [15].

As a potential alternative anti-inflammatory agent to steroid, amniotic fluid (AF) contains multiple factors that may serve to ameliorate the detrimental effects of osteoarthritis, DDD, and other musculoskeletal conditions [[16], [17], [18], [19], [20], [21]]. These studies as well as others have demonstrated the safety of AF and other placental derived tissues [[22], [23], [24], [25], [26]]. Human AF is obtained sterilely from women at the time of Caesarean section. At term, AF is composed of not only fetal urine with fetal alimentary and pulmonary tract secretions, but also placental derived proteins [27]. Anti-inflammatory components include inhibitors of matrix-metalloproteinases and anti-inflammatory cytokines (interleukins 4 & 10), but also pro-inflammatory cytokines, growth factors; and it has low immunogenicity [[28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40]]. The anti-inflammatory component of human AF suggests that this treatment may be beneficial for the treatment of radicular pain in the conservative management of pain related to symptoms of HNP, stenosis, and DDD (particularly those with associated with inflammatory end-plate changes).

Prior to initiation of the current study, the investigators had a cumulative experience of 52 epidural AF injections with generally gratifying results. Our uncontrolled anecdotal experience suggested that HNP and DDD patients had longer lasting pain improvement than stenosis patients, although only a few patients fit the stenosis category. Our results were encouraging enough to warrant this prospective study to identify which subgroup of low back pain patients may best be treated with epidural AF injections. We hypothesized that patients with a condition related to greater inflammation would have the greatest improvement in pain. That is, the reduction in pain severity is anticipated to be greatest for disc herniation patients, and less in stenosis and DDD patients.

The objective of this study was to prospectively evaluate the safety and effectiveness in symptom reduction of a single transforaminal epidural AF injection at a level of symptomatic HNP, DDD, or SS over a one-year period. Periodic assessments during the one-year follow-up identified which of these 3 diagnostic groups had the greatest response in pain and disability improvement, and which group(s) maybe be best suited for a future comparative trial of epidural AF against epidural steroid or placebo injection.

2. Methods

2.1. Study IRB description

The present prospective study, approved by the institutional review board (Sterling Institutional Review Board, Atlanta, Georgia, USA), relates to outcomes for AF epidural injection in 3 diagnostic cohorts (n = 20 each). Entry criteria were minimum age of 18 years; low back ± radicular pain >2 months but <8 months; evidence of lumbar SS, HNP, or DDD on MRI; clinical examination findings consistent with MRI findings; inadequate response to conservative care including medication, physical therapy, and chiropractic. Exclusion criteria were active infection, prior lumbar surgery at any level, systemic steroids for another medical condition, pregnancy or breastfeeding, systemic malignancy, known allergy to iodinated contrast, anesthetic, or amniotic products, history of solid organ or hematologic transplantation, autoimmune disorder, current therapy with any immunosuppressive medication, chronic high–dose opioid therapy, severe uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease, inability to consent to procedure due to cognitive issues or language barrier, inflammatory arthritis, intradural disc herniation, or coagulopathy.

Placental tissues, including AF, amniotic membrane and chorion were regulated as human cell and tissue products (HCTP) by the FDA (at the time of the study). This regulation allows clinicians to use the allograft materials for human injections. AF is obtained from carefully screened healthy mothers at the time of scheduled cesarean section. The mothers consented to donate tissues which would otherwise have been discarded. The sterilely aspirated AF is concentrated and then stored with a DMSO free cryoprotectant at −80 °C.

2.2. Procedures

Patients in each arm of the study underwent a transforaminal epidural injection (following fluoroscopic confirmation of appropriate perineural and epidural flow of contrast) of 1 mL preservative-free lidocaine 4 % and two 1-ml dose of acellular AF (2 ml total, Vivex Biologics Inc. Miami, FL, USA). All injections were performed by study investigators (MT, LS), who are board certified in Anesthesiology, with a certificate of additional qualification in pain management, and fellowship-trained in interventional pain management. All injections were performed under fluoroscopic guidance, with contrast control, in accordance with the procedure guidelines (2nd Edition) of the International Spine Intervention Society. Before the procedure, the patients were screened for anticoagulant use.

2.3. Patient reported outcomes

Patients completed prospective baseline self-reported outcomes measures, PROMs, of pain and function; Visual Analog Scale (VAS) for back and leg pain, Pain Drawing, Oswestry Disability Scale (ODI) scores. In addition to these legacy PROMs, the Patient-Reported Outcomes Measurement Information System (PROMIS) a non-disease specific measure, from which Global Health scores were derived, was also used [41,42]. After the epidural injection of AF, patients subsequent completed pain and function outcomes measurements at approximately 2 and 6 weeks, at 3–4 months, 6–8 months, and at 12–14 months post-treatment. Pain medication use was also documented. Outcomes data were tabulated in a blinded fashion to the treating investigators. For patients with missing values due to change in treatment, data were imputed by the Last Observation Carried Forward (LOCF) method, provided the patients had completed at least 2 follow-up evaluations (which they all did). Potential complications were tracked by the investigators as well. Confounding factors were also tracked and included patients with multi-level conditions, new injuries, facet joint pain, and variable opioid tolerance.

2.4. Success of AF injection

Using the VAS and ODI measurements, Minimal Clinical Important Difference (MCID) and Success rates were determined at 3–4 months, 6–8 months and at 10–14 months. Specifically, MCID was a decrease of 2 for back and leg VAS pain scores and an improvement of 30 % in ODI score, and “Success” was a decrease of 50 % for both VAS and ODI scores [43,44]. Additionally, the rate of patient's own general perception of AF injection “success”, and “willingness to repeat the AF injection” were obtained.

