This study examined the effectiveness of platelet-rich plasma (PRP) injections for chronic lumbar diskogenic pain. 47 participants with chronic low back pain received either an intradiskal PRP injection or a control injection after provocative diskography. Participants who received PRP reported significantly greater improvements in pain, physical function, and satisfaction over the 8 week period compared to the control group. At the 1 year follow up, those receiving PRP maintained significant improvements in physical function. No serious adverse events were reported. The study provides preliminary evidence that PRP injections may effectively treat chronic low back pain caused by damaged disks. Larger and more standardized studies are still needed.

1. Original Research
Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections:
A Prospective, Double-Blind, Randomized Controlled Study
Q5 Yetsa A. Tuakli-Wosornu, MD, MPH, Alon Terry, MD, Kwadwo Boachie-Adjei, BS, CPH,
Julian R. Harrison, BS, Caitlin K. Gribbin, BA, Elizabeth E. LaSalle, BS,
Joseph T. Nguyen, MPH, Jennifer L. Solomon, MD, Gregory E. Lutz, MD
Abstract
Objective: To determine whether single injections of autologous platelet-rich plasma (PRP) into symptomatic degenerative
intervertebral disks will improve participant-reported pain and function.
Design: Prospective, double-blind, randomized controlled study.
Setting: Outpatient physiatric spine practice.
Participants: Adults with chronic (!6 months), moderate-to-severe lumbar diskogenic pain that was unresponsive to conservative
treatment.
Methods: Participants were randomized to receive intradiskal PRP or contrast agent after provocative diskography. Data on pain,
physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year. Participants in
the control group who did not improve at 8 weeks were offered the option to receive PRP and subsequently followed.
Main Outcome Measures: Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function
domains of the 36-item Short Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire
were used.
Results: Forty-seven participants (29 in the treatment group, 18 in the control group) were analyzed by an independent observer
with a 92% follow-up rate. Over 8 weeks of follow-up, there were statistically significant improvements in participants who
received intradiskal PRP with regards to pain (NRS Best Pain) (P ¼ .02), function (FRI) (P ¼ .03), and patient satisfaction (NASS
Outcome Questionnaire) (P ¼ .01) compared with controls. No adverse events of disk space infection, neurologic injury, or
progressive herniation were reported following the injection of PRP.
Conclusion: Participants who received intradiskal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient
satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI
scores through at least 1 year of follow-up. Although these results are promising, further studies are needed to define the subset
of participants most likely to respond to biologic intradiskal treatment and the ideal cellular characteristics of the intradiskal PRP
injectate.
Introduction
Low back pain (LBP) is a common, often confounding
problem for patients and physicians. In the United States,
at least 80% of adults experience at least 1 episode of LBP
during their lifetime [1]. LBP is the most common cause of
disability among Americans between 45 and 65 years of
age [2]. Furthermore, of all musculoskeletal conditions,
LBP imposes the greatest economic burden on the U.S.
health care system [3]. Although most cases of LBP are
self-limited, approximately 20% recur within 6 months of
the initial episode and a subset of patients experience
chronic symptoms thereafter. For individual patients
and the national health care system, LBP imposes high
physical and financial costs [4,5].
Numerous anatomic structures can cause LBP [6-8].
The intervertebral disk (IVD) accounts for 40% or more
cases of chronic LBP [9]. Noninvasive imaging methods
used to identify spine pathology have limited ability
to determine the exact source of pain [10-13]. Dis-
kography, although controversial, remains a provocative
diagnostic test for pain generated by the IVD [14].
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2. The adult IVD is the largest avascular structure in the
human body. Small branches of the metaphyseal
arteries around the outer annulus comprise its limited
vasculature. IVDs therefore rely on passive diffusion
from adjacent endplate vessels for nutrition [15]. With
limited vascular supply and largely indirect access to
nutrition, the IVD has poor inherent healing potential.
