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Review Article
2026
:5;
100725
doi:
10.1016/j.jorep.2025.100725

A systematic review of the clinical application of platelet-rich plasma for peripheral neuropathic pain

, , , ,
a Department of Plastic & Reconstructive Surgery, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
b Department of Physical Medicine and Rehabilitation, Sports Medicine Research Institute, The Ohio State University, Columbus, OH, 43210, USA

∗Corresponding author: Amy M. Moore. amy.m.moore@osumc.edu

Received: , Accepted: ,
The Authors
Disclaimer:
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Abstract

This review evaluates the efficacy of PRP in treating peripheral neuropathies, including carpal tunnel syndrome (CTS), ulnar neuritis, common peroneal nerve palsy, and piriformis syndrome.

Studies were identified through PubMed/Medline Mesh searches. A meta-analysis was conducted for prospective and retrospective studies, case series, and case reports examining the impact of PRP on peripheral neuropathic pain all articles, but statistical analysis was only conducted on CTS studies, given the paucity of literature pertaining to the other anatomical neuropathies. Statistical analysis included the changes in the mean values of the Visual Analog Scale (VAS) and Boston Carpal Tunnel Questionnaire Functional Status Scale (FSS) and Symptom Severity Scale (SSS) scores within and between treatment types. T-tests were conducted to determine a statistically significant difference in outcomes between intervention and control groups and pre- and post-intervention/control within groups.

A PubMed/Medline search identified 123 articles that were reviewed by two independent reviewers to determine articles that met inclusion and exclusion criteria. A total of 13 studies were included in the study: Carpal Tunnel Syndrome (n = 11), Ulnar Neuritis (n = 2), Common Peroneal Neuropathy (n = 1), and Piriformis Syndrome (n = 1). Eleven studies were included in the analysis of the clinical application of PRP for CTS, in which there were 224 control subjects and 208 experimental subjects, totaling 432 subjects. Controls in this study include those who received injections (D5W, saline, or corticosteroid), splinting, medical therapy, or carpal tunnel release surgery. The PRP group exhibited significant improvements in VAS, FSS, and SSS scores compared to the control group at six-months (p < 0.001). While surgical intervention demonstrated superior FSS and SSS scores at six-months than PRP (p < 0.001), PRP shows promise in the non-surgical management of carpal tunnel syndrome, ulnar neuritis, common peroneal nerve palsy, and piriformis syndrome.

This review suggests that PRP is a promising modality for managing peripheral neuropathic pain. PRP may serve as a valuable non-surgical alternative and potentially as an adjunct to more surgical interventions. Further research is needed to standardize PRP preparations and elucidate its long-term efficacy across various peripheral neuropathies.

Keywords

Platelet-rich plasma
Peripheral neuropathic pain
Nerve pain
PRP
1

1 Introduction

Neuropathic pain is detrimental to patients’ quality of life. 1Studies have shown that the current medical management of neuropathic pain has not been sufficient in the long term, as 45 % of neuropathic pain patients require at least two medications for appropriate management of pain, and accounts for about 20 % of emergency room visits.1–4 A 2019 algorithm recommended a series of steps with the use of medications and multimodal therapy including interventional therapy by pain specialists for refractory pain.5 Steroid injections, pulsed radiofrequency ablation, and if a patient has continued pain, further treatments include neuromodulation, low-dose opioids, and targeted drug delivery were described.4,5 While this algorithm provides an excellent overview of medical and interventional treatments, it does not describe the role nerve surgery has in the in the alleviation of neuropathic pain.

In recent years, the surgical management of neuropathic pain has emerged as a promising option as the field of nerve surgery has advanced its techniques and understanding of the surgical indications for pain. Techniques such as targeted muscle reinnervation (TMR), regenerative peripheral nerve interfaces (RPNIs), nerve transfers, and electrical stimulation have been reported as successful interventions.6–9 Caragher et al. suggest the use of multimodal, personalized medical therapies in conjunction with novel nerve surgeries will allow for future innovation to better alleviate neuropathic pain.10 However, there are limitations of surgical interventions such as cost, inherent risks, and comorbid conditions that may preclude patients from going to the operating room.

Platelet Rich Plasma (PRP) is an autologous solution with platelets concentrated over baseline.11 It has shown to be effective in various clinical conditions due to its ability to take advantage of the body's healing process by stimulating tissue repair through the release of growth factors and recruitment of repair cells.12 PRP has been employed in the treatment of numerous orthopedic and musculoskeletal diagnoses including osteoarthritis, tendon and ligament injuries, and degenerated nerves.13–16 It is suggested that PRP formulations may promote axonal regeneration through promotion of angiogenesis and the secretion of NGF and BDNF, both secreted by lymphocytes.17,18 Hence, this PRP-mediated axonal regeneration may reduce neuropathic pain through restoring normal biophysical properties of axons.17

Given the theoretical benefit of PRP and its favorable efficacy in the musculoskeletal literature, we sought to understand the clinical use of PRP in the treatment of peripheral neuropathy. In this study, we review the current clinical applications of PRP in peripheral neuropathy and aim to elucidate its efficacy in the treatment of neuropathic pain as it relates to the field of peripheral nerve surgery.