2.5. Statistical analysis

Statistical comparisons were made within each group using a two-tailed t-test for all the continuous outcome scales at each time period relative to the pre-injection values. ANOVA was used for the comparison between the 3 groups at each follow-up visit, as well as the overall comparison from pre-op to each follow-up visit. Assessment of attaining MCID, Success, would the subject repeat the injection, and recommending treatment to others were analyzed using Chi-Square test. The differences in pain medication over time within a group was analyzed with McNemar's Exact test. Comparing pain medication use between groups at each time period was made with Fisher's exact test. For patients who failed and progressed to surgery, the Last Observation Carried Forward (LOCF) method was used for all analyses. Probability values of <0.05 were considered statistically significant.

3. Results

The demographics of the patient cohorts varied including average age, percentage of females, percentage of smokers, and those with other levels of disc degeneration, neurological deficits, and workability (Table 1). The SS group was significantly older than HNP and DDD (p < 0.002). The duration of symptoms varied with the HNP patients having significantly shorter duration than the DDD patients (p = 0.016). The most common levels injected were L4-5 and L5-S1. Many patients had also had an epidural steroid injection prior to the AF injection. No patients were lost to follow-up.

Table 1.

Demographics.

HNP SS DDD
Age, mean ± SD 45.7 ± 14.0 59.8 ± 10.0 46.2 ± 12.0
Duration of symptoms (months) mean ± SD 8.4 ± 10.7 47.0 ± 81.3 72.1 ± 106.4
% Female 35 40 55
% Smokers 15 25 20
% Prior Epidural Sterioid Injection 40 65 55
% With Other Levels of Disc Degeneration
 55 90 70
% Pre-injection leg weakness 25 40 0
% Post-injection leg weakness 0 0 0
% Pre-injection leg numbness 45 25 5
% Post-injection leg numbness
 0 0 0
% Working Pre-operatively 80 65 75
% Working Post-operatively 80 65 75
Open in a new tab

HNP = herniated Nucleus Pulposus, SS = spinal stenosis, DDD = degenerative disc disease.

3.1. Adverse events

There were no complications or other adverse effects. Specifically, there was no unusual pain at the injection site; postural headache in the setting of inadvertent dural puncture; redness, swelling, bleeding, or infection at the needle insertion site; temporary weakness from local anesthetic block; allergic reactions to the contrast dye, local anesthetic, or antimicrobial skin prep; infection, seizure, epidural hemorrhage, vaso-vagal reactions, or emergency room visits. All preoperative neurological deficits ultimately resolved.

3.2. Outcomes

Within the HNP group, there was a significant decrease in low back and leg pain that was sustained at all follow-up periods (LBP all at p < 0.0001, and leg all at p < 0.004), Fig. 1, Fig. 2. Pain drawing improved significantly at all follow-up periods (p < 0.002) except at 3–4 months, Fig. 3. ODI improved significantly at all follow-up periods (p < 0.01), Fig. 4. The PROMIS physical component improved significantly at all follow-up periods after 3 months (p = 0.02). The PROMIS mental component improved significantly only at the 3–4 month period (p = 0.015 but at a low power of <0.6). The Global Physical and Mental scores had similar significance as the PROMIS scores, Fig. 5, Fig. 6.

Fig. 1.

Fig. 1

Open in a new tab

Back pain.

Fig. 2.

Fig. 2

Open in a new tab

Leg pain.

Fig. 3.

Fig. 3

Open in a new tab

Pain drawing.

Fig. 4.

Fig. 4

Open in a new tab

OSWESTRY disability.

Fig. 5.

Fig. 5

Open in a new tab

PROMIS physical health.

Fig. 6.

Fig. 6

Open in a new tab

PROMIS mental health.

Within the SS group, there was a significant decrease in low pain at first 3 follow-up periods (p < 0.012) and decreased leg back pain at all follow-up (all at p < 0.022). Pain drawing improved significantly at the two early follow-up periods (p < 0.005) except at 3–4 months. ODI improved significantly at all follow-up periods (p < 0.026). The PROMIS physical and Global Physical components improved significantly at all follow-up periods (p < 0.03). The PROMIS mental and Global Mental scores had had no significant improvement.

Within the DDD group, there was a significant decrease in low back pain at all follow-up periods (all p < 0.007). No other outcomes had significant improvement except for the ODI at the initial 2–3 week follow-up period (p = 0.027).

Comparing the groups, it was found that prior to AF injection, all pain/disability scores were similar except that the Global Physical components score for HNP was worse than for SS (p = 0.011). A refined analysis found at baseline, in the HNP group, one patient denied back and 2 denied leg pain. In the SS group, all but one patient had leg pain; but in the DDD group, 7 patients denied leg pain. After the AF injection, the HNP patients had the greatest initial reduction in symptoms with average LBP VAS improvement from 6.3 to 2.9, which was significant greater improvement relative to the other 2 groups (p = 0.035), leg VAS from 5.9 to 2.5, and ODI from 37 to 19 and was significant at all follow-up periods. SS patients had LBP VAS improvement from 6.8 to 5.8, and leg VAS improvement from 5.8 to 3.1 which was significantly greater than that for DDD improvement (p = 0.045), and ODI improvement from 46 to 33 and was significant at all follow-up periods (Fig. 1, Fig. 2, Fig. 3, Fig. 4). DDD patients had LBP VAS improvement from 7.0 to 4.6 which was significant at all follow-up periods, but significant improvements in leg VAS and ODI did not last beyond the first follow-up. Between groups, HNP and SS had significantly greater ODI improvement than the DDD group after the 3 month follow-up (all p < 0.03). PROMIS score changes were not significantly different between the groups except the Global mental health improvements was greater for HNP and SS relative to DDD (p = 0.038).