The rationale behind intradiskal injection of platelet-
rich plasma (PRP) is to place a high concentration of
growth factors directly at the site of collagen injury or
degeneration, where they are habitually found in low
concentration. We hypothesize that circulating growth
factors (eg, platelet-derived growth factor, trans-
forming growth factor, insulin-like growth factor, and
vasoendothelial growth factor) and cytokines in PRP will
act as humoral mediators to induce the natural healing
cascade [16-18]. Preclinical, in vitro studies support this
hypothesis. Analysis of PRP-infused human IVD speci-
mens demonstrated cell proliferation and differentia-
tion, as well as up-regulated type II collagen and
proteoglycan synthesis via chondrogenesis [19]. In an
animal model, intradiskal PRP led to restoration of
normal cellular architecture and disk height in an
experimentally injured IVD [20,21].
Readily available and cost-effective compared with
surgical options, a prohealing therapy such as autolo-
gous PRP suits the pathoanatomic cascade that episodic
LBP represents. In comparison with surgical manage-
ment of the internally disrupted IVD, autologous PRP
could be a safer and more cost-effective therapy if
proven to be of benefit.
A major advantage of PRP is its breadth of potential
clinical applications. Unlike an isolated growth factor,
PRP is a mixture of autologous growth factors, cells, and
fibrin readily accessible for use. The injection of fibrin
itself may catalyze sealing of annular fissures [22]. Po-
tential disadvantages of PRP include the relatively small
amount of growth factor delivered (nanogram scale) and
the variance of composition from subject to subject.
Among other considerations, subject cell count and the
specific harvesting system used influence the final con-
stituent factors of the PRP graft. Although PRP has
demonstrated promising results for a variety of muscu-
loskeletal conditions, small sample sizes and lack of
standardization of graft preparation have hampered
research efforts. This study sought to investigate
whether a single intradiskal injection of PRP, delivered
to the symptomatic IVD(s), would confer clinical benefit
for individuals with chronic diskogenic LBP.
Materials and Methods
Study Design
This was a prospective, double-blind, randomized,
controlled study of participants with chronic lumbar
diskogenic pain treated with an intradiskal PRP
injection. The study was approved by the Hospital for
Special Surgery Institutional Review Board and the
Conflict of Interest Committee in Research (Institutional
Review Board #29-025). The study was funded by the
institution’s Physiatry Research & Education Fund. The
PRP preparation kits and centrifuge were donated by
Harvest Technologies Corporation (Plymouth, MA).
Primary Hypothesis
Single injections of autologous PRP into symptomatic
degenerative IVDs will improve participant-reported
pain and function.
Participant Recruitment
One hundred nine participants were assessed for
eligibility at a single academic outpatient spine practice
between May 2009 and November 2013 based on the
general inclusion and exclusion criteria set forward
(Table 1). Fifty-one participants were not enrolled in
the study (26 did not meet inclusion criteria and 25
declined to participate). A total of 58 participants met
the prediskography inclusion criteria and were ran-
domized for inclusion into the study. After diskography,
7 participants were excluded because of either the
presence of a Grade V annular fissure or the lack of
concordant pain at time of injection with contrast.
Three participants failed to maintain inclusion/exclu-
sion criteria after undergoing the procedure, and 1 was
lost to follow-up, yielding a follow-up rate of 92%
(Figure 1).
Study Protocol
Participants with a history of chronic axial LBP who
met inclusion and exclusion criteria were recruited.
Participants were evaluated by 2 interventional spine
and sports medicine physiatrists within the same prac-
tice and enrolled in the study if prediskography inclu-
sion criteria were met. General demographic
information, including age and gender, as well as
baseline outcome scores, were obtained from partici-
pant charts and questionnaires. Baseline information
was obtained from each participant before diskography
via the Functional Rating Index (FRI), Numeric Rating
Scale (NRS), and the 36-Item Short Form Health Survey
(SF-36) questionnaires. Each participant was then
required to complete repeat questionnaires that also
included a modified North American Spine Society
(NASS) Outcome Questionnaire at 1 week, 4 weeks, 8
weeks, 6 months, and 12 months or more postinjection.
At enrollment, typically 2 weeks before treatment,
participants provided informed consent, a baseline
assessment, and blood samples via venipuncture to
assess white blood cell count, erythrocyte sedimenta-
tion rate, prothrombin time, and International
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3. Normalized Ratio INRQ2 to ensure all values were within
normal limits. Just before diskography, a blood sample
of 30 mL was drawn from all participants to ensure
participant blinding to treatment. All blood samples
were processed via a Harvest Technologies Corporation
(Plymouth, MA) centrifuge to produce 3-4 mL of autol-
ogous PRP for each participant.
