Joint Bone Spine 2002 ; 69 : 155-60

© 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved

S1297319X02003858/REV REVIEW

The natural history of lumbar disc herniation

and radiculopathy

Michel Benoist*
113, avenue Victor-Hugo, 75116 Paris, France

(Submitted for publication March 23, 2001; accepted in revised form June 26, 2001)

Summary – The majority of patients suffering from a radiculopathy caused by a herniated nucleus
pulposus (HNP) heal spontaneously without surgery or chemonucleolysis. The clinical course of the
radiculopathy varies as well as the efficacy of conservative treatment. In some patients the symptoms
decline after a week or two; in others the pain may continue for many months or years. Despite an abundant
literature there is still a controversy concerning the treatment of radiculopathies related to ruptured lumbar
intervertebral discs. Obviously knowledge of the natural history of discal herniation, and of the mechanisms
leading to the changes of the extruded discal tissue, would be of great help in planning the therapeutic
procedure. The purpose of this article is to review the reliable data concerning the clinical and pathomor-
phological evolution and the biological mechanisms associated with the morphologic changes of discal
herniation. Joint Bone Spine 2002 ; 69 : 155-60. © 2002 Éditions scientifiques et médicales Elsevier SAS
inflammatory cytokines / lumbar disc herniation / metalloproteinases / natural evolution