The HNP group reduced opioid use significantly from 45 % to 10 % (p < 0.016 at all follow-up periods) and reduced non-opioid medication use significantly from 80 % to 45 % (p < 0.040 at all follow-up time periods). SS reduced opioid use from 30 % to 25 % and reduced non-opioid medications from 60 % to 55 % which were not significant improvements. DDD reduced opioids from 50 % to 35 % and reduced non-opioid medications from 55 % to 40 % which were not significant improvements. At any given postoperative period, there was no significant difference in pain medication use between the groups.

3.3. Assessment of success

Success was quantitated by determining the rate for each diagnostic group at 3 follow-up time periods, 3–4 months, 6–8 months and 10–14 months. One method calculated the rate of those obtaining MCID and the other by a 50 % reduction of VAS and ODI measures. The HNP group had the greatest rate of obtaining MCID or greater improvement for Back and Leg Pain VAS and ODI scores, which was significantly greater relative to both SS and DDD groups over all follow-up periods for the ODI measure (all p < 0.01, Fig. 7, Fig. 8, Fig. 9). HNP had a strong trend to greater rate of attaining MCID for leg pain reduction relative to DDD (p = 0.056). Success as defined by a 50 % reduction in VAS and ODI measures found a significantly greater rate for HNP relative to both SS and DDD groups over all follow-up periods for the ODI measure (all < p = 0.05, Fig. 10, Fig. 11, Fig. 12).

Fig. 7.

Fig. 7

Open in a new tab

Back pain VAS MCID.

Fig. 8.

Fig. 8

Open in a new tab

leg pain VAS MCID

Fig. 9.

Fig. 9

Open in a new tab

ODI MCID

Fig. 10.

Fig. 10

Open in a new tab

Back pain success.

Fig. 11.

Fig. 11

Open in a new tab

Leg pain success.

Fig. 12.

Fig. 12

Open in a new tab

ODI success.

Patient's global self-perception of treatment success was initially 70 %, 50 %, and 50 % for the HNP, SS, and DDD groups respectively which was statistically similar. At the final follow-up, success was 65 %, 35 %, and 50 % for the HNP, SS, and DDD groups respectively which was statistically similar. When patients were queried as to if they would repeat an AF injection, positive responses in the early follow-up periods were 75 %, 65 % and 70 % for the HNP, SS, and DDD groups respectively which was statistically similar. At the final follow-up, repeat injection willingness was 70 %, 35 %, and 70 % for the HNP, SS, and DDD groups respectively which was statistically greater for the HNP and DDD compared to SS group (p = 0.035 at all follow-up time periods). Recommending the treatment to others was highest in the HNP group with a positive response 70 %–80 % throughout the follow-up periods. SS patients recommended the treatment to others initially at 60 % but declined to 35 % over time. DDD patients recommended the treatment to others at 50 %–70 % over the course of the study.

Return to work was also evaluated before and after treatment with AF epidural injections. For the HNP group 16 of 20 patients (80 %) were employed prior to AF of which all were able to return to work. For the SS group 13 of 20 patients (65 %) were employed prior to AF of which all were able to return to work but one returned at a light duty capacity. For the DDD group 15 of 20 patients (75 %) were employed prior to AF of which all were able to return to work but 2 returned at a light duty capacity.

3.4. Additional treatments

Of the patients that failed the epidural AF injection, some had additional injections (ESI, facet injections, or sacroiliac injections) or surgery. Two HNP patients had additional injections; one had a second AF injection and one an ESI. Six SS patients had additional injections; 2 had a second AF, 3 an ESI, and one facet injections. Two DDD patients had additional ESI. Surgical intervention included 6 HNP patients; 3 had discectomy/decompression and another 3 had a TDR (total disc replacement) or fusion. The HNP patients had their surgeries at various post injection periods: 2 at 4 months, 3 at 7 months and 1 at 12 months after AF injection. 3 SS patients had decompression (1 at 2, 1 at 3, and 1 at 4 months after AF injection) of which one eventually also went on to have a fusion; and 7 DDD patients had fusion or TDR (4 at 5, 1 at 9, 1 at 10, and 1 at 12 months after AF injection) and another had a TDR shortly after the final one year follow-up period. Confounding factors were also tracked and included patients with multi-level conditions, new injuries, and variable opioid tolerance. Multiple level disc degeneration was most notable for the SS group, Table 1.

4. Discussion

The present study is the first, that we know of, to demonstrate the effects of epidural AF in spinal applications. The safety of AF in the epidural space was confirmed for our patients and complements other studies that have shown no adverse effects of placental allografts used in the treatment of spinal conditions including contact with nervous tissue [[45], [46], [47]]. The present study also demonstrated reduced pain and disability in patients with LBP related to three common degenerative conditions. Specifically, the HNP group had the greatest improvement in patient reported outcomes on multiple scales (VAS back and leg pain, Pain Drawing, ODI, PROMIS) and decreased use of pain medication. Success, as defined by attaining MCID or greater than 50 % improvement, favored the HNP group for all 3 criteria, although SS had similar Success for leg pain. The ODI improvement was significantly greater for the HNP relative to both SS and DDD groups for both MCID and Success. The HNP group also had the highest rate of self-assessed success. The SS group had improved PROMS and was most notable for leg pain improvement. The DDD group had the least improvement in PROMS and the highest rate of patients having surgical intervention within a year of the AF injection. Generally, leg pain was reduced in those with a large component of leg pain prior to AF injection.