The participants were randomized into 2 parallel
groups, the treatment or the control group (2:1 ratio,
respectively), by an independent observer who drew a
card from a sealed envelope. A 2:1 ratio of sealed en-
velopes, containing treatment or control cards, was
prepared by the independent observer before the initial
participant recruitment.
A covered syringe containing 3-4 mL of PRP (treat-
ment group) or contrast agent (control group) was then
prepared under a standardized protocol. The entire
syringe was covered with an opaque sleeve by an inde-
pendent observer to ensure its contents were not
visible. The participant was taken to the interventional
Table 1
Inclusion and exclusion criteria for study participation
Inclusion Criteria Exclusion Criteria
Refractory low back pain persisting for !6 mo
Failure of conservative treatment measures
(oral medications, rehabilitation therapy,* and/or injection
therapy)
Maintained intervertebral disk height of at least 50%
Disk protrusion less than 5 mm on magnetic resonance imaging
or computed tomography scan
Concordant pain on diskography
Presence of a grade 3 or 4 annular fissure as determined
by diskography
Absent contraindications (eg, spinal stenosis)
Presence of a known bleeding disorder
Current anticoagulation therapy
Pregnancy
Systemic infection or skin infection over the puncture site
Allergy to contrast agent
Presence of a psychiatric condition (eg, posttraumatic stress
disorder, schizophrenia)
Solid bone fusion preventing access to the disk
Severe spinal canal compromise at the levels to be investigated
Extrusions or sequestered disk fragments
Previous spinal surgery
Spondylolysis
Spondylolisthesis
Discordant pain on diskography
Presence of a grade 5 annular fissure with demonstrated
extravasation of contrast
* Note: Our standard physical therapy prescription focuses on patient education regarding proper ergonomics, back care principles, and pro-
gressive exercise instruction to increase core strength and flexibility in a spine safe manner. The program trial is usually twice weekly for a
minimum of 6 weeks.
printweb4C=FPOprintweb4C=FPO
Figure 1. Flow chart of study participant enrollment, randomization, and analysis.
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4. procedure suite and placed prone on the fluoroscopy
table. After a standardized sterile preparation, local
anesthesia was administered. With a standard double-
needle, extrapedicular technique, a 25-gauge spinal
needle was advanced through a 20-gauge introducer
needle into the mid-portion of the suspected disk levels,
as well as into a control level. Anteroposterior and
lateral fluoroscopic imaging confirmed proper needle
position. A volume of 1-2 mL of contrast agent (Omni-
paque 180, Amersham Health, Princeton, NJ) was
injected while the participant’s pain response and disk
architecture were recorded.
As soon as the participant endorsed concordant pain
reproduction and there was evidence of contrast filling an
annular fissure, the covered syringe was attached to the
needle hub by an independent physiatrist to maintain
blinding. No extension tubing was used during the injec-
tion. Only disk levels that elicited concordant pain with
evidence of incomplete annular disruption (2 mL) were
then injected additionally with either 1-2 mL of PRP or
1-2 mL of contrast agent. Both the physician and partic-
ipant remained blinded. If more than one disk was
symptomatic with reproduction of concordant pain, the
PRP or contrast was divided into equal doses and injected
into each of the affected disks. All participants had a
peripheral intravenous access placed and received 1 g of
cefazolin (AncefQ3 ) 30 minutes before the procedure.
Postdiskography computed tomography scan images,
when obtained, were used by the treating physician to
visualize and categorize the architecture of the IVD
according to the Dallas Discogram Classification [23].
This same information could later be used for surgical
decision-making if necessary. The treating physicians
remained blinded to the computed tomography scan
images during the initial 8-week follow-up period.
Follow-up questionnaires were then administered by
an independent observer at the designated time points.