2

2 Methods

PubMed/Medline was searched in October 2024 for “((“Platelet-Rich Plasma" [Mesh]) AND “Peripheral Nerves" [Mesh])”, “(“Platelet-Rich Plasma" [Mesh]) AND “Neuralgia" [Mesh]”, and “neuropathy AND “Platelet-Rich Plasma”“. Inclusion criteria were original prospective and retrospective studies, case series, and case reports examining the impact of PRP on peripheral neuropathic pain. Exclusion criteria included articles about infectious neuropathies, animal models, meta-analyses, and studies without pre- or post-intervention measures. PRISMA Guidelines were adhered to (Table 1). Two independent reviewers examined these articles to verify inclusion and exclusion criteria. Data extracted included age, duration of symptoms, type of intervention, and pre- and post-intervention pain, function, symptoms, electrodiagnostic, and overall outcomes. This is shown in Table 2.

Table 1 PRISMA Guidelines for identification of appropriate studies.
Table 2 Studies included in meta-analysis.
Studies Included in Meta-Analysis
Condition Publication Title Authors PRP Preparation
Carpal Tunnel Syndrome Outcome predictors of platelet-rich plasma injection for moderate carpal tunnel syndrome Shen et al., 202121 RegentKit-THT-1 (RegenLab SA, Mont-sur-Lausanne, Switzerland) or PLTenus Plus Platelet Concentrate Separator (TCM Biotech International Corp, Taiwan) were used for PRP injections. A total of 10 ml of venous blood was centrifuged using Regen Lab PRP Centri with parameters set to 3400 rpm for 15 min at room temperature, producing approximately 3–3.5 mL of leukocyte-rich PRP. RegentKit-THT-1 contained anticoagulants (sodium citrate solution) and activators (autologous thrombin) to activate platelets and to convert fibrinogen to fibrin. A total of 7 ml of venous blood was centrifuged at 500–1200 G for 8 min at room temperature using PLTenus Plus Platelet Concentrate Separator, providing 3.5–4 ml leukocyte-poor PRP. The PLTenus Plus Platelet Concentrate Separator consisted of Anticoagulant Citrate Dextrose Solution-A without any activators.
Marrying tendon and nerve gliding exercises with hydrodissection following injection for carpal tunnel syndrome - A new treatment approach? Savage & Albano, 202022 Thirty milliliters (mL) whole blood drawn from antecubital vein using ENDORET® Technology (BTI Biotechnology Institute, Blue Bell, PA, USA) yielding 8.0 mL of plasma-rich growth factors containing 2–3 times baseline concentration of platelets with low red and white blood cell counts. Calcium chloride (0.02 cc/mL) added to preparation before injection.
Platelet-rich plasma in treatment of patients with idiopathic carpal tunnel syndrome Senna et al., 201923 Sixteen milliliters of blood was obtained from each patient using special PRP kits (GD medical pharma, Dutch company). The blood was collected on citrated tubes with a mixing ratio of 9:1 by volume. Tubes underwent first centrifugation at a speed of 3000 rpm (704 g) for 3 min (to separate red blood cells from plasma). Plasma was then re- moved by syringe and then placed into another sterile tube with no anti-coagulant and then underwent second centrifugation at a speed of 4000 rpm (1252 g) for 15 min. The super- natant platelet poor plasma was then removed leaving 2 ml of PRP pellets in the sediment, and suspend the PRP pellets by gentle shaking of the tube. PRP is activated by adding 200 μl of 0.025 calcium chloride.
Safety and efficacy of platelet-rich plasma in treatment of carpal tunnel syndrome; a randomized controlled trial Raeissadat et al., 201824 For preparing 1 mL of PRP, 10 mL of blood was initially drawn from the patient's upper limb cubital vein using an 18G needle. Then, 1 mL of ACD-A was added to the sample as an anticoagulant and passed two stages of centrifugation; first at 1600 rpm for 12 min to separate the erythrocytes and then at 3500 rpm for 7 min in order to concentrate the platelets. The resulting PRP contained leukocytes with mean concentrations of 5–10 %. Eventually, PRP quantification was performed to confirm that the platelet concentration has reached 4–6 times that of the whole blood, since some studies have shown a positive effect of PRP at this concentration in musculoskeletal diseases and others have indicated that concentrations higher than 8 times can negatively affect the repair process and inhibit cellular proliferation.
Six-month efficacy of platelet-rich plasma for carpal tunnel syndrome: A prospective randomized, single-blind controlled trial Wu et al., 201720 Ten milliliters of blood sample were drawn from the antecubital vein using RegentKit-THT-1 (RegenLab SA, Mont-sur-Lausanne, Switzerland) followed by centrifugation at 3400 rpm for 15 min at room temperature using Regen Lab PRP Centri, yielding 3.5 mL of PRP. The RegentKit-THT-1 has sodium citrate solution as an anticoagulant, and autologous thrombin as an activator to advance platelet activation and conversion of fibrinogen to fibrin. For quality tests, 0.5 mL of the PRP sample was sent to the laboratory and 3 mL was used for the ultrasound-guided injection. The concentration of platelets and leukocytes in the PRP was approximately 2.7 ± 0.4 times and 1.2 ± 0.4 times compared to that in whole blood, respectively.
Single injection of platelet-rich plasma as a novel treatment of carpal tunnel syndrome Malahias et al., 201525 Under sterile condition, 20 mL of autologous venous blood sample was taken from each patient's contralateral (non-affected) hand and then centrifuged at two consecutive density gradient centrifugations (total 3100 runs for 10 min) at the laboratory of our hospital. At the first centrifugation, red blood cells were separated, and at the second centrifugation, PRP was separated from the platelet poor plasma (PPP) and then transferred to sterile tubes.
Platelet-rich plasma injection versus surgical and medical treatment of mild-moderate carpal tunnel syndrome Eltabl et al., 202026 Platelet-rich plasma prepared by taken 10 ml of venous blood sample from every patient and was collected in sterile sodium citrated tubes. Then, the tubes with citrated blood were centrifuged at 3500 rpm (revolutions per minute) for 9 min to separate erythrocytes and produce about 1–2 ml of PRP for injection.