In general, many patients will recover from back pain without surgery. Often, conservative management, including oral medications, chiropractic/physical therapy, and anesthetic and/or steroid injections, are attempted before proceeding to surgery. The use of anti-inflammatory agents in the treatment of spinal conditions has been advocated as a non-operative approach. NSAIDS and oral steroids have long been used as a form of medical treatment. In general, HNP, SS, and DDD have an inflammatory component producing pain symptoms. Most often, this originates from the intervertebral disc. Basic scientific studies have identified enzymes and inflammatory mediators in degenerated disc tissue specimens. Specifically, disc specimens have been found to contain elevated levels of enzymes capable of degrading protein within the disc, such as matrix metalloproteinase [[48], [49], [50], [51]]. Cytokines, nitric oxide, and inflammatory mediators have also been found to be elevated [[50], [51], [52], [53], [54], [55]]. The inflammation induced by cytokines is thought to include TNF-alpha and interleukins, such as IL1α, IL-6 and IL-8 [55]. Thus, one may, in general, rationalize the use of potent anti-inflammatory agents to counter the above inflammatory mediators. Historically, steroids have been used because of their anti-inflammatory properties in the treatment of discogenic pain [56,57]. Higher concentrations of an anti-inflammatory agent may be achieved with localized application by way of epidural injections. Interventional treatment, particularly, epidural injections have been used for lumbar HNP, SS, and DDD.

Lumbar intervertebral disc herniation is characterized by incompetence of the disc, usually the annulus fibrosis. Symptoms may be from an annular tear that allows leakage of cytokines from the nucleus to enter the epidural space and irritate the nerve roots, or a large annular tear may result in an extruded portion of the nucleus into the epidural space [58]. In both cases, this may produce radiculopathy (sensory or motor neurological deficits) and radicular pain (radiculitis). Radiculopathy is thought to result from both mechanical compression, and cytokine-mediated inflammation producing radiculitis and nerve root swelling. Stenosis is a more gradual process of nerve root encroachment, often due to progressive hypertrophy of the facet joints and ligamentum flavum and may also be combined with a spondylolisthesis or broad-based disc herniation. Since the nerve roots have little room within a narrow canal, even slight perturbation from instability or discogenic inflammation/annular disruption may produce symptoms. DDD is a leading reason for low back pain and is thought to be due to annular tears that allow intradiscal inflammatory agents to leak into the epidural space which then may irritate nervous structures despite no actual compression to the nerve roots. Patients with inflammatory endplate changes (Modic I changes identified on MRI) are particularly painful [59,60]. It should be noted that in the present study, the DDD patients with these endplate changes were not specifically studied.

The most common epidural injection is with a steroid. Meta-analyses have demonstrated significant improvements in pain, functionality, and disability following ESI in patients with sciatica, at least for the first few months after the procedure [61,62]. For radicular pain associated with lumbar HNP, ESI may decrease the rate of surgical intervention in addition to reducing symptoms [63,64]. SS is also often treated with ESI, and studies have found improved outcomes. One multicenter clinical trial of SS patients demonstrated improvement with ESI but no significant difference between epidural injection of corticosteroid and lidocaine combined vs lidocaine alone in terms of patient reported improvements in leg pain and disability at 6 weeks after injection [65]. Thus, patients with spinal stenosis may be more refractory to treatment with epidural steroids than those with symptomatic disc herniation. ESI in DDD patients is also recommended as an option in highly symptomatic patients in lieu of surgery [66]. The degree of improvement after ESI can vary and may depend upon the condition being treated, with DDD having the least responsiveness [7,67]. Similarly, the current study of epidural AF also found the DDD group to have the least improvement in pain and functional after AF injection.

Limitations include the small sample size of each group as the morphology of each condition has wide variability. Pain is also subjective, and confounding factors (other concurrent nonoperative treatments, activities, psychosocial environment, etc) may contribute to patient responses to outcomes measures. Another limitation is that facet joint mediated pain was not rigorously excluded in all patients for practical reasons.

5. Conclusion

AF epidural injections seem to be safe, and have similar clinical results to prior reports of ESI for the 3 spinal conditions treated in this study. The effectiveness of AF may have a longer duration than for steroid. The preliminary data obtained in this study indicates the most appropriate indication for epidural AF are HNP followed by SS, of which both groups had significant pre-injection leg symptoms. Furthermore, it forms the basis for an upcoming prospective randomized comparative study of epidural AF to epidural steroid injections. Based on the results of this pilot study, further evaluation, such as a comparative study is best suited for HNP and possibly SS patients. Future studies could also be comparative to control groups treated with saline placebo or local anesthetic only since these sham control groups may have a subjective effect on PROMs [60,63]. AF epidural injection studies need a rigorous evaluation similar to that for platelet rich plasma epidural injections with reports of success comparable to steroid injections [66,68].

Declaration of generative AI and AI-assisted technologies in the writing process

None were used and are not applicable to this manuscript.

Source of funding

Self-funded by Midwest Spine & Brain Institute.

Conflict of interest statement

None of the authors have a conflict of interest in relationship to this study.

