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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).

Single injections of autologous PRP into symptomatic degenerative IVDs will improve participant-reported pain and function.

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 randomized 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/exclusion criteria after undergoing the procedure, and 1 was lost to follow-up, yielding a follow-up rate of 92% (Figure 1).

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 practice and enrolled in the study if prediskography inclusion criteria were met. General demographic information, including age and gender, as well as baseline outcome scores, were obtained from participant 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 sedimentation rate, prothrombin time, and International Normalized Ratio (INR) 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 centrifuge (Harvest Technologies Corporation, Plymouth, MA) to produce 3-4 mL of autologous 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 envelopes, 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 (treatment group) or contrast agent (control group) was then prepared under a standardized protocol. The entire syringe was covered with an opaque sleeve by an independent observer to ensure its contents were not visible. The participant was taken to the interventional 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 (Omnipaque 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 injection. 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 participant 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 (Ancef; GlaxoSmithKline, Philadelphia, PA) 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.

Primary outcomes measures included postprocedure improvements in pain, function, and participant satisfaction. 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 measure participant perception of function and pain related to performing dynamic movements and holding static positions [26]. The minimum clinically important difference (MCID) of the FRI is a 9-point change [27]. The NRS for pain is commonly presented as a 100-mm horizontal 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 participants, 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.

Overall summary statistics were calculated in terms of means and standard deviations for continuous variables and frequencies, and percentages for discrete variables. Baseline group differences for continuous variables were evaluated using independent sample t-tests, and χ²/Fisher exact tests were used for the discrete variables. To assess the differences in participant 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 evaluate model fit based on variance-covariance structures. On the basis of the results from the −2 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 corrections were applied to the analyses of inter- and intragroup changes over time by multiplying the corresponding 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 association between treatment group and participant-reported satisfaction were calculated using odds ratios with observed level of significance determined by Pearson χ² test. Statistical significance for measures of association was set to .05. All analyses that estimated marginal means for levels of factors and factor interactions were conducted using SPSS version 20.0 (IBM Corp., Armonk, NY).