One-Year Efficacy of Platelet-Rich Plasma for Moderate-to-Severe Carpal Tunnel Syndrome: A Prospective, Randomized, Double-Blind, Controlled Trial Chen et al., 202127 Whole blood samples (7 mL) were collected from each patient by venipuncture from the antecubital vein using a PLTenus Plus Platelet Concentrate Separator; the anticoagulant used was Anticoagulant Citrate Dextrose Solution-A. The sample was centrifuged at 500–1200 g for 8 min and approximately 3.5–4.0 mL of leukocyte-poor PRP was then isolated.
Short-term effectiveness of platelet-rich plasma in carpal tunnel syndrome: a controlled study Güven et al., 201919 The solution was prepared manually by using double centrifuge method (Dohan Ehrenfest, Rasmusson, & Albrektsson, 2009). Venous blood was drawn from the patient to a sterile syringe containing 1.8 cc sterile acid citrate dextrose solution, summing the total content up to 10 cc. The sample was then transferred to a sterile BD Vacutainer No Additive tube, and centrifuged at a 100 g force for 15 min. After procedure, three layers were observed: red blood cell layer at the bottom, platelet poor plasma layer at the top, and buffy coat in the middle. The platelet poor plasma and buffy coat layers were aspirated and transferred to a sterile no additive tube and centrifuged at 1600 g force for 10 min. After the second centrifuge procedure, upper plasma portion was discarded, and the remaining 1 cc plasma with concentrated cellular elements at the bottom of the tube was aspirated to a sterile syringe to be used as the PRP solution. In order to verify the effectiveness of this method, five consecutive trials had been performed with blood samples acquired from healthy volunteers prior to the study, and fourfold to sixfold increase in the platelet count (median from 229 × 103 to 1020 × 103) had been confirmed. All centrifuge procedures were performed by using an M615E centrifuge device (Elektro mag Lab Aletleri San ve Tic A.Ş., Turkey)
Comparison of perineural platelet-rich plasma and dextrose injections for moderate carpal tunnel syndrome: a prospective randomized, single-blind, head-to-head comparative trial. Shen et al., 201928 The preparation of PRP was performed as previously described (Napolitano et al., 2012; Wu, Ho, Chou, Ke, Li, Huang et al., 2017).Briefly, 10 ml of peripheral venous blood was collected from the vein in the PRP group. The blood was centrifuged at 3400 rpm for 15 min using the universal centrifuge Regen Lab PRP Centri to isolate 3 ml of PRP (RegentKit THT 1, RegenLab SA, Mont sur Lausanne, Switzerland). The RegenKit THT 1 is a leukocyte rich PRP (Dohan Ehrenfest, Rasmusson, & Albrektsson, 2009). Sodium citrate and autologous thrombin were added to promote platelet activation and convert fibrinogen to fibrin.
Carpal Tunnel Syndrome AND Ulnar Neuritis The Effectiveness of Plasma Rich in Growth Factors (PRGF) in the Treatment of Nerve Compression Syndromes of the Upper Extremity: A Retrospective Observational Clinical Study Galán et al., 202235 PRP was elaborated according to PRGF-Endoret technology (BTI Biotechnology Institute, Vitoria, Spain). Briefly, a total of 36 mL of peripheral venous blood was withdrawn into 9-mL tubes containing 3.8 % (w/v) sodium citrate. The blood was centrifuged at 580 g for 8 min at room temperature. The upper volume of the plasma, which contains a similar platelet count to that of peripheral blood (F1), was drawn off and kept in a collection tube to prepare the membrane. The 2-mL plasma fraction (F2), located just above the sediment red blood cells but not including the buffy coat, was collected in another tube and carried to the injection room ready for use. This F2 plasma contained a moderate enrichment of platelets (approximately 2-fold the platelet count of the peripheral blood) with scarce leucocytes. To initiate clotting and platelet activation, calcium chloride (10 % w/v) was added to the liquid F2 just before injection. In order to generate a PRGF membrane, 6–8 mL of the PRGF F1 was activated with calcium chloride (10 % w/v) and incubated at 37 °C for 20–30 min in a glass dish, to allow the formation of a biocompatible fibrin membrane which is then wrapped around the freed-up nerve portion. All the procedures were performed under sterile conditions in the operating room.
Ulnar Neuritis Platelet releasate injection as a novel treatment for ulnar neuritis at the elbow: A case report Bejarano et al., 202334 120 cc of venous blood was aspirated from the antecubital fossa and spun down using a centrifuge to make PRP. Recombinant thrombin (Recothrom) was then added to the PRP and spun down again in the centrifuge. The platelet releasate was subsequently siphoned off, yielding a total volume of 12 mL of platelet releasate solution.
Piriformis Syndrome Effects of ultrasound-guided platelet rich plasma injection in patients with piriformis syndrome Öztürk et al., 202229 T-Lab PRP kit (Bursa, Turkey) was used for the preparation of PRP. A total of approximately 16 ml blood was withdrawn into two tubes. The PRP tubes were centrifuged at 830 G for 5 min using a T-Lab centrifuge with swing rotor. After centrifugation, 2 ml plasma rich in platelets, just above the buffy coat was aspirated from each tube using a manual pipette (total 4 ml).
Common Peroneal Nerve Palsy Ultrasound-guided platelet-rich plasma injections for the treatment of common peroneal nerve palsy associated with multiple ligament injuries of the knee Sánchez et al., 201336 A total of 36 mL of peripheral venous blood was with- drawn into 9-mL tubes containing 3.8 % (wt/vol) sodium citrate. Blood was centrifuged at 580g for 8 min at room temperature (PRGF®-Endoret®, BTI Biotechnology Institute, Vitoria, Spain). The upper volume of plasma, which contains a similar platelet count to that of peripheral blood, was drawn off and discarded in a collection tube. The 2-mL plasma fraction, located just above the sedimented red blood cells, but not including the buffy coat, was collected in another tube and carried to the injection room ready for use. This plasma contains a moderate enrichment in platelets (2- to 3-fold the platelet count of peripheral blood) with scarce leucocytes. To initiate clotting, calcium chloride (10 % wt/vol) was added to the liquid PRGF aliquots just before injection. All procedures were performed under sterile conditions.
2.1