CLINICAL EVOLUTION group of 126 patients with uncertain indication for

Very few studies concern the natural evolution of the
clinical symptoms, as most patients undergo some kind
of medical treatments. Hakelius [1] reviewed the course
of the acute sciatica syndrome with conservative treat-
ment in 38 non-operated patients with a discal hernia-
tion on myelography. Treatment only consisted of bed
rest and bracing. Appreciation of evolution of symp-
toms was made according to the patient’s subjective
assessment, and to the period of official sick registra-
tion. As shown in table I, 35 out of the 38 patients
(88%) were free of symptoms after 6 months but 11 of
them were still registered as sick. Weber [2] analyzed a
* Correspondence and reprints.
surgical treatment, who had their therapy decided by
randomization which permitted comparison between
the results of surgical and conservative treatment. Sixty-
six patients were randomized in the conservative group.
They all had a positive myelography and were treated
by rest, bracing and paracetamol. Tables II and III show
the assessments of results in the conservatively treated
patients after 1 and 4 years. After 1 year 60% (n = 40)
of patients had good or fair results, 17 had been oper-
ated on and nine were still incapacitated by back pain
and sciatica. After 4 years, five of the 49 non-operated
patients remaining in the original group were still suf-
fering from sciatica. At that follow-up time the differ-
ence in the randomized surgical group was no longer
significant. Only minor changes took place during the
last 6 years of observation. In a multicenter prospective
156 M. Benoist
Table I. Evolution of 38 cases of sciatica in non-operated patients
with positive myelography (from [1]).
10–30 days 2 months 3 months 6 months
Free of symptoms 58% 60% 75% 88%
study Weber et al. [3] analyzed 208 patients with
obvious symptoms and signs of lumbar radiculopathy
probably due to a disc herniation. All patients were
examined within 14 days of onset. A concomitant
double-blind investigation of the effect of the nonste-
roidal anti-inflammatory drug piroxicam was per-
formed. Results were assessed at 2 and 4 weeks using a
visual analogue scale and Roland’s functional tests. In
addition questionnaires were sent at 3 and 12 months.
During the first month, significant decrease of pain
(V.A.S. mean score 54 to [19] was observed in 70% of
the patients; 60% were back to work. After 1 year 30%
still complained of back pain and/or sciatica and 20%
had not resumed work. Four patients had been oper-
ated on. The piroxicam-treated group had the same
results as the placebo control group.
In a randomised double-blind study Fraser [4] ana-
lyzed 60 patients with a discal herniation documented
by myelography. Thirty underwent a chymopapain
chemonucleolysis and 30 received a placebo. At 6 weeks
37% of the placebo group had a good outcome, which
increased to almost 60% at 6 months. By 2 years 40%
of patients of the placebo group had been operated [5].
In spite of the paucity of information, results of these
studies and personal experience suggest that natural
evolution of the clinical symptoms can be summarized
as follows: in the first 2 months there is a marked
decrease of back and leg pain in approximately 60% of
Table II. Assessment at 1 year of 66 patients conservatively treated
with positive myelography (from [2]).
Good and fair 40
Poor and bad 9 respectively in 29% and 8% of the remaining patients.
Operated 17 40 %
Total 66
Table III. Assessment at 4 years of 66 patients conservatively
treated with positive myelography (from [2]).
Good and fair 44
Poor and bad 5 formed with a mean interval of 6 months. Disappear-
Operated 17 33 %
Total 66
patients. At one year 20–30% are still complaining of
back and/or leg pain. Surgery is usually decided within
the first year.
PATHOMORPHOLOGICAL EVOLUTION
In recent years numerous studies have shown that a disc
herniation may decrease in size and even disappear
spontaneously. No report on this subject could be
found before the advent of computed tomography
(CT). In order to evaluate the frequency and time
frame of regression of discal herniation in patients
recovering with a conservative treatment, a computer
literature search was performed. As the clinical course
of a symptomatic lumbar disk herniation is generally
unpredictable it would be very helpful to document the
predictive parameters of regression. The literature data
will be analyzed in a chronological order.
Teplick [6] was the first to report 11 patients in
whom there was unequivocal regression or disappear-
ance of a herniated lumbar disc on follow-up CT study,
with a clinical improvement accompanying the mor-
phologic changes. In 1990, Saal and Saal [7] reported
on 12 patients treated non-operatively with a good
outcome. After a successful treatment the patients
underwent follow-up MRI scans that revealed that
46% had 75–100% resorption, 36% had 50–75%
decrease in size, and 11% had 0–50% diminution. The
mean interval between the two scans was 25 months.
Total resorption was more frequently observed in the
largest herniations. Clinical improvement and mor-
phologic changes did not necessarily follow the same
time course. In 1992, several authors reported similar
