Platelet-Rich Plasma for Postherpetic Neuralgia: Proposed Mechanisms, Clinical Evidence, and Future Research Directions

Abstract

This is a narrative review. A structured literature search was performed across major medical databases to identify relevant pre-clinical and clinical studies investigating PRP for PHN. In total, 10 clinical studies of varied designs were included in this review. Postherpetic neuralgia (PHN) is a refractory neuropathic pain condition characterized by persistent pain lasting more than three months after the resolution of acute herpes zoster. Current pharmacological and interventional treatments primarily focus on symptom modulation, leaving an unmet need for therapies that target the underlying neural damage. As a regenerative therapy with proposed dual mechanisms of anti-inflammatory immunomodulation and potential neural repair, platelet-rich plasma (PRP) delivers high concentrations of growth factors that have been proposed to promote axonal regeneration and Schwann cell activation, while shifting macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, thereby potentially alleviating peripheral and central sensitization. Preliminary clinical observations suggest that PRP monotherapy or PRP combined with pulsed radiofrequency (PRF) may reduce pain intensity, improve sleep quality, and decrease subsequent reliance on gabapentinoids. Combined regimens have been suggested to yield potential synergistic benefits by integrating immediate neuromodulation with hypothesized long-term neural-restorative effects. Current small-scale findings suggest PRP is generally well-tolerated and minimally-invasive for PHN. However, substantial heterogeneity in PRP-preparation protocols and injection methodologies, small sample sizes, geographic concentration of cohorts, active-comparator designs and short follow-up durations across studies limit precise efficacy evaluation. PRP remains investigational for PHN given the absence of direct human evidence for neural repair. Future research should prioritize large‑scale, multicenter randomized controlled trials with extended follow‑up and standardized assessment frameworks to clarify its impact on the natural history of PHN and optimize therapeutic application.

Introduction

Epidemiology and Pathogenesis of Postherpetic Neuralgia

Varicella-zoster virus (VZV) is a ubiquitous, double-stranded DNA alpha herpesvirus that establishes lifelong latency in sensory-ganglion neurons and causes two main human illnesses: primary varicella (chickenpox) and reactivation as herpes zoster (shingles). The disease stages include-Prodromal (pre-rash): Two to three days before the rash, patients typically have fatigue, headache, low-grade fever, and abnormal skin sensations-itching, burning, or prickling; Acute/active: Painful, dermatomal rash appears at the affected dermatome, often leading to marked quality-of-life impairment; and Chronic: About 20% continue to experience pain after the rash resolves, a condition known as postherpetic neuralgia (PHN).¹ PHN is a debilitating neuropathic sequela triggered by the reactivation of the VZV, clinically defined as refractory pain persisting for over three months beyond acute dermatomal rash resolution. The condition manifests as a heterogenous spectrum of chronic pain—typically characterized by continuous burning, paroxysmal lancinating sensations, or electric shock-like stabs—frequently compounded by localized hyperesthesia and tactile allodynia, thereby inflicting a severe, multifaceted impairment on patients’ health-related quality of life (HRQoL).² Moderate-to-severe pain is common among patients living with PHN, frequently producing substantial sleep disturbance. Pain-related sleep disruption in turn contributes to measurable impairments across multiple domains of HRQoL.³

The underlying pathogenesis is driven by intricate, bidirectional crosstalk between peripheral and central nociceptive pathways. Peripheral pathological changes represent well-established consequences of direct viral-mediated insult to primary sensory nerve fibers and dorsal root ganglia (DRG), triggering local release of pro-inflammatory cytokines that maintain peripheral sensitization.^4,5 Central sensitization within the spinal dorsal horn is also well-recognized. By contrast, functional and structural remodeling of supraspinal brain networks represents secondary adaptive change; redundant detailed descriptions of brain network alterations have been condensed. Maladaptive neuroinflammation driven by microglial and astrocytic activation further facilitates pain chronification. We distinguish pathological events occurring during acute viral injury from mechanisms sustaining chronic PHN, and separate human clinical observations from pre-clinical experimental findings. PHN exhibits notable phenotypic heterogeneity among patients.^6–8 The hypothesized relationships between PHN pathological cascades and potential modulatory effects of PRP are illustrated in Figure 1.