2.1 Statistical analysis

Statistical analysis was only conducted within the CTS studies, given the paucity of literature pertaining to the other forms of neuropathic pain/neuropathies and differences in quantifiable outcome measures. For the analysis of CTS studies, we analyzed the changes in the mean values of the Visual Analog Scale (VAS), Boston Carpal Tunnel Questionnaire Functional Status Scale (FSS), and Boston Carpal Tunnel Questionnaire Symptom Severity Scale (SSS) scores within and between treatment types. The articles included in our meta-analyses only provided summary data (means, standard deviations, number of participants) and had varied patient participation, which prevented paired t-test conduction. Thus, independent t-tests were conducted to determine a statistically significant differences between and within groups. This may result in an overestimation of variability, reduction statistical power, and a potential underestimation of statistical significance. To include all pertinent data, we had to standardize a few values for two studies. The study by Güven et al.19 provided the age and length of symptom duration as mean in months with a minimum and maximum value. Standard deviation was not provided; thus, we assumed a normal distribution and retroactively calculated the standard deviation for these values. All studies that examined BCTQ-FSS and BCTQ-SSS scores provided these values on a scale from one to five except the study by Wu et al.,20 who provided the BCTQ-FSS and BCTQ-SSS scores in their non-averaged form, which is out of 40 and 55 (8 and 11 questions worth 5 points each), respectively. We standardized these values into the format provided by all other studies to assist in analysis. All statistical tests were two-tailed, and a p-value of <0.05 was considered significant.

3

3 Results

The October 2024 PubMed/Medline searches yielded 123 research articles, and, after the two independent reviewers examined these articles, a total of 13 studies that met this inclusion criteria were included. These articles focused on Carpal Tunnel Syndrome (n = 11), Ulnar Neuritis (n = 2), Common Peroneal Neuropathy (n = 1), and Piriformis Syndrome (n = 1). This review included thirteen studies, case series, and case reports, encompassing 509 patients. A meta-analysis was conducted for all articles, but statistical analysis was only conducted on CTS studies, given the paucity of literature pertaining to the other anatomical forms of neuropathic pain/neuropathies.

