European Spine Journal

https://doi.org/10.1007/s00586-023-08064-x

ORIGINAL ARTICLE

The impact of novel inflammation‑preserving treatment

towards lumbar disc herniation resorption in symptomatic patients:
a prospective, multi‑imaging and clinical outcomes study
Hanne B. Albert1,2 · Arash J. Sayari1,3 · J. Nicolas Barajas1,2 · Alexander L. Hornung1,2 · Garrett Harada1,2 ·
Michael T. Nolte1,2 · Ana V. Chee1,2 · Dino Samartzis1,2 · Alexander Tkachev4

Received: 24 September 2021 / Revised: 18 November 2023 / Accepted: 22 November 2023

© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023

Abstract
Purpose We performed a prospective one-year multi-imaging study to assess the clinical outcomes and rate of disc resorption
in acute lumbar disc herniation (LDH) patients undergoing inflammation-preserving treatment (i.e. no NSAIDS, steroids).
Methods All patients received gabapentin to relieve leg pain, 12 sessions of acupuncture. Repeat MRI was performed, every
3 months, after 12 sessions of treatment continued for those without 40% reduction in herniated disc sagittal area. Disc
herniations sizes were measured on sagittal T2W MRI sequences, pre-treatment and at post-treatment intervals. Patients
were stratified to fast, medium, slow, and prolonged recovery groups in relation to symptom resolution and disc resorption.
Results Ninety patients (51% females; mean age: 48.6 years) were assessed. Mean size of disc herniation was
119.54 ± 54.34 ­mm2, and the mean VAS-Leg score was 6.12 ± 1.13 at initial presentation. A total of 19 patients (21.1%)
improved at the time of the repeat MRI (i.e. within first 3 months post-treatment). 100% of all patient had LDH resorption
within one year (mean: 4.4. months). There was no significant difference at baseline LDH between fast, medium, slow, and
prolonged resorption groups. Initial LDH size was weakly associated with degree of leg pain at baseline and initial gabapentin
levels. Surgery was avoided in all cases.
Conclusion This is the first study to note inflammation-preserving treatment, without conventional anti-inflammatory and
steroid medications, as safe and effective for patients with an acute LDH. Rate of disc resorption (100%) was higher than
comparative recent meta-analysis findings (66.7%) and no patient underwent surgery.

Keywords Resorption · Disc · Spine · Lumbar · Herniation · Degeneration · Regression · Resorption · Treatment · Healing

Introduction

Low back pain (LBP) is currently the world’s leading cause

of pain and disability, imposing a costly burden to healthcare
systems, patients, and society [1]. Frequently, LBP is asso-
* Hanne B. Albert ciated with an acute lumbar disc herniation (LDH) causing
modicklinikken@modicklinikken.dk
spinal nerve root compression which normally presents with
* Dino Samartzis leg pain, back pain, or both. Current guidelines published by
Dino_Samartzis@rush.edu
the North American Spine Society recommend a minimum
1
Department of Orthopedic Surgery, Rush University Medical of 6 months of conservative management prior to surgical
Center, Orthopedic Building, 1611 W. Harrison St., 2nd intervention [2–4]. Initial conservative treatment for most
Floor, Chicago, IL 60612, USA patients with an acute disc herniation is usually physical
2
The International Spine Research and Innovation Initiative, therapy, non-steroidal anti-inflammatory medications, glu-
Rush University Medical Center, Chicago, IL, USA cocorticoids (either oral or injected), and activity modifica-
3
Department of Orthopaedic Surgery, Cedars-Sinai Medical tion. The duration of recommended conservative care varies,
Center, Los Angeles, CA, USA ranging from 3 to 12 months or longer, with outcomes often
4
Tkachev Clinic, Volgograd, Russia similar between durations [2, 5–7]. Studies have suggested