After 12 months, a small subset of participants were
tracked annually for up to 2 years. All participants who
had no clinical improvement (ie, those who did not meet
or surpass the minimal clinically significant outcome
measure improvements) at 8 weeks were unblinded. If
they were initially in the control group, they were
offered intradiskal PRP for their symptomatic disk(s).
Those in the PRP group who had no clinical improvement
were managed with other continued conservative
treatments, or went on to surgery.
Outcome Measures
Primary outcomes measures included postprocedure
improvements in pain, function, and participant satis-
faction. Secondary outcomes were untoward side
effects, including increased pain, bleeding, infection,
and neurologic deficits. Four internationally validated
surveys were used as outcome measures: the FRI, the
NRS, the SF-36, and the modified NASS Outcome
Questionnaire. Only the physical functioning and pain
sections were scored on the SF-36 [24,25]. The FRI was
designed for participants with spinal disorders to mea-
sure participant perception of function and pain related
to performing dynamic movements and holding static
positions [26]. The minimum clinically important dif-
ference (MCID) of the FRI is a 9-point change [27]. The
NRS for pain is commonly presented as a 100-mm hori-
zontal line on which pain intensity is indicated by a
point between 0, ie, “no pain at all” and 10, ie, “worst
pain imaginable.” Participants were asked to tick an
integer representing current pain, pain at best, and pain
at worst [28]. The MCID of the NRS is a 2-point change
[29]. A change of 4.9 and 10 points constitute a MCID in
the SF-36 physical functioning and SF-36 pain scores,
respectively [28,30]. The modified NASS Outcome
Questionnaire measures participant satisfaction with
the procedure. The questionnaire used in this study is a
version of a questionnaire used in prior studies by other
authors [31,32].
A sample size of participants (48 treatment partici-
pants, 24 control participants) was estimated by power
analysis to achieve greater than 80% power to detect a
9-point change in FRI score with estimated standard
deviations of plus or minus 15 in a 2-way repeated
measures analysis of variance model with 5 time points.
Statistical Analysis
Overall summary statistics were calculated in terms
of means and standard deviations for continuous vari-
ables and frequencies, and percentages for discrete
variables. Baseline group differences for continuous
variables were evaluated using independent sample
t-tests, and c2
/Fisher exact tests were used for the
discrete variables. To assess the differences in partici-
pant reported outcome measures between PRP and
control groups over time and to adjust for missing data
at any given time point and the variation of the duration
of follow-up time, generalized linear mixed-effect
models were built. Multiple models were built to eval-
uate model fit based on variance-covariance structures.
On the basis of the results from the À2 Log Likelihood,
the Akaike Information Criterion, and Schwarz Bayesian
Criterion, final models with an unstructured variance-
covariance structure were reported [33]. Analysis of
the within-group changes over time for the PRP group
were assessed with a similar model. Bonferroni correc-
tions were applied to the analyses of inter- and
intragroup changes over time by multiplying the corre-
sponding P-values by factors of 3 and 5, respectively, to
account for multiple comparisons [34,35]. The effective
level of significance was .05 for all reported P-values.
Differences in mean PRP group scores at discrete follow-
up time points compared with those at baseline were
assessed using paired t-tests. Measures of the associa-
tion between treatment group and participant-reported
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5. satisfaction were calculated using odds ratios with
observed level of significance determined by Pearson
c2
test. Statistical significance for measures of associ-
ation was set to .05. All analyses that estimated mar-
ginal means for levels of factors and factor interactions
were conducted using SPSS version 20.0 (IBM Corp.,
Armonk, NY).
Results
PRP Versus Control Evaluation
From 2009 to 2013, 109 participants were assessed for
lumbar back pain for potential eligibility by the senior
investigator (G.E.L.). Of those participants, 26 failed to
meet the full inclusion and exclusion criteria, and 25
declined to participate in the study. The final number of
participants that were randomized was 58 participants
(53.2%). Of those 58 participants, 36 were randomized
to the treatment group (62.1%) and 22 were randomized
to the control group (37.9%). In the treatment group, 29
of the 36 participants were used for analysis (80.6%),
whereas 18 of the 22 control group participants were
used (81.2%).