3.1

3.1 Carpal tunnel syndrome (CTS)19–28

Eleven studies were included in the analysis of the clinical application of PRP for CTS. There were 224 control subjects and 208 experimental subjects, totaling 432 subjects. Control treatments include D5W, saline, and corticosteroid injections, splinting, medical therapy, or carpal tunnel release surgery. Experimental subjects were those that received PRP, as demonstrated. The PRP group was significantly older than the control group (41.38 ± 5.49 and 48.28 ± 6.43 years, respectively, p < 0.001) and had a longer duration of symptoms before clinical intervention (44.38 ± 19.10 and 35.57 ± 15.06 months respectively, p < 0.001). There was no significant difference between the BMI of the two groups.

Visual Analog Scale (VAS), Boston Carpal Tunnel Questionnaire Functional Status Scale (FSS), and Boston Carpal Tunnel Questionnaire Symptom Severity Scale (SSS) scores were collected from these articles. VAS is a validated subjective measure of pain, with scores ranging from zero to ten, with zero being no pain and ten being the worst pain imaginable. FSS and SSS are validated subjective questionnaires which measure the functionality and symptom severity, respectively, in patients with carpal tunnel syndrome that range from one to five. For the FSS test, a score of one means that the patient has no difficulty and a score of five indicates maximum difficulty functioning as a result of CTS. For the SSS test, a score of one means that the patient has little to no symptoms and a score of five indicates maximum symptoms as a result of CTS.

At baseline, there were no significant difference between groups for reported in VAS scores, (p = 0.556)), FSS scores (p = 0.163) or SSS scores (p = 0.394). However, post-treatment the PRP group had significantly lower VAS scores at six months (p < 0.001) (Fig. 1A) and showed significantly greater functionality (higher FSS Scores) (p < 0.001) (Fig. 1B). PRP group also reported significantly lower SSS scores at six months than the control group (p < 0.001), indicating that PRP provided more symptom relief than the summation of all control groups (Fig. 1C).

Outcomes for overall control versus PRP interventions. The symbols used in the figure represent levels of statistical significance. A single asterisk (∗) denotes a p-value less than 0.05 within a group, two asterisks (∗∗) indicate a p-value less than 0.01 within a group, and three asterisks (∗∗∗) signify a p-value less than 0.001 within a group. A tilde (∼) represents a p-value less than 0.05 between respective groups, a caret (^) corresponds to a p-value less than 0.01 between respective groups, and a hash mark (#) indicates a p-value less than 0.001 between respective groups. (a) Comparison of VAS scores for overall control versus PRP interventions. (b) Comparison of FSS scores for overall control versus PRP interventions. (c) Comparison of SSS scores for overall control versus PRP interventions.
Fig. 1 Outcomes for overall control versus PRP interventions. The symbols used in the figure represent levels of statistical significance. A single asterisk (∗) denotes a p-value less than 0.05 within a group, two asterisks (∗∗) indicate a p-value less than 0.01 within a group, and three asterisks (∗∗∗) signify a p-value less than 0.001 within a group. A tilde (∼) represents a p-value less than 0.05 between respective groups, a caret (^) corresponds to a p-value less than 0.01 between respective groups, and a hash mark (#) indicates a p-value less than 0.001 between respective groups. (a) Comparison of VAS scores for overall control versus PRP interventions. (b) Comparison of FSS scores for overall control versus PRP interventions. (c) Comparison of SSS scores for overall control versus PRP interventions.

We further analyzing the efficacy of PRP in comparison to isolated control interventions including D5W and saline injections; corticosteroid injections; non-invasive measures (splinting, medical therapy, etc.); and carpal tunnel release surgery. Prior to intervention, the PRP group had significantly worse reported functionality and symptoms as compared to the D5W and saline injections control group22,27,28 (both p < 0.001). At the end of the treatment follow up, the PRP group reported better functionality and less symptoms compared to these interventions (both p < 0.001). (Fig. 2A and B).

Outcomes for D5W/saline injections versus PRP injections. The symbols used in the figure represent levels of statistical significance. A single asterisk (∗) denotes a p-value less than 0.05 within a group, two asterisks (∗∗) indicate a p-value less than 0.01 within a group, and three asterisks (∗∗∗) signify a p-value less than 0.001 within a group. A tilde (∼) represents a p-value less than 0.05 between respective groups, a caret (^) corresponds to a p-value less than 0.01 between respective groups, and a hash mark (#) indicates a p-value less than 0.001 between respective groups. (a) Comparison of FSS scores for D5W/saline injections versus PRP injections. (b) Comparison of SSS scores for D5W/saline injections versus PRP injections.
Fig. 2 Outcomes for D5W/saline injections versus PRP injections. The symbols used in the figure represent levels of statistical significance. A single asterisk (∗) denotes a p-value less than 0.05 within a group, two asterisks (∗∗) indicate a p-value less than 0.01 within a group, and three asterisks (∗∗∗) signify a p-value less than 0.001 within a group. A tilde (∼) represents a p-value less than 0.05 between respective groups, a caret (^) corresponds to a p-value less than 0.01 between respective groups, and a hash mark (#) indicates a p-value less than 0.001 between respective groups. (a) Comparison of FSS scores for D5W/saline injections versus PRP injections. (b) Comparison of SSS scores for D5W/saline injections versus PRP injections.