13
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that though short-term outcomes may favour surgical inter-
vention, longer-term outcomes are less convincing [8–10].
Following an acute injury, it is the normal physiologic
response of the body to initiate an inflammatory process
as a means to begin healing. An acute LDH is no excep-
tion. When the nucleus pulposus breaks its barrier and pro-
trudes through the annulus fibrosis, it sets off a cascade of
cellular events that trigger the release of pro-inflammatory
cytokines that have a central role in promoting matrix degra-
dation, immune cell recruitment, and angiogenesis. The ulti-
mate result of such a process is resorption of the herniated
intervertebral disc tissue [11]. Paradoxically, however, anti-
inflammatory agents, such as NSAIDs and glucocorticoid
compounds, whether systemic or injected, are often first-
line modalities. Blunting the natural healing response of the
body with such anti-inflammatory agents could potentially
increase the duration of LDH [12]. Despite clinical guide-
lines, anti-inflammatory agents carry multiple side effects,
often limiting their use. Along with having significant renal,
gastrointestinal, and cardiovascular adverse effects [13],
the effectiveness of such treatment modalities has not been
firmly established [14]. Additionally, the use of NSAIDs
may be associated with increased costs when paired with
steroid injections [13].
The concept of inflammation-preservation in the treat-
ment of acute LDH has yet to be explored. Therefore,
the authors aimed to examine the outcomes of a uniform
“inflammation-preserving” treatment protocol in acute LDH
patients whereby no NSAIDs or steroids were used for treat-
ment in an effort to assess if the herniated disc would resorb
and at what rate. To address this aim, we performed a one-
year prospective study with multiple sequential magnetic
resonance imaging (MRI) of the lumbar spine to docu-
ment the disc integrity and resorption rates, and in tandem
assess pain profiles in patients undergoing such treatment.
We hypothesized that all patients would demonstrate disc
resorption, both symptomatically and image-based, within
one year.
Methods
Following institutional review board approval, patients with
an acute LDH were prospectively enrolled in the study at a
single institution between 2017 and 19. Patients between
20–70 years of age with new magnetic resonance findings
(MRI) findings of an acute LDH and associated radiculitis
were included. Patients with underlying cognitive impair-
ment, mental disorders, or decompensated somatic disease,
those who had undergone previous lumbar surgery, those
receiving anti-inflammatory medications, and pregnant
women were excluded from the study. Acute LDH was
defined as a new disc herniation occurring in the lumbar
13
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European Spine Journal
spine within 3 weeks as documented on MRI and correlating
with an acute radiation of symptoms into one or both legs.
Treatment protocol
Upon initial evaluation, patient-specific data and visual
analogue scale (VAS) scores were collected. Treatment was
divided into separate courses of treatment, and the number
of treatment courses was dependent on symptom duration
and imaging results. A single course of treatment consisted
of titrated doses of gabapentin, 12 consecutive acupuncture
sessions, and instructions to avoid any anti-inflammatory
medications, oral glucocorticoids, or corticosteroid injec-
tions. Patients were also instructed that they should not
participate in physiotherapy, exercise therapy, and sports. If
these criteria were not adhered to, the patient was excluded.
Each treatment course lasted approximately 3 months, until
all 12 acupuncture sessions were completed. The doses of
gabapentin were adjusted based on the level of leg pain via
VAS scores at week 3 and 8. The initial dosage of gabapentin
was 300 mg at bedtime, and then, the dose was titrated with
a daily increase of no more than 900 mg (with monitoring
of side effects) until the level of pain in the leg was reduced
to a tolerable 3–5 points. Dose adjustments were made every
3 and 8 weeks. The patient also had the opportunity to make
a phone call to the clinic in case of increased pain or side
effects. The acupuncture sessions occurred about once a
week and consisted of 10–20 needles applied for 20 min to
various pressure points, including Jia ji points, non-meridian
Ashi points, and standard classic points.
Following the initial treatment course, a second MRI was
obtained (approximately 3 months between each imaging
session), which stratified patients to dictate further manage-
ment (Fig. 1). If symptoms resolved and the MRI demon-
strated resorption, the treatment was ceased. Herniated tis-
sue reduced by 40% or more and the symptoms (i.e. leg pain)
improvement by greater than or equal to 70% constituted
“complete resorption”. Patients with persistent leg pain, or
MRI findings of an LDH, received a second course of treat-
ment that identically consisted of 12 acupuncture sessions
and titrated doses of gabapentin. After each course of treat-
ment, patients were re-evaluated for resolution of leg pain
and disc 40% disc resorption.
Recovery groups
The patients were divided into 4 groups based on the speed
of recovery. In the fast recovery group, symptoms (i.e.
leg pain) resolved after the first course of treatment. The
patients’ symptoms in the medium recovery group resolved
after the second course of treatment. The slow recov-
ery group’s symptoms resolved after the third treatment
course, and the prolonged recovery group patients required
European Spine Journal
Fig. 1  Study flow chart
treatment through the fourth course of treatment. To clarify,
an initial MRI following the initial treatment session was
performed of all patients. If symptoms or LDH persisted fol-
lowing each round of treatment sessions, subsequent MRIs
were obtained. If symptoms resolved, the treatment ceased.
Magnetic resonance imaging (MRI) measurement
All patients presenting with an acute LDH underwent MRI
within 3 weeks of initial presentation. MRI imaging was
generated from Siemens Symphony 1.5 T (Munich, Ger-
many) or GE Signa HDxt 1.5 T (Chicago, IL) systems.
The maximum area of each disc herniation was measured
via Horos software (Geneva, Switzerland) on sagittal
T2-weighted MRI sequences, tracing from the posterior edge
of adjacent vertebrae in accordance with measurements and
definitions set forth by the North American Spine Society
(NASS), American Society for Spine Radiology (ASSR),
and the American Society of Neuroradiology (ASNR) task
force [15]. All measurements were performed by a neu-
rologist with extensive radiographic experience. Reliability
assessments were performed of the measurements and found
to be of good to excellent reproducibility. While no accu-
racy studies of the Horos system have been published, the
Horos system is similar to the Osirix dicom viewer which
has a reported accuracy of approximately 0.1 mm for sagittal
measurements. As such, the authors of this study concluded
that the accuracy of the Horos system was likely similar to
the aforementioned viewer [16].
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Statistical analyses
All data were captured and recorded unto a spreadsheet.
Descriptive analyses were conducted with SPSS vr. 21
(IBM, Chicago, Illinois). Mean, standard deviation, and
range values were noted of relevant data points. Statistical
analyses were performed to assess significant differences in
count data using a combination of Fisher’s exact and χ2 tests
where applicable, depending on sample size. Continuous
variables are indicated with means, standard deviations (SD;
denoted as mean ± SD), and ranges. For normally distributed
data as assessed by the Shapiro–Wilk test, one-way analy-
sis of variance (ANOVA) and Tukey post hoc tests were
performed. Spearman’s correlations were utilized to assess
potential relationships between initial size of herniation
and other continuous variables (e.g. VAS-Leg, gabapentin
requirements, etc.). Group analyses were based on collected
data only, with no imputation of missing values. Paired t
tests were used to assess the size of the LDH at different time
points. Kaplan–Meier analyses were performed to denote
time to disc resorption (days) in relation to patients with
more than 25%, 50%, and 75% disc resorption. The threshold
for statistical significance was established at p < 0.05.
Results
Overall, 90 patients (n = 46 female, n = 44 male) were
included in the study, with a mean age of 47.9 years
(Table 1). There was notable variation in the treatment
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 European Spine Journal