References

  • 1.Koes B.W., van Tulder M., Lin C.W., Macedo L.G., McAuley J., Maher C. An updated overview of clinical guidelines for the management of non-specific low back pain in primary care. Eur Spine J. 2010 Dec;19(12):2075–2094. doi: 10.1007/s00586-010-1502-y. Epub 2010 Jul 3. PMID: 20602122; PMCID: PMC2997201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Ko S., Kim S., Kim J., Oh T. The effectiveness of oral corticosteroids for management of lumbar radiating pain: randomized, controlled trial study. Clin Orthop Surg. 2016 Sep;8(3):262–267. doi: 10.4055/cios.2016.8.3.262. Epub 2016 Aug 10. PMID: 27583108; PMCID: PMC4987309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Oliveira C.B., Maher C.G., Pinto R.Z., Traeger A.C., Lin C.C., Chenot J.F., van Tulder M., Koes B.W. Clinical practice guidelines for the management of non-specific low back pain in primary care: an updated overview. Eur Spine J. 2018 Nov;27(11):2791. doi: 10.1007/s00586-018-5673-2. 267. Epub 2018 Jul 3. PMID: 29971708. [DOI] [PubMed] [Google Scholar]
  • 4.Gegel B.T., Floyd J.P., 4th, Hart D.W., Barnhill W.K., Maye J.P. A review of the analgesic benefits and potential complications related to epidural corticosteroid injections. AANA J (Am Assoc Nurse Anesth) 2019 Feb;87(1):71–79. [PubMed] [Google Scholar]
  • 5.Lee J.H., Kim D.H., Kim D.H., Shin K.H., Park S.J., Lee G.J., Lee C.H., Yang H.S. Comparison of clinical efficacy of epidural injection with or without steroid in lumbosacral disc herniation: a systematic review and meta-analysis. Pain Physician. 2018 Sep;21(5):449–468. [PubMed] [Google Scholar]
  • 6.Smith C.C., McCormick Z.L., Mattie R., MacVicar J., Duszynski B., Stojanovic M.P. The effectiveness of lumbar transforaminal injection of steroid for the treatment of radicular pain: a comprehensive review of the published data. Pain Med. 2020 Mar 1;21(3):472–487. doi: 10.1093/pm/pnz160. [DOI] [PubMed] [Google Scholar]
  • 7.Buttermann G.R. The effect of spinal steroid injections for degenerative disc disease. Spine J. 2004;4(5):495–505. doi: 10.1016/j.spinee.2004.03.024. [DOI] [PubMed] [Google Scholar]
  • 8.Bicket M.C., Horowitz J.M., Benzon H.T., Cohen S.P. Epidural injections in prevention of surgery for spinal pain: systematic review and meta-analysis of randomized controlled trials. Spine J. 2015 Feb 1;15(2):348–362. doi: 10.1016/j.spinee.2014.10.011. [DOI] [PubMed] [Google Scholar]
  • 9.Koltsov J.C.B., Smuck M.W., Zagel A., Alamin T.F., Wood K.B., Cheng I., Hu S.S. Lumbar epidural steroid injections for herniation and stenosis: incidence and risk factors of subsequent surgery. Spine J. 2019 Feb;19(2):199–205. doi: 10.1016/j.spinee.2018.05.034. PMID:29959098. [DOI] [PubMed] [Google Scholar]
  • 10.Ingawale D.K., Mandlik S.K., Patel S.S. An emphasis on molecular mechanisms of anti-inflammatory effects and glucocorticoid resistance. J Compl Integr Med. 2015 Mar;12(1):1–13. doi: 10.1515/jcim-2014-0051. [DOI] [PubMed] [Google Scholar]
  • 11.Rhen T., Cidlowski J.A. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711–1723. doi: 10.1056/NEJMra050541. PMID: 16236742. [DOI] [PubMed] [Google Scholar]
  • 12.Weinstein R.S. Glucocorticoid-induced osteonecrosis. Endocrine. 2012;41(2):183–190. doi: 10.1007/s12020-011-9580-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Stout A., Friedly J., Standaert C.J. Systemic absorption and side effects of locally injected glucocorticoids. Pharm Manag PM R. 2019 Apr;11(4):409–419. doi: 10.1002/pmrj.12042. [DOI] [PubMed] [Google Scholar]
  • 14.Skalka H.W., Prchal J.T. Effect of corticosteroids on cataract formation. Arch Ophthalmol. 1980 Oct;98(10):1773–1777. doi: 10.1001/archopht.1980.01020040625007. PMID: 7425901. [DOI] [PubMed] [Google Scholar]
  • 15.Yang S., Werner B.C., Cancienne J.M., Hassanzadeh H., Shimer A.L., Shen F.H., Singla A. Preoperative epidural injections are associated with increased risk of infection after single-level lumbar decompression. Spine J. 2016 Feb;16(2):191–196. doi: 10.1016/j.spinee.2015.07.439. [DOI] [PubMed] [Google Scholar]
  • 16.Willett N.J., Thote T., Lin A.S., et al. Intra-articular injection of micronized dehydrated human amnion/chorion membrane attenuates osteoarthritis development. Arthritis Res Ther. 2014;16(1) doi: 10.1186/ar4476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Farr J., Gomoll A.H., Yanke A.B., Strauss E.J., Mowry K.C., ASA Study Group A randomized controlled single-blind study demonstrating superiority of amniotic suspension allograft injection over hyaluronic acid and saline control for modification of knee osteoarthritis symptoms. J Knee Surg. 2019 Nov;32(11):1143–1154. doi: 10.1055/s-0039-1696672. [DOI] [PubMed] [Google Scholar]
  • 18.Luo T.D., Vines J.B., Zabarsky Z.K., Mowry K.C., Marquez-Lara A., Jinnah A.H., Ma X., Berwick B.W., Willey J.S., Smith T.L., Li Z., O'Gara T.J. Evaluation of percutaneous intradiscal amniotic suspension allograft in a rabbit model of intervertebral disc degeneration. Spine. 2018 Mar 15;44(6):E329–E337. doi: 10.1097/BRS.0000000000002851. [DOI] [PubMed] [Google Scholar]