Demographic characteristics in the 2 study groups are
reported in Table 2 Q4. Mean age between the 2 groups
were not significantly different. The control group had a
mean age of 44 years and the treatment group had a
mean age of 41 years (P ¼ .36). There was a significantly
greater proportion of female patients who were ran-
domized to the control group (84.2%) than there was in
the treatment group (51.7%) (P ¼ .03) (Table 2).
During the 8-week follow-up period in the compara-
tive component of the study, the PRP group demon-
strated significant improvement in several outcome
measures. The interaction effect of the between group
comparisons over 8 weeks showed a significant effect in
FRI score, indicating that the PRP group had significantly
changed over 8 weeks compared with changes in the
control group (P ¼ .03) (Table 3). Participant-reported
NRS best pain score showed a significant difference
over 8 weeks compared with the control group (P ¼ .02).
Group changes over 8 weeks were not found to be sig-
nificant in the self-reported current pain, worst pain,
SF-36 Pain, and SF-36 Function scores (P ¼ .16, P ¼ .09,
P ¼ .08, and P ¼ .44 respectively) (Table 3). Changes in
PRP and control groups over time are illustrated in
Figures 2-7.
At 8 weeks, participants who received PRP were more
likely to report satisfaction with their treatment than
Table 3
Results of patient-reported outcome scores between control and PRP groups over time
Outcome Time Control Mean SD PRP Mean SD P Value*
FRI Baseline 45.37 15.61 51.47 15.62 .027
1 wk 45.99 15.74 49.83 15.72
4 wk 44.17 17.14 43.25 16.68
8 wk 44.45 19.60 37.99 19.60
SF-36 Pain Baseline 47.92 21.13 43.28 21.11 .079
1 wk 47.22 21.76 40.52 21.76
4 wk 47.22 19.98 55.17 19.98
8 wk 52.78 22.19 61.29 22.19
SF-36 Physical Function Baseline 56.11 18.54 56.40 18.52 .435
1 wk 51.28 20.04 51.63 20.46
4 wk 60.97 21.43 58.43 21.17
8 wk 57.08 22.91 61.70 22.89
Current Pain Baseline 4.61 2.21 4.74 2.21 .157
1 wk 4.78 1.99 4.21 1.99
4 wk 4.61 2.21 4.00 2.21
8 wk 4.39 2.59 3.09 2.59
Best Pain Baseline 2.08 1.74 2.81 1.78 .015
1 wk 2.44 1.82 2.88 1.83
4 wk 2.28 1.82 2.53 1.83
8 wk 2.72 2.12 2.00 2.06
Worst Pain Baseline 7.72 1.53 7.98 1.56 .086
1 wk 7.39 1.95 6.86 1.94
4 wk 7.11 1.91 6.41 1.88
8 wk 6.83 2.33 5.82 2.33
PRP ¼ platelet-rich plasma; SD, standard deviation; FRI ¼ Functional Rating Index; SF-36 ¼ 36-Item Short Form Health Survey.
* P-value indicates significance of interaction effect of treatment over time.
Table 2
Baseline patient characteristics and patient reported outcome scores
between control and PRP groups
Control Mean
or N
Control SD
or %
PRP Mean
or N
PRP SD
or %
P
Value
N 18 29
Age 43.80 8.91 41.40 8.08 .359
Female gender 16 84.2% 15 51.7% .031
PRP ¼ platelet-rich plasma; SD ¼ standard deviation.
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6. those in the control group. Among the PRP group, 56%
(15/27) of the participants were satisfied with or would
undergo the same treatment compared with 18% (3/17)
of control participants. The odds of a participant in the
control group being dissatisfied was 5.83 times the odds
of a participant in the PRP group being dissatisfied (odds
ratio: 5.83, 95% confidence interval 1.17 to 37.47, P ¼
.01) (Table 4).
PRP Longitudinal Data
Longitudinal analysis of the PRP group consisted of 28
participants who reached the 6-month follow-up time
point and 21 participants who reached the 1-year time
point. Statistically significant improvements from
baseline to 6 months were observed in NRS Worst Pain
(1.66-point change) (P .01), FRI (12.92-point change)
(P .01), and SF-36 Pain (14.67-point change) (P ¼ .03).