Table 1  Baseline demographics and subject characteristics Improvement in leg pain

Mean/N SD/%
Although patients in the fast recovery group appeared to
Overall Total 90 have less severe leg pain at baseline, post hoc analyses dem-
Demographics onstrated no difference in baseline leg pain. Leg pain was
Age 48.6 12.1 reduced by at least 70% in all patients (p = 0.036; Table 2).
Sex Gabapentin dosing was titrated to resolve leg pain in each
Female 46 (51.1) group. The mean dose for all groups was 4.52 IU per day in
Male 44 (48.9) the first 12 weeks (Tables 3 and 4). Following the second
BMI 25.1 4.4 clinical visit and first follow-up MRI, the dose required to
Smoking improve symptomatic radiculopathy was 0.98 IU per day.
Yes 15 (16.7) By the time of the third follow-up MRI (fourth MRI), the
No 75 (83.3) mean gabapentin utilization was 0.03 IU per day per patient
Clinical history* (Fig. 4).
Previous history of sciatica
Yes 1 (1.1)
No 89 (98.9) Discussion
Hx of NSAIDs for sciatica
Yes 0 (0.0) Spontaneous regression of the intervertebral disc was first
No 90 (100.0) documented by Key [17] in 1945. Forty-one years later, Tep-
Hx = history; NSAIDs = non-steroidal anti-inflammatory drugs lick and Haskin [18] were the first to observe disc regression
on imaging. Since then, many studies have demonstrated
the spontaneous ability of the intervertebral disc to regress
duration and number of MRIs performed. Nineteen patients without necessitating surgery while improving clinical
demonstrated clinical improvement and resolution of symptoms [19–23]. A major mechanism that has been impli-
the LDH on follow-up MRI after the first course of treat- cated by which this process is thought to occur is through an
ment (fast recovery group). Similarly, 44 patients achieved inflammatory response mounted by the body. With that held
improvement as demonstrated on the follow-up MRI after belief, the present study prospectively evaluated 90 patients
the second course of treatment (medium recovery group). with MRI-proven acute LDH and associated leg pain that
Twenty-one patients required treatment through the third underwent conservative management without the use of the
course of treatment (slow recovery group), and six patients traditional therapeutic approach as mandated by guidelines
required four courses of treatment for the fourth follow- consisting of NSAIDs or steroids. Our findings showed no
up MRI to demonstrate disc resorption of at least 40% association between LDH size and recovery time. Interest-
(prolonged recovery group). The resorption pattern in the ingly, those who recovered most quickly required a lower
four different resorption groups is illustrated in Fig. 2. All initial doses of gabapentin compared to their slow and pro-
patients demonstrated resorption within one year of starting longed counterparts. All patients obtained complete relief in
the study and no patients required surgical intervention. leg pain, avoiding surgical intervention, and demonstrated
disc resorption within one year of starting treatment.