findings. Bozzao et al. [8] reported on a series of non-
operated 69 patients with discal herniations of various
locations and sizes proven at MRI imaging. The mean
interval between the two scans was 11 months. Reduc-
tion of more than 70% was observed in 48% of patients,
30–70% in 15%. No change or increase was observed
There was no significant correlation between the loca-
tion of the herniations and the reduction of the hernia-
tion. In contrast, the high rate of resorption (over 70%)
was observed in the large and medium herniations.
Delauche et al. [9] have treated successfully and conser-
vatively 21 patients with a lumbar discal herniation
proven by CT scanning. A subsequent CT was per-
ance or major decrease was observed in ten patients,
moderate diminution in four, and no change in the
 Lumbar disc herniation and radiculopathy
Table IV. Evolution of the discal herniation in 48 conservatively
treated patients. Interval between the two scans: 1 to 40 months
(from [10]).
No of cases
Group 1 (Decrease less than 25%) 9 Disappearance (n = 10)
Group 2 (Decrease from 50 to 75%) 8 Marked decrease (n = 25)
Group 3 (Decrease more than 75%) 31
48
remaining patients in spite of the disappearance of the
clinical symptoms. Maigne et al. [10] have followed the
course of 48 patients who had a second scan 1 to 40
months after the first imaging. A decrease in the size of
75% or more was observed in 64% of patients, with a
diminution from 50–75% in 17%, and from 25–50%
in 19%. Tables IV and V summarize respectively the
comparison CT1 and CT2, and the evolution accord-
ing to the size of the herniation. Only half of the small
herniations decreased by over 75%. Conversely, the
great majority of the large herniations disappeared or
underwent a major shrinkage.
In a prospective study, Bush et al. [11] followed 111
patients successfully with either a discal herniation
(n = 84) or a generalized or focal bulge (n = 27). The
second scan was done 1 year later in all patients treated
conservatively with a satisfactory outcome. Sixty-four
out of 84 herniations were resolved or improved after 1
year. Only seven out of 27 bulging discs showed any
resolution. In 1995, Komori et al. [12] studied retro-
spectively 77 patients with lumbar radiculopathy caused
by a disc herniation. All patients were studied more
than twice by MRI imaging during the conservative
treatment, with a mean interval of 150 days. Morpho-
logic changes and their correlation with the clinical
outcome are presented in table VI. Improvement of
clinical findings was usually seen before those observed
on MRI. The further the herniated nucleus pulposus
migrated the more decrease in size could be observed.
Small herniations and protrusions showed little or no
change.
Table V. Decrease of the discal herniations according to their size in
48 conservatively treated patients. Interval between the two scans: 1
to 40 months (from [10]).
Herniations Group 1 Group 2 Group 3
less than 25% 50–75% Over 75%
Small (n = 13) 5 1 7 fragment behind the posterior ligament, the main
Medium (n = 20) 3 5 12
Large (n = 15) 1 1 13
157
Table VI. Correlation between MRI changes and clinical outcomes in
patients conservatively treated. Mean interval between the two scans:
150 days (from [12]).
MRI changes Excellent and good Poor
10 0
25 0
Slight decrease (n = 14) 14 0
No change (n = 28) 13 15
62 ( 80 %) 15 (20 %)
The data provided by the studies previously analyzed
can be summarized as follows: large and migrated her-
niations tend to decrease to a greater extent than pro-
trusions or small contained herniations which have less
tendency to spontaneous regression. Morphologic
changes are usually observable after 6 months and
correspond to a favourable clinical outcome but they
tend to lag behind improvement of leg pain. Finally,
there is a group of patients who become asymptomatic
without any decrease in size of their herniation. This
finding raises the problem of the mechanism of the
radicular pain.
MECHANISMS INVOLVED IN
THE PATHOMORPHOLOGICAL CHANGES
Before the advent of CT scanning and MRI it was
generally thought that clinical improvement of patients
with a positive myelography was related to decrease of
the nerve root inflammation and swelling. Moreover,
retraction of the annulus and its associated herniation
after extreme flexion of the spine, which is the usual
position taken by bed-rest patients, was also hypoth-
esized [13]. The recent imaging findings have demon-
strated that the herniated discal tissue was indeed able
to decrease in size and even disappear, thus releasing the
mechanical pressure on the nerve root. Until recently
little was known about the mechanisms leading to the
decrease of the discal herniation. Teplick [6], who was
the first to report on spontaneous regression of herni-
ated nucleus pulposus (HNP), suggested three theoreti-
cal possibilities: i) Dehydration and shrinkage of the
HNP; ii) regression of the HNP into the annulus via
the tear in the annulus; and iii) fragmentation and
subsequent sequestration at a distance from the annulus
and from the nerve root. In the case of a contained
mechanism may be dehydration but this theoretical
consideration remains speculative. In the case of
158 M. Benoist
extruded or sequestrated fragments exposed in the epi-
dural space, recent studies have demonstrated that