  • 19.Karaçal N., Koşucu P., Cobanglu U., Kutlu N. Effect of human amniotic fluid on bone healing. J Surg Res. 2005 Dec;129(2):283–287. doi: 10.1016/j.jss.2005.03.026. [DOI] [PubMed] [Google Scholar]
  • 20.Kerimoğlu S., Livaoğlu M., Sönmez B., Yuluğ E., Aynaci O., Topbas M., Yarar S. Effects of human amniotic fluid on fracture healing in rat tibia. J Surg Res. 2009 Apr;152(2):281–287. doi: 10.1016/j.jss.2008.02.028. Epub 2008 Mar 18. PMID:18499130. [DOI] [PubMed] [Google Scholar]
  • 21.Özgenel G.Y., Şamli B., Özcan M. Effects of human amniotic fluid on peritendinous adhesion formation and tendon healing after flexor tendon surgery in rabbits. March 2001;26(2):332–339. doi: 10.1053/jhsu.2001.22524. [DOI] [PubMed] [Google Scholar]
  • 22.Mrugala A., Sui A., Plummer M., Altman I., Papineau E., Frandsen D., Hill D., Ennis W.J. Amniotic membrane is a potential regenerative option for chronic non-healing wounds: a report of five cases receiving dehydrated human amnion/chorion membrane allograft. Int Wound J. 2016 Aug;13(4):485–492. doi: 10.1111/iwj.12458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Quinto G.G., Camacho W., Castro-Combs J., Li L., Martins S.A., Wittmann P., Campos M., Behrens A. Effects of topical human amniotic fluid and human serum in a mouse model of keratoconjunctivitis sicca. Cornea. 2012 Apr;31(4):424–430. doi: 10.1097/ICO.0b013e31823f0a64. [DOI] [PubMed] [Google Scholar]
  • 24.Penny H., Rifkah M., Weaver A., et al. Dehydrated human amnion/chorion tissue in difficult-to-heal DFUs: a case series. J Wound Care. 2015;24(3):104. doi: 10.12968/jowc.2015.24.3.104. [DOI] [PubMed] [Google Scholar]
  • 25.Zelen C.M., Snyder R.J., Serena T.E. Li WW the use of human amnion/chorion membrane in the clinical setting for lower extremity repair: a review. Clin Podiatr Med Surg. 2015 Jan;32(1):135–146. doi: 10.1016/j.cpm.2014.09.002. [DOI] [PubMed] [Google Scholar]
  • 26.Zelen C.M., Gould L., Serena T.E., Carter M.J., Keller J., Li W.W. A prospective, randomized, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers. Int Wound J. 2015 Dec;12(6):724–732. doi: 10.1111/iwj.12395. PMID:25424146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Underwood M.A., Gilbert W.M., Sherman M.P. Amniotic fluid: not just fetal urine anymore. J Perinatol. 2005 May;25(5):341–348. doi: 10.1038/sj.jp.7211290. [DOI] [PubMed] [Google Scholar]
  • 28.Greig P.C., Herbert W.N., Robinette B.L., Teot L.A. Amniotic fluid interleukin-10 concentrations increase through pregnancy and are elevated in patients with preterm labor associated with intrauterine infection. Am J Obstet Gynecol. 1995 Oct;173(4):1223–1227. doi: 10.1016/0002-9378(95)91358-0. PMID: 7485325. [DOI] [PubMed] [Google Scholar]
  • 29.Harmon K.A., Kimmerling K.A., Mowry K.C. Effect of amniotic suspension allograft in a rat destabilization of medial meniscus osteoarthritis model. J Orthop Res. 2024 Oct;42(10):2159–2171. doi: 10.1002/jor.25872. Epub 2024 May 23. PMID: 38779982. [DOI] [PubMed] [Google Scholar]
  • 30.Kimmerling K.A., Gomoll A.H., Farr J., Mowry K.C. Amniotic suspension allograft modulates inflammation in a rat pain model of osteoarthritis. J Orthop Res. 2020 May;38(5):1141–1149. doi: 10.1002/jor.24559. Epub 2019 Dec 19. PMID: 31814175; PMCID: PMC7187262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Korkmaz V., Cekmez Y., Surer H., Deveci C.D., Ocal F.D., Gezer M., Kurdoglu Z., Ergun Y., Kucukozkan T. Comparison of amniotic fluid cytokine levels in postterm and term pregnancy: a prospective study. Clin Lab. 2017 Feb 1;63(2):235–240. doi: 10.7754/Clin.Lab.2016.160711. [DOI] [PubMed] [Google Scholar]
  • 32.Maymon E., Romero R., Pacora P., Gomez R., Mazor M., Edwin S., Chaiworapongsa T., Kim J.C., Yoon B.H., Menon R., Fortunato S., Berry S.M. A role for the 72 kDa gelatinase (MMP-2) and its inhibitor (TIMP-2) in human parturition, premature rupture of membranes and intraamniotic infection. J Perinat Med. 2001;29(4):308–316. doi: 10.1515/JPM.2001.044. [DOI] [PubMed] [Google Scholar]
  • 33.McQuilling J.P., Vines J.B., Kimmerling K.A., et al. Proteomic comparison of amnion and chorion and evaluation of the effects of processing on placental membranes. Wounds. 2017;29:E38–E42. [PMC free article] [PubMed] [Google Scholar]
  • 34.Michaels J.E., Dasari S., Pereira L., Reddy A.P., Lapidus J.A., Lu X., Jacob T., Thomas A., Rodland M., Roberts C.T., Jr., Gravett M.G., Nagalla S.R. Comprehensive proteomic analysis of the human amniotic fluid proteome: gestational age-dependent changes. J Proteome Res. 2007 Apr;6(4):1277–1285. doi: 10.1021/pr060543t. [DOI] [PubMed] [Google Scholar]