Size of herniation Mechanism of disc resorption

There was no significant difference between recovery groups
in regard to baseline herniation size (Table 2). Comparing
baseline MRI with the first follow-up MRI at 12 weeks, the
fast recovery group had the mean size of their herniation
reduced to 49.2 ­mm2. At this MRI, the size of disc her-
niation demonstrated no significant change in the medium,
slow, and prolonged recovery groups. Figure 3 highlights the
time to disc resorption. Interestingly, initial size of hernia-
tion was weakly correlated with VAS-Leg at presentation
(r = 0.24, p = 0.02). Moreover, there was a moderate correla-
tion between initial size of herniation and initial gabapentin
requirements (r = 0.42, p < 0.001).
In an aim to symptomatically address the pro-inflamma-
tory and pain-producing contents of the intervertebral disc,
published guidelines have recommended initial conserva-
tive management to include anti-inflammatory medications
and a combination of oral and injected steroid medications
[2, 24, 25]. Though these interventions are often success-
ful at treating symptoms, their effect on the inflammatory
cascade and the implications that it could have on the heal-
ing process is often overlooked. Moreover, tissue stress
during an acute lumbar disc herniation triggers a response
resulting in the recruitment of leukocyte and plasma pro-
teins in an aim to achieve homeostasis and begin healing.

13

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European Spine Journal

Fig. 2  Sagittal MRIs of patients

in the A fast, B medium, C
slow, and D prolonged recovery
groups

Table 2  The number of patients in each recovery group and their related size of herniation and leg pain at baseline based on a visual analogue
scale
Groups
Overall Fast recovery Medium recovery Slow recovery Prolonged recov- p value Post hoc Tukey
(n = 90) mean (n = 19) mean (n = 44) mean (n = 21) mean ery (n = 6) mean
(SD) (SD) (SD) (SD) (SD)

Number of follow up – 1 2 3 4 –
Clinic Visits (with
MRI)
Mean size (± SD) in 119.54 (54.34) 120.74 (54.90) 105.46 (40.90) 134.80 (58.69) 165.51 (91.02) 0.135 –
­mm2 of herniation at
baseline
Mean (± SD) leg pain 6.12 (1.13) 5.89 (0.99) 5.93 (1.19) 6.43 (0.98) 7.17 (0.98) 0.036 –
at baseline

For post hoc Tukey analysis, results were reported with p values if determined to be statistically significant. If there were no significant differ-
ences found on post hoc Tukey analysis, a (–) was denoted

13

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 European Spine Journal

Fig. 3  Kaplan–Meier plot of the

time to disc resorption

Table 3  The mean number of daily units of gabapentin in the different recovery groups
Daily IU of gabapentin
Groups Fast recovery Medium recovery Slow recovery Prolonged recovery p value Post hoc Tukey
(n = 19) Mean (SD) (n = 44) Mean (SD) (n = 21) Mean (SD) (n = 6) Mean (SD)

Treatment interval 1 4.31 (2.08) 4.07 (1.80) 5.10 (2.00) 6.50 (1.22) 0.173 Group 2 < group
4 (p = 0.02)
Treatment interval 2 0.97 (1.67) 1.71 (2.02) 1.50 (1.64) 0.523 –
Treatment interval 3 0.00 (0.00) 0.50 (1.22) 0.231 –
Treatment interval 4 0.00 (0.00) –

For post hoc Tukey analysis, results were reported with p values if determined to be statistically significant. If there were no significant differ-
ences found on post hoc Tukey analysis, a (–) was denoted

