The results of this study highlight the therapeutical impact of adding high-voltage PRF to EA and support its effectiveness in the treatment of lumbosacral NP. Pain relief in the PRF-EA group lasted longer if compared with patients undergoing adhesiolysis alone who experienced a drop off in benefits at 6 months. The pain improvement rates observed in this study were comparable with those reported in previous trials, although the range between studies may differ significantly.19,20
Some features of the present study need to be explained. First, we chose to treat patients with EA rather than TFESI, due to better results reported in people with chronic low back and radicular pain.38 Moreover in comparison with a needle-mediated approach, delivering PRF with a multifunctional flexible electrode allows a closer stimulation of the target and the chance to infuse medications into the epidural space. These features might increase neuromodulation of the dorsal root and improve the outcome without nerve injury, as postulated in previous studies.39 Pulsed radiofrequencies have shown positive effects against allodynia in animal models, therefore NP features might influence the response to treatment and need to be assessed before enrollment.40,41 If compared with conventional PRF, high-voltage stimulation showed better results in several NP models likely due to the generation of greater electric fields. In turn, this might be responsible for plastic changes in pain transmission pathways, accounting for slow onset and sustained effectiveness of high-voltage PRF.42–44
Current studies on lumbosacral pain often involve heterogenous study populations, due to not restrictive selection criteria. Nevertheless, this issue has been a matter of debate and has not yet yield to conclusive enrollment guidelines.45 More homogenous populations might improve diagnosis and therapeutical outcomes in future studies, improving our success rate in challenging disorders such as NP.46 Because PRF neuromodulation was reported to progressively fade away, effectiveness may vary significantly among studies with likely extended pain relief if treatments are repeated over time.47
Few issues and limitations of this study needs to be pointed out. In our opinion, the choice to compare PRF with a different treatment rather than placebo did not impair reliability of results. A small sample size might impair statistical power and lead to misinterpretation of results. Nevertheless, large population studies in analgesic trials have been proven to be challenging and hardly feasible. The sample size in our study provided us sufficiently high power to detect the treatment effects.48,49 The enrolled population featured patients with different pathologies, mostly with axial and radiating pain. If outcomes involved the evaluation of disability or subjective global satisfaction, the co-existence of LBP and radiculopathy might have affected our results, but excluding patients with LBP would extend duration of recruitment for years.50 Moreover, most of patients with chronic radiculopathies in the lower limbs reported axial pain at onset or in different stages of the disorder. Excluding patients with LBP might bias the results of the trial as the association of axial and radiating pain is the most common presentation in clinical practice. A female prevalence for chronic pain of neuropathic origin has been reported in epidemiological studies and can therefore explain sex difference in our study. Moreover, although being a potential risk factor in radicular pain, clinical improvement was not remarkably different between men and women at baseline and follow-up.6,51,52 Last, enrollment started almost 1 year before the revised NP clinical grading and therefore some of our patients were diagnosed with previous guidelines. However, we did not consider this to be a significant issue because differences between the 2 versions are mostly related to the “possible” NP allocation whereas patients enrolled in our study were in the “probable” or “definite” group.
This is the first randomized controlled trial showing the effectiveness of adding high-voltage PRF to EA in the treatment of NP due to chronic lumbosacral radiculopathy. If confirmed, these results might represent a significant step forward in the treatment of challenging NP syndromes, strengthening the importance of a broad consensus among pain physicians on the choice of devices and stimulation protocols. Therefore, the development of new randomized controlled trials testing long-term effects of PRF are encouraged to evaluate the contribution of the technique in pain management.
The authors thankfully acknowledge Walter Rossi, Patrizia Silvegni, Sara Buzzoni, Mara Desiderati (RN, Santa Maria Maddalena Hospital, Pain Medicine Unit), and Camilla Olivieri (Advanced Algology Research) for their significant assistance in supporting this project.
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