Prior to intervention, the PRP group had significantly worse reported pain scores as compared to the methylprednisolone group23 (p < 0.05). At the end of the three-month treatment follow up, the PRP group had significantly less pain in contrast to the methylprednisolone group (p < 0.001)(Fig. 3A). The PRP group also reported significantly better functionality and less symptoms (lower FSS and SSS scores) as compared to the methylprednisolone group throughout the study period (all p < 0.001) and the PRP group had greater reduction in FSS and SSS scores from pre-intervention to the final visit than the methylprednisolone group. (Fig. 3B and C).

Outcomes for steroid injections versus PRP interventions. The symbols used in the figure represent levels of statistical significance. A single asterisk (∗) denotes a p-value less than 0.05 within a group, two asterisks (∗∗) indicate a p-value less than 0.01 within a group, and three asterisks (∗∗∗) signify a p-value less than 0.001 within a group. A tilde (∼) represents a p-value less than 0.05 between respective groups, a caret (^) corresponds to a p-value less than 0.01 between respective groups, and a hash mark (#) indicates a p-value less than 0.001 between respective groups. (a) Comparison of VAS scores for steroid injections versus PRP injections. (b) Comparison of FSS scores for steroid injections versus PRP injections. (c) Comparison of SSS scores for steroid injections versus PRP injections.
Fig. 3 Outcomes for steroid injections versus PRP interventions. The symbols used in the figure represent levels of statistical significance. A single asterisk (∗) denotes a p-value less than 0.05 within a group, two asterisks (∗∗) indicate a p-value less than 0.01 within a group, and three asterisks (∗∗∗) signify a p-value less than 0.001 within a group. A tilde (∼) represents a p-value less than 0.05 between respective groups, a caret (^) corresponds to a p-value less than 0.01 between respective groups, and a hash mark (#) indicates a p-value less than 0.001 between respective groups. (a) Comparison of VAS scores for steroid injections versus PRP injections. (b) Comparison of FSS scores for steroid injections versus PRP injections. (c) Comparison of SSS scores for steroid injections versus PRP injections.

The PRP group had significantly worse reported pain scores, functionality (FSS) and more symptoms (SSS) as compared to the non-operative (medical therapy only) treatment group19,20,24,26 (p < 0.05) prior to any intervention. At the end of the six-month treatment follow up, the PRP group had significantly less pain, better functionality and less symptoms in contrast to non-invasive treatment group (all p < 0.001) (Fig. 4A, B, 4C).

Outcomes for non operative measures versus PRP interventions. The symbols used in the figure represent levels of statistical significance. A single asterisk (∗) denotes a p-value less than 0.05 within a group, two asterisks (∗∗) indicate a p-value less than 0.01 within a group, and three asterisks (∗∗∗) signify a p-value less than 0.001 within a group. A tilde (∼) represents a p-value less than 0.05 between respective groups, a caret (^) corresponds to a p-value less than 0.01 between respective groups, and a hash mark (#) indicates a p-value less than 0.001 between respective groups. (a) Comparison of VAS scores for non operative measures versus PRP injections. (b) Comparison of FSS scores for non operative measures versus PRP injections. (c) Comparison of SSS scores for non operative measures versus PRP injections.
Fig. 4 Outcomes for non operative measures versus PRP interventions. The symbols used in the figure represent levels of statistical significance. A single asterisk (∗) denotes a p-value less than 0.05 within a group, two asterisks (∗∗) indicate a p-value less than 0.01 within a group, and three asterisks (∗∗∗) signify a p-value less than 0.001 within a group. A tilde (∼) represents a p-value less than 0.05 between respective groups, a caret (^) corresponds to a p-value less than 0.01 between respective groups, and a hash mark (#) indicates a p-value less than 0.001 between respective groups. (a) Comparison of VAS scores for non operative measures versus PRP injections. (b) Comparison of FSS scores for non operative measures versus PRP injections. (c) Comparison of SSS scores for non operative measures versus PRP injections.
3.1.1

3.1.1 PRP vs. carpal tunnel release26

Eltabl et al. studied surgical decompression for carpal tunnel syndrome versus ultrasound guided PRP injection. In this study, the surgical intervention group reported significantly worse pain (VAS scores) pre-intervention and at the six month follow up as compared to the PRP group (both p < 0.001). The mean reduction of VAS score was 5.228 for the PRP group and 5.63 for the surgical group (Fig. 5A). Pre-intervention, the PRP group reported significantly better functionality and less symptoms than the surgical group (p < 0.05 and p < 0.001, respectively). However, at six months post-intervention, the surgical decompression group showed greater improvement in function (FSS) and symptom relief (SSS) than the PRP group (Fig. 5B and C).