resorption was the mechanism of regression of the
HNP [13-18].
Histologic studies [13, 16] have shown the presence
of a granulation tissue with an abundant neovascular-
ization surrounding the fibrocartilage fragment. Mono-
nuclear cells infiltrate along the margin of the necrotic
and degenerated part of the disc tissue. This granula-
tion tissue was seen in 11 of 16 extruded HNP and
three of five sequestrated HNP in one study [13] and in
30 of 35 sequestrated HNP in another study [16]. The
high vascularity of the granulation tissue explains the
findings of gadolinium-enhanced MRI. The intense
peripheral enhancement of the discal fragment is related
to the accumulation of the contrast material in the
blood vessels of the granulation tissue around the
extruded or sequestrated disc [19]. Gronblad et al. [14]
have studied immunocytochemically the abundant
inflammatory cells present in the granulation tissue.
Using specific monoclonal antibodies, they demon-
strated that macrophages were the predominant cells.
In a histological analysis of many samples from patients
with extrusion or sequestration types, fibroblasts and
endothelial cells were also disclosed, constituting with
the macrophages the granulation tissue. Takahashi et
al. [18] investigated samples from patients with the
protrusion type. The majority of cells were chondro-
cytes. It is interesting to point out that many years ago,
back in 1950, Lindblom [20] had clearly understood
the resorption process. He considered that the cellular
and vascular in-growth was ‘eating’ and destroying the
discal tissue.
The intimate mechanism of the destruction of the
discal tissue has not been fully elucidated. However, it
has been demonstrated that at the site of lumbar disc
herniation, inflammatory cytokines such as Il1, Il6,
TNF alpha, and granulocyte macrophage colony stimu-
lating factor are produced (by macrophages in extru-
sion and sequestration types, and by chondrocytes in
the protrusion type [18]. It has also been shown that
cells of herniated degenerated discs produce matrix
metalloproteinases, nitric oxide and prostaglandin E2.
This production is increased if the cells are stimulated
by Il1 [21]. An increased production of collagenase
(MMP-1) and of antihuman stromelysin (MMP-3)
associated with inflammatory cells in herniated discs, as
well as chondrocytes, has also been demonstrated by
Matsui et al [17]. This suggests a causal correlation of
the proteinases in degradation of the discal tissue. Col-
lagenase and stromelysin have a high specificity for
cartilage matrix and are effective in degrading cartilage
matrix as shown by experimental studies using these
proteinases as chemonucleolytic agents [22]. As previ-
ously mentioned the production of proteolytic enzymes
by activated macrophages can be stimulated by cytok-
ines including Il1 and TNF alpha [18]. Production of
Il1 by the mononuclear cells might be the main starter
of the cycle leading to the production of the cytokines,
which in turn stimulate the production of the protein-
ases. However, the biochemical process is likely to be
more sophisticated. Other cytokines are probably
involved. For example, Haro et al. [15] have demon-
strated the production by the mononuclear cells of the
granulation tissue of monocyte chemotactic protein 1
and macrophage inflammatory protein 1 alpha. Both
cytokines belong to the beta-chemokine family which
further recruit and activate macrophage into the lesion.
Doita et al. [13] have also shown that the cells infiltrat-
ing along the margins of extruded discs express cell
adhesion molecules which regulate immune cells’ migra-
tion and activation. Moreover, basic fibroblast growth
factor which promotes neovascularization is also
expressed on the endothelial cells and chondrocytes of
the granulation tissue. Obviously, the pathophysiology
of the resorption process is extremely complex as well as
the autoregulation of the cytokine network.
Figure 1 presents a hypothetical and rough sketch of
the biological events leading to the discal resorption.
The main instigator which brings the cells into the
lesions and starts the cycle remains hypothetical. Doita
et al [13] have postulated that extrusion of nucleus
pulposus into the epidural space could evoke an autoim-
mune reaction to the antigenic components of the
discal fragment considered as foreign. This theoretical
consideration has already been discussed by a few
authors [23]. It is interesting to point out that Il1 and
TNF alpha produced at the site of disc herniation
increase the production of prostaglandin E2 in the
tissue which may result in direct stimulation of the
nerve root and cause sciatic pain. Recently Aoki et al.
[24] have shown that TNF alpha was the cytokine
directly responsible for nerve root injury. Therapeutic
use of anti-TNF alpha to reduce sciatic pain may inter-
fere with the production cycle of the proteinase respon-
sible for HNP resorption. It can be concluded that
more basic research is needed to clearly understand the
complex biological scenarios leading to discal tissue
resorption and radicular pain.
 Lumbar disc herniation and radiculopathy 159

Figure 1. Hypothesis for discal herniation resorption, radicular injury and pain.

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