  • 35.Burns C., Hall S.T., Smith R., Blackwell C. Cytokine levels in late pregnancy: are female infants better protected against inflammation? Front Immunol. 2015 Jun 16;6:318. doi: 10.3389/fimmu.2015.00318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Pierce J., Jacobson P., Benedetti E., Peterson E., Phibbs J., Preslar A., Reems J.A. Collection and characterization of amniotic fluid from scheduled C-section deliveries. Cell Tissue Bank. 2016 Sep;17(3):413–425. doi: 10.1007/s10561-016-9572-7. [DOI] [PubMed] [Google Scholar]
  • 37.Trentini A., Maritati M., Cervellati C., Manfrinato M.C., Gonelli A., Volta C.A., Vesce F., Greco P., Dallocchio F., Bellini T., Contini C. Vaginal lactoferrin modulates PGE2, MMP-9, MMP-2, and TIMP-1 amniotic fluid concentrations. Mediat Inflamm. 2016;2016 doi: 10.1155/2016/3648719. PMCID: PMC5107848, PMID: 27872513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Fukuda H., Masuzaki H., Ishimaru T. Interleukin-6 and interleukin-1 receptor antagonist in amniotic fluid and cord blood in patients with pre-term, premature rupture of the membranes. Int J Gynaecol Obstet. 2002 May;77(2):123–129. doi: 10.1016/s0020-7292(02)00016-4. PMID: 12031562. [DOI] [PubMed] [Google Scholar]
  • 39.Apuzzio J., Chan Y., Al-Khan A., Illsley N., Kim P.L., Vonhaggen S. Second-trimester amniotic fluid interleukin-10 concentration predicts preterm delivery. J Matern Fetal Neonatal Med. 2004 May;15(5):313–317. doi: 10.1080/14767050410001702186. PMID: 15280122. [DOI] [PubMed] [Google Scholar]
  • 40.Romero R., Gomez R., Galasso M., Mazor M., Berry S.M., Quintero R.A., Cotton D.B. The natural interleukin-1 receptor antagonist in the fetal, maternal, and amniotic fluid compartments: the effect of gestational age, fetal gender, and intrauterine infection. Am J Obstet Gynecol. 1994 Oct;171(4):912–921. doi: 10.1016/s0002-9378(94)70058-3. PMID: 7943101. [DOI] [PubMed] [Google Scholar]
  • 41.Michalik A.J., Patel R.K. Evaluation of transforaminal epidural steroid injections for discogenic axial lumbosacral back pain utilizing PROMIS as an outcome measure. Spine J. 2021 Feb;21(2):202–211. doi: 10.1016/j.spinee.2020.10.018. Epub 2020 Oct 20. PMID: 33091610. [DOI] [PubMed] [Google Scholar]
  • 42.Vaishnav A.S., McAnany S.J., Iyer S., Albert T.J., Gang C.H., Qureshi S.A. Psychometric evaluation of patient-reported outcomes measurement information System physical function computer adaptive testing in minimally invasive lumbar spine surgery: an analysis of responsiveness, coverage, discriminant validity, and concurrent validity. J Am Acad Orthop Surg. 2020 Sep 1;28(17):717–729. doi: 10.5435/JAAOS-D-19-00306. PMID: 32833390. [DOI] [PubMed] [Google Scholar]
  • 43.Ostelo R.W., Deyo R.A., Stratford P., Waddell G., Croft P., Von Korff M., Bouter L.M., de Vet H.C. Interpreting change scores for pain and functional status in low back pain: towards international consensus regarding minimal important change. Spine. 2008 Jan 1;33(1):90–94. doi: 10.1097/BRS.0b013e31815e3a10. PMID: 18165753. [DOI] [PubMed] [Google Scholar]
  • 44.Nagpal A.S., Vu T.N., Gill B., Conger A., McCormick Z.L., Duszynski B., Boies B.T. Systematic review of the effectiveness of caudal epidural steroid injections in the treatment of chronic low back or radicular pain. Interv Pain Med. 2022 Oct 3;1(4) doi: 10.1016/j.inpm.2022.100149. PMID: 39238877; PMCID: PMC11373049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Tao H., Fan H. Implantation of amniotic membrane to reduce postlaminectomy epidural adhesions. Eur Spine J. 2009;18(8):1202–1212. doi: 10.1007/s00586-009-1013-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Subach B.R., Copay A.G. The use of a dehydrated amnion/chorion membrane allograft in patients who subsequently undergo reexploration after posterior lumbar instrumentation. Adv Orthop. 2015;2015 doi: 10.1155/2015/501202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Anderson D.G., Popov V., Raines A.L., O'Connell J. Cryopreserved amniotic membrane improves clinical outcomes following microdiscectomy. Clin Spine Surg. 2017 Nov;30(9):413–418. doi: 10.1097/BSD.0000000000000544. [DOI] [PubMed] [Google Scholar]
  • 48.Fujita K., Nakagawa T., Hirabayashi K., Nagai Y. Neural proteinases in human intervertebral disc: role in degeneration and probable origin. Spine. 1993;18(13):1766–1773. doi: 10.1097/00007632-199310000-00009. [DOI] [PubMed] [Google Scholar]
  • 49.Goupille P., Jayson M.I.V., Valat J.-P., Freemont A.J. Matrix metalloproteinases: the clue to intervertebral disc degeneration? Spine. 1998;23(14):1612–1626. doi: 10.1097/00007632-199807150-00021. [DOI] [PubMed] [Google Scholar]
  • 50.Kanemoto M., Hukuda S., Komiya Y., et al. Immunohistochemical study of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 in human intervertebral discs. Spine. 1996;21(1):1–8. doi: 10.1097/00007632-199601010-00001. [DOI] [PubMed] [Google Scholar]