Outcomes for surgical intervention versus PRP interventions. The symbols used in the figure represent levels of statistical significance. A single asterisk (∗) denotes a p-value less than 0.05 within a group, two asterisks (∗∗) indicate a p-value less than 0.01 within a group, and three asterisks (∗∗∗) signify a p-value less than 0.001 within a group. A tilde (∼) represents a p-value less than 0.05 between respective groups, a caret (^) corresponds to a p-value less than 0.01 between respective groups, and a hash mark (#) indicates a p-value less than 0.001 between respective groups. (a) Comparison of VAS scores for surgical intervention versus PRP injections. (b) Comparison of FSS scores for surgical intervention versus PRP injections. (c) Comparison of SSS scores for surgical intervention versus PRP injections.
Fig. 5 Outcomes for surgical intervention versus PRP interventions. The symbols used in the figure represent levels of statistical significance. A single asterisk (∗) denotes a p-value less than 0.05 within a group, two asterisks (∗∗) indicate a p-value less than 0.01 within a group, and three asterisks (∗∗∗) signify a p-value less than 0.001 within a group. A tilde (∼) represents a p-value less than 0.05 between respective groups, a caret (^) corresponds to a p-value less than 0.01 between respective groups, and a hash mark (#) indicates a p-value less than 0.001 between respective groups. (a) Comparison of VAS scores for surgical intervention versus PRP injections. (b) Comparison of FSS scores for surgical intervention versus PRP injections. (c) Comparison of SSS scores for surgical intervention versus PRP injections.

Piriformis Syndrome29

Piriformis syndrome (PS) is a condition where the sciatic nerve becomes compressed or irritated by the piriformis muscle, causing symptoms of pain, numbness, and/or tingling in the buttock region and radiation down the leg. Diagnosis often relies on clinical history and physical examinations, as the symptoms can closely resemble other conditions, such as herniated lumbar discs. Standard treatments include rest, stretching, NSAIDs, and corticosteroids or botulinum toxin injections. These treatments can be effective but may not work for all patients.30,31 PRP, a therapy known for its anti-inflammatory and regenerative properties, has been widely used for musculoskeletal injuries, though its potential for treating PS remains under-studied.32,33

One study by Öztürk et al. aimed to determine the effects of ultrasound-guided PRP injections on pain and function in patients with PS.29 The study included 60 patients with piriformis syndrome who were randomly divided into two groups to receive either PRP or saline injections under ultrasound guidance. Pain and functional improvements were evaluated over a month using the VAS and Oswestry Disability Index (ODI). The results showed that PRP provided better pain relief and functional improvement than saline during the first week, though the differences between the groups were no longer significant by one-month. The authors suggest that the transient effects of PRP may be due to ongoing trauma or the short half-life of the growth factors in PRP. While the study demonstrates the potential of PRP as a treatment for PS, it highlights the need for further research to explore its long-term efficacy, including larger studies and repeated treatments to better define its role in managing this condition.29

4

4 Ulnar Neuritis34,35

Bejarano et al. describe a case report of a 42-year-old female with right-sided elbow and neck pain that was diagnosed as ulnar neuritis and neurogenic thoracic outlet syndrome. High frequency linear ultrasound at the right elbow demonstrated ulnar neuritis, and initial management included ulnar nerve hydrodissection at the elbow which minimally improved pain. PRP was then injected at the ulnar nerve two weeks following the third hydrodissection. The ulnar nerve entrapment site at Struthers's arcade was identified using a high-frequency linear ultrasound probe in both long and short-axis views. Immediately after the platelet release injection, the patient experienced a noticeable reduction in pain. At the two-week follow-up, the patient reported an initial resolution of symptoms, which subsequently returned to baseline levels within three days of the procedure. By the six-week follow-up, the patient noted an 80 % improvement in elbow pain compared to pre-treatment levels, with continued progress observed. Provocative tests were negative at the elbow, and imaging revealed a normal-appearing ulnar nerve.34

A retrospective review by Galan et al. examined patients who underwent open surgical release of the ulnar epitrochlear ligament followed by Plasma Rich in Growth Factors (PRGF) application. The nerve at the affected site was encased with a pliable membrane-like matrix of F1 PRGF. This intervention demonstrated statistically significant improvements in functional outcomes, as measured by the Quick DASH score, with a median follow-up of 12 months (p < 0.001).35 The limitations of this study include that it was retrospective in nature and had no control arm. Galan et al. suggest that future research should investigate the specific roles of various growth factors in contributing to PRP's neuroprotective, anti-inflammatory, and antifibrotic properties, particularly in the treatment of chronically entrapped nerves.35

4.1

4.1 Common peroneal nerve palsy36

Common peroneal palsy occurs at the fibular head as the common peroneal nerve enters the lateral compartment. It is one of the most common lower extremity compression syndromes. Etiology is multifactorial, but continued compression can lead to pain, dysesthesias of the dorsal foot and eventual weakness of dorsiflexion and eversion.