Table 4  Summary of treatment Visit #1 Visit #2 Visit #3

characteristics
Mean (n = 90) SD Mean (n = 71) SD Mean (n = 27) SD p value

Number of 11.96 0.42 11.94 0.52 0.78 0.74 < 0.001

acupuncture
treatments
Gabapentin 1356 591 294 501 9 93 < 0.001
adminis-
tered (in
mg)
VAS-Leg 6.12 1.13 1.00 1.61 0.00 0.00 < 0.001

Resolution of the inflammatory response is mediated by a
macrophage response and involves a switch in mediators
from prostaglandins to lipoxins, a natural anti-inflamma-
tory [26, 27]. Other lipid mediators, such as resolvins, pro-
tectins, and transforming growth factor-β, are also impli-
cated in the tissue response and initiation of repair [28].
Previous studies addressing disc resorption
Case reports, retrospective cohort analyses, and meta-anal-
yses have highlighted the potential for spontaneous LDH
resorption [29–32]. In a large meta-analysis by Zhong et al.
[31], the incidence of spontaneous resorption of lumbar disc
herniation was examined in 11 studies spanning a total of

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European Spine Journal
Fig. 4  Kaplan–Meier plot of the time length from baseline to full leg pain recovery
587 patients with a LDH. The therapy modalities used in all
of the studies examined were not clearly stated but it was a
combination of analgesics, NSAIDs, steroids, and conserva-
tive treatment. Of the 587 patients included in the meta-
analysis, 380 experienced disc resorption, showing 66.7%
resorption rate. In contrast, 100% of the 90 patients in our
study experienced complete disc resorption while avoid-
ing any anti-inflammatory medications. In a retrospective
study of 9 patients, complete disc resorption was found at a
mean of 8.7 months with clinical improvement at a mean of
5.7 weeks. All patients demonstrated complete disc resorp-
tion while being treated with analgesics and NSAIDs [29].
Compared to the cohort in our study, the average time to
complete disc resorption was 4.4 months and we avoided
any anti-inflammatory medications. The present study more
uniquely evaluated relief in leg pain and MRI-proven resolu-
tion in disc herniation size.
Size of disc herniation at initial and final MRI was
related to symptomatic relief and recovery time. Smaller
disc herniations correlated with a lower VAS-Leg score at
presentation, albeit weakly correlated (r = 0.24), required a
smaller dose of gabapentin. Biologically, smaller herniations
provoke less inflammation and induce less pressure on tra-
versing and exiting nerve roots, given the same location of
the herniation [33]. The smallest noted disc herniation had
an area of 43 ­mm2, whereas the largest herniation meas-
ured 273 m­ m2, requiring a longer duration for macrophage-
driven resorption of disc material including capillarization
and inflammatory resorption [33]. The findings of the pre-
sent study corroborate with those from a previous study by
Fagerlund et al. [34] which evaluated 30 consecutive patients
and highlighted improvement in radicular pain following
diagnosis of an acute LDH. The authors utilized computed
tomography (CT) to evaluate herniation size which has infe-
rior sensitivity and specificity when compared to MRI [35].
Though improvement was noted both clinically and on CT,
traction therapy was the only noted conservative treatment
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modality, and the authors did not utilize medication for
symptomatic relief.
Acupuncture and gabapentin
Acupuncture is a well-accepted technique demonstrating
pain relief [36]. Specifically, systematic reviews have sug-
gested that acupuncture may have increasing indications as
an adjunct treatment in low back pain [37–39]. Acupuncture
similarly may improve acute radiculopathy and reduce anti-
inflammatory intake [40, 41]. In the present study, acupunc-
ture was used following established techniques as an adjunct
to Gabapentin and there were no side effects noted.
Gabapentin, originally developed for the treatment of
epilepsy, has numerous side effects including dizziness,
somnolence, central hypoventilation, myopathy, and sui-
cidal ideation [42]. Such side effects are often avoided with
appropriate titration of dosing and has become increasingly
prescribed in the treatment of neurologic and extremity pain
[43]. However, the role of gabaergic drugs, specifically pre-
gabalin, has been more recently re-evaluated and may play
less of a role in treatment of radicular pain [44].
NSAIDs and steroids
NSAIDs have often demonstrated a lack of efficacy in
a recent Cochrane review and may be associated with
increased costs though their use continues in the early treat-
ment of symptomatic LDH [14, 45]. Among other nega-
tive side effects, nearly half of patients consuming anti-
inflammatory medications may suffer from gastric erosions,
further limiting their use [35, 46]. Similarly, a randomized
clinical trial of 269 patients demonstrated no significant pain
reduction with oral steroid administration [47]. In the pre-
sent study, as suggested in Fig. 5, gabapentin dosing was
related to recovery time. The fast recovery group had less
total consumption of gabapentin than the prolonged recovery
13

