Effect of an Intraoperative Periradicular Application of Platelet-rich Fibrin (PRF) on Residual Post-surgical Neuropathic Pain After Disc Herniation Surgery: Study Protocol for NeuroPRF, a Randomized Controlled Trial

Overview

Journal Trials

Publisher Biomed Central

Specialties General Medicine
Pharmacology

Date 2023 Jun 19

PMID 37337269

Authors

Julien Todeschi

Guillaume Dannhoff

Andres Hugo Coca

Daniel Ionut Timbolschi

Francois Proust

Francois Lefebvre

Vincent Lelievre

Pierrick Poisbeau

Laurent Vallat

Eric Salvat

Yohann Bohren

Affiliations

Soon will be listed here.

Abstract

Background: The prevalence of post-surgical lumbar neuropathic radiculopathy is approximately 30%. Poor response to the recommended treatments for neuropathic pain, namely antidepressants and/or gabapentinoids, requires the development of new techniques to prevent chronic pain. One such well-tolerated technique is the administration of autologous plasma enriched in platelets and fibrin (PRF). This approach is largely used in regenerative medicine owing to the anti-inflammatory and analgesic properties of PRF. It could also be an interesting adjuvant to surgery, as it reduces neurogenic inflammation and promotes nerve recovery, thereby reducing the incidence of residual postoperative chronic pain. The aim of the present study is to evaluate the benefit of periradicular intraoperative application of PRF on the residual postsurgical neuropathic pain after disc herniation surgery.

Methods: A randomized, prospective, interventional, controlled, single-blind study with evaluation by a blind outcome assessor will be performed in Strasbourg University Hospital. We will compare a control group undergoing conventional surgery to an experimental group undergoing surgery and periradicular administration of PRF (30 patients in each arm). The primary outcome is the intensity of postoperative neuropathic radicular pain, measured by a visual analog scale (VAS) at 6 months post-surgery. The secondary outcomes are the characteristics of neuropathic pain (NPSI), the quality of life (SF-12 and PGIC), the presence of anxiety/depression symptoms (HAD), and the consumption of analgesics. We will also carry out transcriptomic analysis of a panel of pro- and anti-inflammatory cytokines in blood samples, before surgery and at 6 months follow-up. These gene expression results will be correlated with clinical data, in particular, with the apparition of postoperative neuropathic pain.

Discussion: This study is the first randomized controlled trial to assess the efficacy of PRF in the prevention of neuropathic pain following surgery for herniated disc. This study addresses not only a clinical question but will also provide information on the physiopathological mechanisms of neuropathic pain.

Trial Registration: This study is registered at ClinicalTrials.gov: NCT05196503 , February 24, 2022.

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Fouad S, Rizk A, Mosbah E, Nabeeh M, Awadin W, Elmezayyen A BMC Neurosci. 2025; 26(1):10.

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References

Markman J, Kress B, Frazer M, Hanson R, Kogan V, Huang J . Screening for neuropathic characteristics in failed back surgery syndromes: challenges for guiding treatment. Pain Med. 2014; 16(3):520-30. DOI: 10.1111/pme.12612. View

Ware Jr J, Kosinski M, Keller S . A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996; 34(3):220-33. DOI: 10.1097/00005650-199603000-00003. View

Schmid A, Fundaun J, Tampin B . Entrapment neuropathies: a contemporary approach to pathophysiology, clinical assessment, and management. Pain Rep. 2020; 5(4):e829. PMC: 7382548. DOI: 10.1097/PR9.0000000000000829. View

Huh Y, Ji R, Chen G . Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain. Front Immunol. 2017; 8:1014. PMC: 5567062. DOI: 10.3389/fimmu.2017.01014. View

Raouf M, Wang X, Miusi S, Chai J, Mohamed AbdEl-Aal A, Nefissa Helmy M . Injectable-platelet rich fibrin using the low speed centrifugation concept improves cartilage regeneration when compared to platelet-rich plasma. Platelets. 2017; 30(2):213-221. DOI: 10.1080/09537104.2017.1401058. View

Bohren Y, Timbolschi D, Muller A, Barrot M, Yalcin I, Salvat E . Platelet-rich plasma and cytokines in neuropathic pain: A narrative review and a clinical perspective. Eur J Pain. 2021; 26(1):43-60. DOI: 10.1002/ejp.1846. View

Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J . Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain. 2005; 114(1-2):29-36. DOI: 10.1016/j.pain.2004.12.010. View

Carlsson A . Assessment of chronic pain. I. Aspects of the reliability and validity of the visual analogue scale. Pain. 1983; 16(1):87-101. DOI: 10.1016/0304-3959(83)90088-X. View

Leung L, Cahill C . TNF-alpha and neuropathic pain--a review. J Neuroinflammation. 2010; 7:27. PMC: 2861665. DOI: 10.1186/1742-2094-7-27. View

10.

Treede R, Jensen T, Campbell J, Cruccu G, Dostrovsky J, Griffin J . Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2007; 70(18):1630-5. DOI: 10.1212/01.wnl.0000282763.29778.59. View

11.

Ikumi A, Hara Y, Yoshioka T, Kanamori A, Yamazaki M . Effect of local administration of platelet-rich plasma (PRP) on peripheral nerve regeneration: An experimental study in the rabbit model. Microsurgery. 2017; 38(3):300-309. DOI: 10.1002/micr.30263. View

12.

Chenaf C, Delorme J, Delage N, Ardid D, Eschalier A, Authier N . Prevalence of chronic pain with or without neuropathic characteristics in France using the capture-recapture method: a population-based study. Pain. 2018; 159(11):2394-2402. DOI: 10.1097/j.pain.0000000000001347. View

13.

Lurie J, Tomkins-Lane C . Management of lumbar spinal stenosis. BMJ. 2016; 352:h6234. PMC: 6887476. DOI: 10.1136/bmj.h6234. View

14.

Mika J, Zychowska M, Popiolek-Barczyk K, Rojewska E, Przewlocka B . Importance of glial activation in neuropathic pain. Eur J Pharmacol. 2013; 716(1-3):106-19. DOI: 10.1016/j.ejphar.2013.01.072. View

15.

Thacker M, Clark A, Marchand F, McMahon S . Pathophysiology of peripheral neuropathic pain: immune cells and molecules. Anesth Analg. 2007; 105(3):838-47. DOI: 10.1213/01.ane.0000275190.42912.37. View

16.

Winkelstein B, Weinstein J, DeLeo J . The role of mechanical deformation in lumbar radiculopathy: an in vivo model. Spine (Phila Pa 1976). 2002; 27(1):27-33. DOI: 10.1097/00007632-200201010-00009. View

17.

Bouhassira D . Neuropathic pain: Definition, assessment and epidemiology. Rev Neurol (Paris). 2018; 175(1-2):16-25. DOI: 10.1016/j.neurol.2018.09.016. View

18.

Attal N, Lanteri-Minet M, Laurent B, Fermanian J, Bouhassira D . The specific disease burden of neuropathic pain: results of a French nationwide survey. Pain. 2011; 152(12):2836-2843. DOI: 10.1016/j.pain.2011.09.014. View

19.

Dohan Ehrenfest D, Rasmusson L, Albrektsson T . Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends Biotechnol. 2009; 27(3):158-67. DOI: 10.1016/j.tibtech.2008.11.009. View

20.

Kim H, Yeom J, Koh Y, Yeo J, Kang K, Kang Y . Anti-inflammatory effect of platelet-rich plasma on nucleus pulposus cells with response of TNF-α and IL-1. J Orthop Res. 2013; 32(4):551-6. DOI: 10.1002/jor.22532. View