Statistically significant improvements from baseline to 1
year were observed in NRS Worst Pain (2.12-point
change) (P .01), FRI (17.49-point change) (P .01),
SF-36 Pain (24.51-point change) (P .01), and SF-36
Physical Functioning scores (16.80-point change) (P
.01) (Table 5). PRP and control group outcomes were not
compared after 8 weeks.
Safety
There were no reported complications after the
intradiskal injection of PRP or additional contrast.
Discussion
This preliminary study was designed to evaluate the
clinical effectiveness of intradiskal autologous PRP for a
subset of participants with chronic lumbar diskogenic
printweb4C=FPOprintweb4C=FPO
Figure 4. Change in 36-Item Short Form Health Survey (SF-36) Physical
Function over time from baseline to 8 weeks for control and platelet-
rich plasma (PRP) groups. N indicates the number of observations
analyzed at the given time point.
printweb4C=FPOprintweb4C=FPO
Figure 2. Change in Functional Rating Index over time from baseline to
8 weeks for control and platelet-rich plasma (PRP) groups. N indicates
the number observations analyzed at the given time point.
printweb4C=FPOprintweb4C=FPO
Figure 5. Change in Numeric Rating Scale (NRS) Current Pain over time
from baseline to 8 weeks for control and platelet-rich plasma (PRP)
groups. N indicates the number of observations analyzed at the given
time point.
printweb4C=FPOprintweb4C=FPO
Figure 3. Change in 36-Item Short Form Health Survey (SF-36) Pain
Score over time from baseline to 8 weeks for control and platelet-rich
plasma (PRP) groups. N indicates the number of observations analyzed
at the given time point.
6 Lumbar Intradiskal PRP Injections
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7. pain. To our knowledge, this is one of the first clinical
studies investigating the efficacy of an intradiskal cell
therapy in a double-blind, randomized controlled study
design.
The strengths of this study were its double-blind,
randomized, controlled trial design, the rigorous
participant selection process, the high follow-up rate,
and long term data (ie, at least 1 year) in the majority of
participants. Although the number of participants was
relatively low, this study detected statistically signifi-
cant improvements in NRS Best Pain, FRI, and NASS
satisfaction between the treatment and control groups
over 8 weeks. In addition, the beneficial effects of PRP
were sustained for at least 1 year with respect to the FRI
Index. No participant in the treatment group experi-
enced complications, including progressive disk hernia-
tion, neurologic injury, or disk space infection.
Meticulous participant selection was critical for the
study. Inclusion and exclusion criteria were rigorous,
thus explaining the 4-year time period necessary to
enroll 51 eligible participants. Among the authors, it
was agreed that PRP is a targeted annular therapy. If the
disk protrusion was significant (5 mm) and the end-
plates were degenerated, targeted annular therapy
would likely be of no clinical or functional benefit.
Complete, Grade V annular fissures also were excluded,
because then the injectate would likely flow out of the
disk into the epidural space. This would allow little to
no opportunity for the PRP graft to effect an intradiskal
pro-healing change.
Interestingly, participants who elicited concordant
pain at 2 levels and were treated with PRP for both disks
showed superior improvements in all outcome measures
at 1 year compared with those participants who elicited
concordant pain at one level and subsequently received
treatment for the single disk. There were no significant
differences in mean outcome measure scores at base-
line between these 2 subgroups.
The least amount of contrast necessary to elicit a
pain response was injected in the IVD with the intention
of leaving sufficient space in the disk to accommodate
PRP volume. We did not use a pressure-controlled
manometry system because in the authors’ experi-
ence, these systems require greater volume of contrast
to elicit a pain response compared to manual adminis-
tration. In most participants, a pain response was eli-
cited with injection of less than 1 ml of contrast. In a
small group of participants, 2 mL of contrast was
required. In the authors’ experience, a disk that is not
completely disrupted will typically only hold 3-4 mL of
injectate. This limited the volume of PRP in most par-
ticipants to between 1 and 2 mL. Furthermore, for each
participant, treatment was limited to 1 injection at the
time of diskography to minimize the possibility of
adverse reaction from multiple disk punctures [36].