Fig. 5  The size of the disc herniation in m 2
­ m in the four recovery
groups at the time of MRI capture
group and those with a larger disc herniation. Our study is
in accordance with the study of Wang et al. [48] who in
a systematic review of 38 studies evaluated the incidence
of resorption after non-surgical treatment of symptomatic
LDH. The authors found an overall resorption rate of 63%
among non-surgically treated disc patients; however, they
did not give a clear definition of resorption. They stated that
their findings provide clinical decision makers with quantita-
tive evidence of resorption. The authors further suggested
a follow-up timeline with time points 4 and 10.5 months
after onset when deciding whether to perform surgery for
LDH [48].
Strengths and limitations
There are several limitations in the present study. It is not
commonplace to perform repeat MRI unless there is fur-
ther neurologic compromise or lack of improvement with
extended periods of conservative care. Following initial
diagnosis, the decision to continue or terminate treatment is
often solely based upon symptomatic relief. However, the
institution had readily available access to three nearby MRI
centres, providing unique data regarding disc herniation size
and the natural history of disc resorption with MRI measure-
ments made over a 12-month period. As such, “multiple”
MRIs at different time points were taken of patients within
a one-year time frame to document the disc integrity. Sec-
ondly, the natural history of an acute LDH is often argued,
with proponents suggesting improvement regardless of inter-
vention. While NSAIDs, in conjunction with steroid agents,
pose an increased cost and side effect profile, alternative
lower-risk modalities such as acupuncture and gabapentin
may pose useful alternatives despite any potential placebo
effect. While the lack of a control group introduces inherent
biases that are otherwise avoided, the present prospective
13
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European Spine Journal
study is one of the largest series to assess the natural history
of disc resorption via multiple MRIs within a one-year time
span and the first to systematically assess patients under-
going such inflammation-preserving treatment. Moreover,
while we showed resorption within a year, it should be noted
that patients who have pain at LDH for more than 3 months
have a worse outcome than patients who are operated on
beforehand. As such, even if conservative therapy has a high
value, pain chronification should not be underestimated [48].
Conclusion
It has become common practice to prescribe anti-inflamma-
tory agents, such as NSAIDs and glucocorticoids, for the
treatment of acute LDH despite inconclusive evidence for
the efficacy of such management. This is the first study, to
the authors knowledge, to not only note that inflammation-
preserving treatment (i.e. no NSAIDs, steroids) to be safe
and effective for all patients with an acute LDH, but to report
on outcomes with this protocol. All patients (100%) experi-
enced improvement in VAS-Leg scores with MRI-verified
resorption of disc material at a mean of 4.4. months follow-
ing initial (pre-treatment) MRI. Our study raises awareness
on the physiology behind natural disc resorption and the
alternative yet beneficial treatment for LDH. Furthermore,
our work and concept directly challenge the current dogma
of how patients with LDH should or can be managed, pro-
viding evidence that alternative methods are available that
are safe and effective, and may potentially be superior than
long-held traditional guidelines. Future randomized control
trials are needed to control for various biases and better
understand the natural history of acute LDH. If our findings
remain true in future investigations, our proposed treatment
approach may alter the management of patients with symp-
tomatic disc herniations that can have tremendous impact
upon patients, healthcare professionals, insurance providers,
and other stakeholders worldwide.
Declarations
Conflict of interest The authors have no financial or competing inter-
ests to disclose in relation to this work.