A case report by Sanchez et al. highlights the potential of PRP, specifically PRGF, as a promising therapeutic option for managing chronic common peroneal nerve palsy. The patient was a 28-year-old male who suffered peroneal nerve palsy with foot drop. After eleven months of minimal recovery, serial intraneural infiltrations of PRGF were performed using ultrasound guidance. The effects were assessed by EMG, echogenicity of peroneal nerve under ultrasound, and manual muscle testing. Over time the patient demonstrated increased muscle strength, partial sensory recovery, and reinnervation confirmed by electromyography. The impact of PRP warrants further investigation, but the application of PRP offers a minimally invasive alternative to traditional surgical options.36

5

5 Discussion

This review demonstrates that PRP injections are associated with statistically significant improvements in pain, functionality, and symptoms of neuropathic pain over time compared to patients who underwent most non-PRP treatments. The study found that in the final follow-up after injection for carpal tunnel syndrome, the PRP group had lower VAS, FSS, and SSS scores than all controls combined, and when control groups were stratified, D5W/saline injection, steroid injection, and splinting/medical management PRP injection had significantly improved scores. However, when compared to surgical intervention of carpal tunnel release, PRP did not prove superior. The use of PRP injections for piriformis syndrome, ulnar neuritis and common peroneal palsy, may be clinically beneficial; however, given the paucity of patients and studies in each group, further research is warranted.34–36

PRP has been shown to be efficacious and cost effective in similar musculoskeletal pathologies including radicular lower back pain, regenerating damaged peripheral nerves, and diabetic peripheral neuropathy.37–39 The authors believe that the use of PRP for peripheral neuropathic pain would likely decreases perineural inflammation and adhesions, thus reducing the resultant pain. PRP, as previously described, is believed to modify inflammation and increase tissue regeneration.40 However, there is little evidence to support optimal timing for PRP treatment. Various formulations of PRP can be created to address specific issues including soft tissue and bone regeneration, stimulation of osteogenesis, angiogenesis, and allowing for cellular migration on the fibrin scaffolding.40 Should PRP be used to augment surgical palliation of peripheral neuropathic pain, it is essential that the formulation, through platelet concentration and total leukocyte differential, be optimized to ensure maximal wound healing and therapeutic benefit. For example, NGF and FGF are crucial for neural healing, thus a formulation that maximizes the cell lines that create them, lymphocytes and platelets, respectively, is essential.

PRP is able to recover damaged tissues through the release of biologic factors, through the promotion of revascularization and synthesis of connective tissue, and has been shown to repair nerves and alleviate nerve-related pain.41 A suggested mechanism of this neural regeneration is that the platelet alpha-granules release fibrinogen, growth factors and tissue proteases and hydrolases.42,43 These, growth factors induce endogenous signaling proteins through the activation of transmembrane receptors on injured cells, inducing gene expression, resulting in collagen synthesis, matrix formation, and cell proliferation.44 A meta-analysis by Wang et al. demonstrates promising basic science, animal models, and clinical improvement in facial, median, and sciatic nerve injuries and transections.41

This review examines the clinical effects of PRP on neuropathic pain across various different anatomic regions. PRP has shown clinical effectiveness and safety for many years in various medical contexts and musculoskeletal diagnoses.45 However, to determine its efficacy in peripheral nerve neuropathies and neuropathic pain, further research is needed to validate the small patients series currently in existence. Large-scale randomized clinical trials where formulations of PRP, patients and outcome measures are standardized are needed. VAS, PROMIS, and other patient and provider-reported functional assessments should be assessed at regular intervals by clinicians caring for these patients.

This review is limited by the potential variability of quality and reliability of the included studies due to biases, small sample sizes, inconsistent methodologies, and lack of access to all original data. Another limitation is the inability to control confounding variables from within the original studies. Furthermore, the heterogeneity of the outcome measures, intervention protocols, and preparation of PRP may limit this study's ability to be generalized.

Based on the current literature, our findings indicate that PRP is an understudied and potentially underutilized treatment method of treatment for peripheral neuropathies. This review has demonstrated that, in the case of carpal tunnel syndrome, PRP injections are the most effective non-surgical option for decreasing patient-reported pain and symptom severity and improving functional status in carpal tunnel syndrome. The promising effects of PRP injections for the treatment of piriformis syndrome, ulnar neuritis and common peroneal palsy are also encouraging.

CRediT authorship contribution statement

Patrick J. Kennedy: conceptualized the study, designed the methodology, conducted a literature review, collected data, performed statistical analysis, led the writing of the manuscript. Shayoni Nag: conducted a literature review, collected data, assisted with writing of the manuscript. Michael Baria: Writing – review & editing, added intellectual content, critically revised the manuscript before submission. Emily Rice: Writing – review & editing. Amy M. Moore: supervised the research process, added intellectual content, critically revised the manuscript before submission.

Statement

Not Applicable. This is a systematic review.

Financial support and sponsorship

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

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