  • 51.Kang J.D., Georgescu H.I., McIntyre-Larkin L., et al. Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2. Spine. 1996;21(3):271–277. doi: 10.1097/00007632-199602010-00003. [DOI] [PubMed] [Google Scholar]
  • 52.Liu J., Roughley P.J., Mort J.S. Identification of human intervertebral disc stromelysin and its involvement in matrix degradation. J Orthop Res. 1991;9:568–575. doi: 10.1002/jor.1100090413. [DOI] [PubMed] [Google Scholar]
  • 53.Nemoto O., Yamagishi M., Kukuchi T., Ozeki Y., Shinmei M. The effects of IL-1 and IL-6 on the production of MMP-3 and TIMP-1 in human degenerative spinal disc. Rinsho Seikeigeka. 1994;29:369–374. [Google Scholar]
  • 54.Saal J.S., Franson R.C., Dobrow R., Saal J.A., et al. High levels of inflammatory phospholipase A2 activity in lumbar disc herniations. Spine. 1990 Jul;15(7):674–678. doi: 10.1097/00007632-199007000-00011. [DOI] [PubMed] [Google Scholar]
  • 55.Takahashi H., Suguro T., Okazima Y., Motegi M., Okada Y., Kakiuchi T. Inflammatory cytokines in the herniated disc of the lumbar spine. Spine. 1996 Jan 15;21(2):218–224. doi: 10.1097/00007632-199601150-00011. PMID: 8720407. [DOI] [PubMed] [Google Scholar]
  • 56.Hargreaves K.M., Swift J.Q., Roszkowski M.T., et al. Pharmacology of peripheral neuropeptide and inflammatory mediator release. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1994;10:503–510. doi: 10.1016/0030-4220(94)90045-0. [DOI] [PubMed] [Google Scholar]
  • 57.Moroney P.J., Watson R.W.G., Burke J.G., et al. PH and anti-inflammatory agents modulate nucleus pulposus cytokine secretion. Spine J. 2002;2:49S–50S. [Google Scholar]
  • 58.Saal J.A. Natural history and nonoperative treatment of lumbar disc herniation. Spine. 1996 Dec 15;21(24 Suppl):2S–9S. doi: 10.1097/00007632-199612151-00002. PMID: 9112320. [DOI] [PubMed] [Google Scholar]
  • 59.Czaplewski L.G., Rimmer O., McHale D., Laslett M. Modic changes as seen on MRI are associated with nonspecific chronic lower back pain and disability. J Orthop Surg Res. 2023 May 12;18(1):351. doi: 10.1186/s13018-023-03839-w. PMID: 37170132; PMCID: PMC10176889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Rahme R., Moussa R. The modic vertebral endplate and marrow changes: pathologic significance and relation to low back pain and segmental instability of the lumbar spine. AJNR Am J Neuroradiol. 2008 May;29(5):838–842. doi: 10.3174/ajnr.A0925. Epub 2008 Feb 13. PMID: 18272564; PMCID: PMC8128601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Verheijen E.J.A., Bonke C.A., Amorij E.M.J., Vleggeert-Lankamp C.L.A. Epidural steroid compared to placebo injection in sciatica: a systematic review and meta-analysis. Eur Spine J. 2021 Nov;30(11):3255–3264. doi: 10.1007/s00586-021-06854-9. Epub 2021 May 11. PMID: 33974132. [DOI] [PubMed] [Google Scholar]
  • 62.Oliveira C.B., Maher C.G., Ferreira M.L., Hancock M.J., Oliveira V.C., McLachlan A.J., Koes B.W., Ferreira P.H., Cohen S.P., Pinto R.Z. Epidural corticosteroid injections for lumbosacral radicular pain. Cochrane Database Syst Rev. 2020 Apr 9;4(4) doi: 10.1002/14651858.CD013577. PMID: 32271952; PMCID: PMC7145384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Zhang J., Zhang R., Wang Y., Dang X. Efficacy of epidural steroid injection in the treatment of sciatica secondary to lumbar disc herniation: a systematic review and meta-analysis. Front Neurol. 2024 May 22;15 doi: 10.3389/fneur.2024.1406504. PMID: 38841695; PMCID: PMC11150834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Buttermann G.R. Treatment of lumbar disc herniation: epidural steroid injection compared with discectomy, A prospective randomized study. J Bone Joint Surg. 2004;86A:670–679. [PubMed] [Google Scholar]
  • 65.Friedly J.L., Comstock B.A., Turner J.A., et al. A randomized trial of epidural glucocorticoid injections for spinal stenosis. N Engl J Med. 2014;371(1):11–21. doi: 10.1056/NEJMoa1313265. [DOI] [PubMed] [Google Scholar]
  • 66.Fang Z., Yuan C., Cheng L., Yao Q., Zhang C., Wang X., Guan J., Jian F. Comparison of clinical efficacy of epidural injection with or without steroids in the treatment of degenerative disc disease: meta-analysis. Pain Physician. 2022 Mar;25(2):145–160. PMID: 35322968. [PubMed] [Google Scholar]
  • 67.Manchikanti L., Buenaventura R.M., Manchikanti K.N., Ruan X., Gupta S., Smith H.S., Christo P.J., Ward S.P. Effectiveness of therapeutic lumbar transforaminal epidural steroid injections in managing lumbar spinal pain. Pain Physician. 2012 May-Jun;15(3):E199–E245. PMID: 22622912. [PubMed] [Google Scholar]
  • 68.Muthu S., Viswanathan V.K., Gangadaran P. Is platelet-rich plasma better than steroids as epidural drug of choice in lumbar disc disease with radiculopathy? Meta-analysis of randomized controlled trials. Exp Biol Med (Maywood) 2025 Feb 4;250 doi: 10.3389/ebm.2025.10390. PMID: 39968415; PMCID: PMC11832311. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Interventional Pain Medicine are provided here courtesy of Elsevier

RESOURCES