Ethics approval Local scientific committee, IRB #00005839 IORG
0004900 (OHRP), Protocol N 2125-2019.
References
1. Murray CJ, Lopez AD (2013) Measuring the global burden of
disease. N Engl J Med 369:448–457
European Spine Journal
2. Kreiner DS, Hwang SW, Easa JE et al (2014) An evidence-based
clinical guideline for the diagnosis and treatment of lumbar disc
herniation with radiculopathy. Spine J 14:180–191
3. Sugimoto MA, Sousa LP, Pinho V, Perretti M, Teixeira MM
(2016) Resolution of inflammation: what controls its onset? Front
Immunol 7:160
4. Albert HB, Manniche C (2012) The efficacy of systematic active
conservative treatment for patients with severe sciatica: a single-
blind, randomized, clinical, controlled trial. Spine (Phila Pa 1976)
37:531–542
5. Movassaghi K, Basques BA, Louie PK et al (2019) The duration
of symptoms does not impact clinical outcomes following lumbar
decompression surgery. Spine (Phila Pa 1976) 44:305–308
6. Sayari AJ, Harada GK, Basques BA et al (2021) Duration of
symptoms does not affect clinical outcome after lumbar arthro-
desis. Clin Spine Surg 34:E72-e79
7. Majid K, Fischgrund JS (2008) Degenerative lumbar spon-
dylolisthesis: trends in management. J Am Acad Orthop Surg
16:208–215
8. Lurie JD, Tosteson TD, Tosteson AN et al (2014) Surgical ver-
sus nonoperative treatment for lumbar disc herniation: eight-year
results for the spine patient outcomes research trial. Spine (Phila
Pa 1976) 39:3–16
9. Lequin MB, Verbaan D, Jacobs WC et al (2013) Surgery versus
prolonged conservative treatment for sciatica: 5-year results of a
randomised controlled trial. BMJ Open 3(5):e002534
10. Gugliotta M, da Costa BR, Dabis E et al (2016) Surgical versus
conservative treatment for lumbar disc herniation: a prospective
cohort study. BMJ Open 6:e012938
11. Cuéllar JM, Borges PM, Cuéllar VG, Yoo A, Scuderi GJ, Yeomans
DC (2013) Cytokine expression in the epidural space: a model
of noncompressive disc herniation-induced inflammation. Spine
(Phila Pa 1976) 38:17–23
12. Minamide A, Tamaki T, Hashizume H, Yoshida M, Kawakami
M, Hayashi N (1998) Effects of steroid and lipopolysaccharide
on spontaneous resorption of herniated intervertebral discs.
An experimental study in the rabbit. Spine (Phila Pa 1976)
23:870–876
13. Henry DA (1988) Side-effects of non-steroidal anti-inflammatory
drugs. Baillieres Clin Rheumatol 2:425–454
14. Rasmussen-Barr E, Held U, Grooten WJ, et al. (2016) Non-ste-
roidal anti-inflammatory drugs for sciatica. Cochrane Database
Syst Rev 10: Cd012382.
15. Fardon DF, Williams AL, Dohring EJ, Murtagh FR, Gabriel Roth-
man SL, Sze GK (2014) Lumbar disc nomenclature: version 2.0:
recommendations of the combined task forces of the North Ameri-
can spine society, the American society of spine radiology and the
American society of neuroradiology. Spine J 14:2525–2545
16. Kim G, Jung HJ, Lee HJ, Lee JS, Koo S, Chang SH (2012) Accu-
racy and reliability of length measurements on three-dimensional
computed tomography using open-source OsiriX software. J Digit
Imaging 25:486–491
17. Key JA (1945) Intervertebral disk lesions are the most com-
mon cause of low back pain with or without sciatica. Ann Surg
121:534–539
18. Teplick JG, Haskin ME (1985) Spontaneous regression of herni-
ated nucleus pulposus. AJR Am J Roentgenol 145:371–375
19. Borota L, Jonasson P, Agolli A (2008) Spontaneous resorption of
intradural lumbar disc fragments. Spine J 8:397–403
20. Bozzao A, Gallucci M, Masciocchi C, Aprile I, Barile A, Passari-
ello R (1992) Lumbar disk herniation: MR imaging assessment
of natural history in patients treated without surgery. Radiology
185:135–141
21. Reyentovich A, Abdu WA (2002) Multiple independent, sequen-
tial, and spontaneously resolving lumbar intervertebral disc her-
niations: a case report. Spine (Phila Pa 1976) 27:549–553
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
22. Slavin KV, Raja A, Thornton J, Wagner FC Jr (2001) Spontane-
ous regression of a large lumbar disc herniation: report of an
illustrative case. Surg Neurol 56:333–336
23. Yamashita K, Hiroshima K, Kurata A (1994) Gadolinium-
DTPA–enhanced magnetic resonance imaging of a sequestered
lumbar intervertebral disc and its correlation with pathologic