One limitation of the study was the limited follow-up
time of only 8 weeks for the control group. Having a
longer follow-up interval on the control participants (6
months, 1 year) would possibly enable detection of
greater differences between groups over time. Although
there were statistically significant differences between
PRP and control groups over 8 weeks, these changes
were not detected in all outcome measures, and the
changes in NRS pain scores were modest at best. In
retrospect, there were some participants in the study
who had more disk degeneration and larger protrusions
than others, which likely increased some of the vari-
ability in witnessed responses. Finally, there was no
data collection on cell counts or biochemical analysis of
the PRP and there was no routine radiologic follow-up to
see if morphologic disk changes occurred with clinical
improvement. Future studies should include these data
to better learn about the effects of cell therapy on
lumbar disk disease.
printweb4C=FPOprintweb4C=FPO
Figure 6. Change in Numeric Rating Scale (NRS) Best pain over time
from baseline to 8 weeks for control and platelet-rich plasma (PRP)
groups. N indicates the number of observations analyzed at the given
time point.
printweb4C=FPOprintweb4C=FPO
Figure 7. Change in Numeric Rating Scale (NRS) Worst Pain over time
from baseline to 8 weeks for control and platelet-rich plasma (PRP)
groups. N indicates the number of observations analyzed at the given
time point.
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8. A priori power analysis had indicated that a sample size
of 72 participants (48 treatment participants, 24 control
participants) was necessary to achieve greater than 80%
power to detect a 9-point change in FRI score with esti-
mated standard deviations of plus or minus 15 in a 2-way
repeated measures analysis of variance model with 5 time
Table 4
North American Spine Society (NASS) satisfaction at 8 weeks
Outcome Score
Control PRP
Odds Ratio
95% Confidence
Interval
P-ValueN % N % Lower Upper
NASS satisfaction at 8 wk 1 or 2 3 17.6% 15 55.6% 5.83 1.17 37.47 .010
3 or 4 14 82.4% 12 44.4%
The NASS Patient Satisfaction Index:
1 ¼ The procedure met my expectations.
2 ¼ I improved less than I had hoped, but I would undergo the same procedure again for the same results.
3 ¼ The procedure helped, but I would not undergo the same procedure again for the same results.
4 ¼ I am the same or worse than before the procedure.
Table 5
Results of patient-reported outcome scores for PRP group over time
Outcome Time N Mean SD P-Value*
FRI Baseline 29 51.47 15.62 Ref
1 wk 29 49.83 15.72 1.000
4 wk 27 43.25 16.68 .001
8 wk 29 37.99 19.60 .001
6 mo 28 38.55 21.80 .001
1 y 21 33.98 20.35 .001
P-value over time†
.001
SF-36 Pain Baseline 29 43.28 21.11 Ref
1 wk 29 40.20 21.76 .999
4 wk 29 55.17 19.98 .015
8 wk 29 61.29 22.19 .001
6 mo 28 57.95 25.45 .030
1 y 21 67.79 23.51 .001
P-value over time†
.001
SF-36 Physical Function Baseline 29 56.40 18.52 Ref
1 wk 29 51.63 20.46 .353
4 wk 28 58.43 21.17 .999
8 wk 29 61.70 22.89 .923
6 mo 28 67.14 24.18 .195
1 y 21 73.20 19.38 .001
P-value over time†
.001
Current Pain Baseline 29 4.74 2.21 Ref
1 wk 29 4.21 1.99 .436
4 wk 29 4.00 2.21 .215
8 wk 29 3.09 2.59 .001
6 mo 28 3.60 2.49 .091
1 y 21 3.15 2.38 .063
P-value over time†
.007
Best Pain Baseline 29 2.81 1.78 Ref
1 wk 29 2.88 1.83 .999
4 wk 29 2.53 1.83 .999
8 wk 28 2.00 2.06 .036
6 mo 28 2.00 2.33 .308
1 y 21 2.10 2.20 .999
P-value over time†
.040
Worst Pain Baseline 29 7.98 1.56 Ref
1 wk 29 6.86 1.94 .001
4 wk 28 6.41 1.85 .001
8 wk 29 5.82 2.33 .001
6 mo 28 6.32 2.12 .001
1 y 21 5.86 2.20 .002
P-value over time†
.001
PRP ¼ platelet-rich plasma; SD ¼ standard deviation; FRI ¼ Functional Rating Index; SF-36 ¼ 36-Item Short Form Health Survey.
