The present investigation involved a systematic review. A set of MeSH-based search queries were generated to explore research on utilization of PRP in management of vertebrogenic and discogenic pain (see Table 1). These queries encompass a range of relevant terms and concepts, aiding in the comprehensive retrieval of pertinent literature from medical databases such as PubMed, EuroPMC, WHO ICTRP, and Clinicaltrials.gov. We utilized the following search terms to systematically review available evidence on this topic: "Platelet-rich plasma," "Vertebrogenic Pain," and "Discogenic Pain", facilitating a thorough investigation into potential benefits and outcomes associated with PRP therapy for individuals suffering from vertebrogenic or discogenic pain. Additionally, we performed manual searching as part of our systematic review process.

In terms of inclusion criteria, we included randomized controlled trials (RCTs) that focus on PRP as a treatment for vertebrogenic or discogenic pain in individuals of greater than 18 years of age. These studies compared PRP treatment with standard care, placebo, or alternative interventions and report outcomes related to pain reduction, functional improvement, quality of life, adverse events, or radiological assessments. Excluded from our analysis were case reports, case series, animal studies, letters, editorials, and conference abstracts. Studies not related to vertebrogenic or discogenic pain, those involving regenerative therapies other than PRP, lacking relevant comparators, or not reporting relevant outcome data were excluded. Additionally, studies published in languages other than English were excluded, unless translation resources were adequate.

In this systematic review, the process of determining whether a study met the inclusion criteria of the review was conducted with a structured and rigorous approach. All authors were responsible for screening each record and report retrieved, working independently of each other to minimize bias. Automation tools were not utilized in this process; instead, the reviewers manually assessed each record and report to ensure a comprehensive and thorough evaluation. In cases where discrepancies or disagreements arose between reviewers regarding the inclusion or exclusion of a particular study, a consensus meeting was convened to resolve differences through discussion and mutual agreement. If a consensus could not be reached, a senior reviewer was consulted to make the ultimate determination.

The primary outcomes included pain assessment, as measured through instruments such as the numerical rating scale (NRS), visual analogue score (VAS) and numerical pain scale (NPS), as well as disability evaluation employing the Oswestry Disability Index (ODI). These evaluations encompassed the determination of both absolute scores and alterations from baseline scores at various time intervals, including baseline and follow-up periods post-PRP injection. Measures of effect was derived in two distinct approaches. First, the average absolute value for each time point was computed, entailing calculation of mean pain or disability scores across the entire patient cohort at a specific time interval. Secondly, mean difference for each time point concerning baseline values was determined, signifying change in pain or disability scores relative to values recorded prior to cell- or PRP injection.

The data extraction process for this study followed a methodical approach. Initially, potential articles were subjected to a two-stage screening process. Data extraction was carried out using a standardized sheet, with all reviewers independently recording evaluations of study design, patient characteristics, and treatment particulars. Moreover, various outcome measures, such as VAS, NPS, or NRS, ODI disability scores, or other scoring system. Additionally, quantitative data pertaining to quality of life, radiographic outcomes, and adverse event was extracted.

The Cochrane Risk of Bias (ROB) tool, developed by the Cochrane Collaboration, is a methodological framework used to assess internal validity of studies, particularly randomized controlled trials (RCTs), included in systematic reviews and meta-analyses by three independent authors (JH, UD, and SK). It evaluates various domains, including random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other potential sources of bias. Each domain is rated as "unclear", "low," or "high" risk of bias based on available information, and an overall risk of bias for a study is determined through collective assessments. The Cochrane ROB tool aids in transparently gauging the reliability and trustworthiness of evidence, facilitating informed judgments about the quality of studies incorporated into current systematic reviews and meta-analyses.

To conduct a meta-analysis, Review Manager 5.3 (Copenhagen: The Cochrane Collaboration, 2014) was employed. Continuous variables were expressed as means accompanied by mean standard deviations (MSDs), computed using the inverse-variance methodology. Utilizing random effects models regardless of heterogeneity, mean standard differences (MSDs) for continuous variables were presented with confidence intervals (CIs) of 95%. Employing a two-tailed P-value, statistical significance was established at ≤ 0.05. Assessment of heterogeneity involved the Q-statistic test and the I2 test. The I2 statistic quantified the proportion of overall variability stemming from clinical or methodological heterogeneity as opposed to chance. Significance (P < 0.05) in the Q statistics denoted heterogeneity among the studies, with I2 values exceeding 50% indicating substantial heterogeneity.