findings. Spine (Phila Pa 1976) 19:479–482
24. Wong JJ, Côté P, Sutton DA et al (2017) Clinical practice
guidelines for the noninvasive management of low back pain:
a systematic review by the Ontario protocol for traffic injury
management (OPTIMa) collaboration. Eur J Pain 21:201–216
25. O’Donnell JL, O’Donnell AL (1996) Prostaglandin E2 con-
tent in herniated lumbar disc disease. Spine (Phila Pa 1976)
21:1653–1655
26. Serhan CN, Savill J (2005) Resolution of inflammation: the
beginning programs the end. Nat Immunol 6:1191–1197
27. Medzhitov R (2008) Origin and physiological roles of inflam-
mation. Nature 454:428–435
28. Serhan CN (2007) Resolution phase of inflammation: novel
endogenous anti-inflammatory and proresolving lipid media-
tors and pathways. Annu Rev Immunol 25:101–137
29. Elkholy AR, Farid AM, Shamhoot EA (2019) Spontaneous
resorption of herniated lumbar disk: observational retrospec-
tive study in 9 patients. World Neurosurg 124:e453–e459
30. Benson RT, Tavares SP, Robertson SC, Sharp R, Marshall RW
(2010) Conservatively treated massive prolapsed discs: a 7-year
follow-up. Ann R Coll Surg Engl 92:147–153
31. Zhong M, Liu JT, Jiang H et al (2017) Incidence of spontane-
ous resorption of lumbar disc herniation: a meta-analysis. Pain
Physician 20:e45–e52
32. Sakai T, Tsuji T, Asazuma T, Yato Y, Matsubara O, Nemoto K
(2007) Spontaneous resorption in recurrent intradural lumbar
disc herniation. Case report J Neurosurg Spine 6:574–578
33. Yang H, Liu H, Li Z et al (2015) Low back pain associated with
lumbar disc herniation: role of moderately degenerative disc and
annulus fibrous tears. Int J Clin Exp Med 8:1634–1644
34. Fagerlund MK, Thelander U, Friberg S (1990) Size of lumbar
disc hernias measured using computed tomography and related
to sciatic symptoms. Acta Radiol 31:555–558
35. Forristall RM, Marsh HO, Pay NT (1988) Magnetic resonance
imaging and contrast CT of the lumbar spine. Comparison of
diagnostic methods and correlation with surgical findings. Spine
(Phila Pa 1976) 13:1049–1054
36. Paley CA, Johnson MI (2019) Acupuncture for the relief of
chronic pain: a synthesis of systematic reviews. Medicina (Kau-
nas) 56(1):6
37. Foster NE, Anema JR, Cherkin D et al (2018) Prevention and
treatment of low back pain: evidence, challenges, and promising
directions. Lancet 391:2368–2383
38. Liu L, Skinner M, McDonough S, Mabire L, Baxter GD (2015)
Acupuncture for low back pain: an overview of systematic
reviews. Evid Based Complement Alternat Med 2015:328196
39. Bronfort G, Haas M, Evans RL, Bouter LM (2004) Efficacy of
spinal manipulation and mobilization for low back pain and
neck pain: a systematic review and best evidence synthesis.
Spine J 4:335–356
40. Xiang A, Xu M, Liang Y, Wei J, Liu S (2017) Immediate relief
of herniated lumbar disc-related sciatica by ankle acupuncture:
a study protocol for a randomized controlled clinical trial. Medi-
cine (Baltimore) 96:e9191
41. Tang S, Mo Z, Zhang R (2018) Acupuncture for lumbar disc
herniation: a systematic review and meta-analysis. Acupunct
Med 36:62–70
42. Moore J, Gaines C (2019) Gabapentin for chronic neuropathic
pain in adults. Br J Community Nurs 24:608–609
13
 European Spine Journal

43. Quintero GC (2017) Review about gabapentin misuse, interac-
tions, contraindications and side effects. J Exp Pharmacol 9:13–21
44. Mathieson S, Maher CG, McLachlan AJ et al (2017) Trial
of pregabalin for acute and chronic sciatica. N Engl J Med
376:1111–1120
45. Pinto RZ, Maher CG, Ferreira ML et al (2012) Drugs for relief of
pain in patients with sciatica: systematic review and meta-analy-
sis. Bmj 344:e497
46. Laine L (1996) Nonsteroidal anti-inflammatory drug gastropathy.
Gastrointest Endosc Clin N Am 6:489–504
47. Goldberg H, Firtch W, Tyburski M et al (2015) Oral steroids for
acute radiculopathy due to a herniated lumbar disk: a randomized
clinical trial. Jama 313:1915–1923
48. Wang Y, Dai G, Jiang L, Liao S (2020) The incidence of regres-
sion after the non-surgical treatment of symptomatic lumbar disc
herniation: a systematic review and meta-analysis. BMC Muscu-
loskelet Disord 21:530
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