* P-value compares difference from baseline using paired t-test.
†
P-value indicates significance of overall change over time.
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9. points. However, stopping rules were applied because of
logistical concerns (ie, time and financial constraints) and
an overwhelming number of control patients requesting
to be unblinded from the study protocol and requesting
the treatment specifically after the 8-week follow-up
period (n ¼ 15, 68.2%). As a result, the comparative
analysis was modified from 5 time points to 4. Given the
new parameters of the study, we were slightly under-
powered to detect the demonstrated difference in FRI
score at 8 weeks between the study groups. As an addi-
tional consequence, the variance-covariance matrix of
the original power analysis was not used for actual anal-
ysis of collected data. However, given the sample sizes
used for this study, we were adequately powered to
detect a 10-point difference between groups with a four
time point study design.
Conclusion
Participants who received intradiskal PRP experi-
enced significantly greater improvements in FRI,
NRSeBest Pain, and NASS satisfaction scores compared
with those who received contrast agent alone over 8
weeks. Additionally, the significant improvement in FRI
score was sustained for up to 1 year or more after PRP
injection. Under sterile conditions, intradiskal PRP
seems to have an excellent safety profile. There were
no reported complications after injection among
enrolled participants. Although these results are
encouraging, further studies are needed to determine
who the best candidates are for this treatment, what
the optimal PRP concentration and composition is,
whether multiple injections improve or worsen out-
comes, and how the cellular physiology responsible for
IVD regeneration can be considered to optimize the
therapeutic effect.
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Disclosure
Y.A.T.-W. Hospital for Special Surgery, Physiatry Department, New York, NY
Disclosures related to this publication: grant, Harvest Technologies unrestricted
research grant (money to institutionQ1 )
A.T. Hospital for Special Surgery, Physiatry Department, New York, NY
Disclosures related to this publication: grant, Harvest Technologies unrestricted
research grant (money to institution)
K.B.-A. Hospital for Special Surgery, Physiatry Department, New York, NY
Disclosures related to this publication: grant, Harvest Technologies unrestricted
research grant (money to institution)
J.R.H. Hospital for Special Surgery, Physiatry Department, New York, NY
Disclosure: nothing to disclose
C.K.G. Hospital for Special Surgery, Physiatry Department, New York, NY
Disclosures related to this publication: grant, Harvest Technologies unrestricted
research grant (money to institution)
E.E.L. Hospital for Special Surgery, Physiatry Department, New York, NY
Disclosures related to this publication: grant, Harvest Technologies unrestricted
research grant (money to institution)
J.T.N. Hospital for Special Surgery, Epidemiology and Biostatistics Department,
New York, NY
Disclosures related to this publication: grant, Harvest Technologies unrestricted
research grant (money to institution)
J.L.S. Hospital for Special Surgery, Physiatry Department, New York, NY
Disclosures related to this publication: grant, Harvest Technologies unrestricted
research grant (money to institution)
G.E.L. Hospital for Special Surgery, Physiatry Department, 429 E 75th St, 3rd
floor, New York, NY 10021. Address correspondence to: G.E.L.; e-mail: LutzG@
hss.edu
Disclosures related to this publication: grant, Harvest Technologies unrestricted
research grant (money to institution)
Disclosures outside this publication: consultancy, Biorestorative Therapies
medical advisor (money to author); stock/stock options, Biorestorative Thera-
pies (money to author)
This research was partially supported by a donation of study equipment from
Harvest Technologies. Mr. Nguyen was partially supported by Clinical Trans-
lational Science Center (CTSC) (UL1-RR024996).
An interim analysis of this study was presented at the October 2013 American
Academy of Physical Medicine and Rehabilitation conference.
Submitted for publication March 4, 2014; accepted August 13, 2015.
10 Lumbar Intradiskal PRP Injections
FLA 5.4.0 DTD Š PMRJ1567_proof Š 14 September 2015 Š 4:33 pm Š ce
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