Letter to the Editor: Intradiscal platelet-rich plasma for discogenic low back pain - promise or premature adoption?

Abstract

The quasi-experimental study by Mounisamy et al, recently published in the World Journal of Orthopedics, reported 6-week within-group improvements in pain and function after intradiscal autologous platelet-rich plasma (PRP) treatment in patients with chronic lumbar disc prolapse who had failed physiotherapy. These findings align with a growing body of evidence, including systematic reviews and meta-analyses, which suggest that intradiscal PRP may be a safe and potentially effective treatment. However, the promise of this regenerative therapy approach is limited by the lack of high-quality studies on sustained functional improvement or structural regeneration. The field is further limited by methodological heterogeneity, including the absence of standardized protocols for PRP preparation and patient selection. The study by Mounisamy et al adds a pragmatic perspective; however, its short follow-up and non-randomized design highlight the need for large-scale, long-term, methodologically rigorous randomized controlled trials to better define the role of intradiscal PRP.

Key Words: Platelet-rich plasma; Discogenic low back pain; Intradiscal injection; Regenerative orthopedics; Quality of life

Core Tip: Current treatment options for discogenic low back pain remain limited in their ability to provide durable symptom relief and structural restoration. In this editorial, we discuss platelet-rich plasma (PRP) as a potential biological treatment. The growth factor content of PRP may help counteract disc catabolism, although it remains uncertain whether these mechanisms translate into meaningful clinical regeneration. Two randomized trials reported modest or no clear between-group benefit, whereas uncontrolled studies have suggested symptomatic improvement. A recent quasi-experimental study found early improvements in pain and function without major adverse events, although important confounding factors remained. Overall, the current evidence supports continued clinical equipoise, emphasis on patient-centered outcomes, and adequately powered, blinded trials before broader clinical adoption of intradiscal PRP.

TO THE EDITOR

Chronic low back pain (LBP) is one of the leading causes of disability worldwide. It remains a persistent public health and economic challenge[1]. Discogenic LBP is generally defined as pain arising from structural and biochemical changes within the intervertebral disc. In clinical practice and research, diagnosis usually relies on a combination of clinical features, imaging findings, and, in selected cases, provocative discography, although no universally accepted diagnostic gold standard exists[2]. Degeneration-related nociception from the intervertebral disc can be difficult to manage clinically. Imaging may not always accurately capture this pathology. In addition, discogenic pain may overlap with vertebrogenic or endplate-related pain, complicating diagnosis and patient selection[3]. Other factors, such as vertebrogenic pain associated with Modic changes or psychosocial determinants of chronic pain, may further influence patient selection and treatment response.

Conventional treatments, including exercise-based rehabilitation, analgesics, and injections, often provide incomplete or time-limited relief. In addition, surgery is not appropriate for many patients with mild to moderate degeneration who lack clear surgical indications. This therapeutic gap has prompted interest in strategies to restore disc function, including intradiscal platelet-rich plasma (PRP), due to its proposed regenerative and anti-inflammatory potential[4-6].

PRP delivers a high concentration of autologous growth factors that may stimulate extracellular matrix synthesis and modulate inflammatory signaling in degenerated discs[5]. However, the avascular and nutrient-poor environment of the intervertebral disc limits the potential for durable regeneration[3,7]. Consequently, biological plausibility alone does not guarantee meaningful clinical benefit.

SCIENTIFIC EVIDENCE

The number of studies on intradiscal PRP for discogenic LBP is small but growing. Two randomized controlled trials (RCTs) currently form the core of the available evidence. However, they point in different directions. Tuakli-Wosornu et al[8] reported findings from a double-blind RCT indicating a modest functional improvement at 8 weeks vs control (functional rating index favored PRP) with maintenance of within-group functional gains 1 year after treatment. However, there was no clear long-term between-group superiority across several outcomes, underscoring a result that is statistically suggestive but clinically equivocal.

In contrast, Zielinski et al[9] conducted a multicenter, placebo-controlled RCT that was underpowered due to early termination (26 randomized; 60 planned). They observed no significant differences between treatment with PRP or saline at 8 weeks on pain or disability. They reported no serious adverse events, reinforcing the concern that the apparent effect may be small and fragile due to the study design.

Additional observational studies have suggested symptomatic improvement after intradiscal PRP. However, all studies lacked concurrent controls. Therefore, causal inference was not possible, and a placebo or contextual effect cannot be excluded[10-12]. The World Journal of Orthopedics study by Mounisamy et al[13] employed a quasi-experimental design with 39 participants. Non-responders to a standardized McKenzie program received intradiscal autologous PRP while responders to the same program functioned as a pragmatic benchmark. At 3-6 weeks the authors found a statistically significant within-group improvement in pain and function in the PRP group with no major adverse events. The manuscript was carefully presented. The procedural steps were described in detail, validated outcomes were used, and effect sizes were reported. These features may enhance transparency and reproducibility. Nevertheless, the design was nonrandomized and unblinded, and group non-equivalence (responders vs non-responders) leads to residual confounding. Even if baseline characteristics appear broadly similar, causal attribution remains limited. In our view, this study produced hypothesis-generating data that enriches a sparse field rather than practice-changing evidence. As with many uncontrolled or quasi-experimental designs, regression to the mean and contextual effects cannot be excluded. Their results appropriately motivate adequately powered randomized trials with longer follow-up periods.

A rigorous appraisal of intradiscal PRP trials must begin with an assessment of internal validity. Without randomization, allocation concealment, and blinding, the benefits of PRP treatment are vulnerable to selection, performance, detection, and reporting biases. Even when statistical significance is achieved, trials must also demonstrate clinical relevance using patient-important outcomes and prespecified thresholds such as the minimal clinically important difference. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (also known as IMMPACT) recommends a core set for chronic pain (pain intensity, physical function, emotional function, patient global improvement/satisfaction, adverse events, and treatment disposition) so that isolated changes in scales or surrogate markers cannot guide practice[14,15].

Short follow-up windows compound uncertainty. Structural disc regeneration, if it occurs, would likely require longer timeframes to become detectable on imaging or to translate into sustained clinical improvement[16]. Early improvements in back pain trials may attenuate over time while regression to the mean and placebo/contextual effects can inflate within-group gains in uncontrolled or unblinded studies. Masked comparators and complete outcome reporting should become the standard practice in this field[17]. Finally, evidence-based decisions hinge on transparent benefit-risk calculus. When the benefit is uncertain or below minimal clinically important difference thresholds, the infrequent harms should be weighed more heavily. Therefore, robust trials must pair patient-centered endpoints with systematic adverse event analysis to justify adoption[14].

CONCLUSION

Given the limited scientific evidence, it is not yet possible to formally recommend intradiscal PRP for treating LBP. Until such evidence accrues, the prudent, patient-centered stance is to acknowledge biological plausibility while withholding routine clinical endorsement, maintaining balance in ongoing trials, and prioritizing transparent shared decision-making that accounts for uncertainties in efficacy and safety.