Figure 1.

Proposed Effects of PRP in PHN.

Current Status and Limitations of Treatment

Clinical management of PHN typically adheres to a stratified algorithm, prioritizing pharmacotherapy as the foundational strategy, followed by interventional therapies for refractory cases. Established first-line systemic and topical agents encompass tricyclic antidepressants, gabapentinoids (pregabalin and gabapentin), and 5% lidocaine patches. For patients exhibiting an inadequate therapeutic response to initial regimens, secondary options—including serotonin-norepinephrine reuptake inhibitors (eg, duloxetine), 8% capsaicin patches, or tramadol and strong opioids—are escalated to optimize pain control.⁹ Since optimal management frequently necessitates multidrug combinations, a systematic titration protocol is essential. Pharmacotherapy should be initiated at sub-therapeutic doses and incrementally escalated until achieving satisfactory analgesia or encountering dose-limiting toxicities, balancing the efficacy and safety profile of each agent.¹⁰ Interventional modalities span a broad spectrum, ranging from localized infiltrations and peripheral nerve or stellate ganglion blocks to advanced neuraxial interventions and neuromodulation therapies, including transcutaneous/peripheral nerve stimulation, spinal cord stimulation, pulsed radiofrequency (PRF), and dorsal root ganglion ablation. While these targeted techniques offer robust analgesia and functional restoration, inherent procedural risks—such as pneumothorax, hematoma/hemorrhage, and mechanical nerve injury—underscore the critical requirement for operator proficiency and strict anatomical guideline adherence to mitigate complications.¹¹ Compared with conventional thermal radiofrequency ablation, PRF exhibits a superior safety profile, although self-limiting dysesthesia or a paradoxical, temporary exacerbation of the baseline burning sensation within the target dermatome may still occur post-procedure.¹²

Clinical management of PHN follows stratified treatment algorithms based on recent clinical guidelines, which divide interventions into first-line, second-line, and specialist interventional therapies. Treatments for acute herpes zoster pain are distinguished from interventions for established chronic PHN. Conventional therapies produce meaningful clinical benefits for many patients, although they mostly act via symptomatic modulation rather than reversing virus-induced structural nerve injury. Opioids and invasive procedures carry well-documented safety risks and restricted indications. As an interventional approach grounded in regenerative medicine, platelet-rich plasma (PRP) provides abundant reparative factors that have been proposed to facilitate nerve regeneration and repair. PRP is regarded as an experimental adjunct rather than a curative therapy targeting the root etiology of PHN, and it may fill an unmet therapeutic gap that remains to be verified by further evidence.

PRP is an autologous biologic concentrate harvested through the density-gradient centrifugation of whole blood, typically yielding a 2- to 6-fold enrichment in platelet concentration relative to baseline levels. Upon activation, this cellular substrate releases a complex interactome of bioactive molecules; among these, pivotal polypeptide growth factors—including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF)—orchestrate structural tissue regeneration and paracrine signaling cascades.^13,14 Upon degranulation and platelet activation, these mobilized growth factors cooperatively modulate the tissue microenvironment by driving pivotal cellular events—namely proliferation, lineage differentiation, chemotactic migration, and extracellular matrix (ECM) biosynthesis—thereby driving the sequential phases of tissue repair.¹⁵ This specific biochemical composition underpins the multifaceted biological modalities of PRP, delineating its therapeutic potential in structural tissue regeneration.¹⁶ Within the paradigm of regenerative pain medicine, PRP represents a targeted therapeutic strategy capable of facilitating structural tissue restoration and mitigating nociception. This dual mechanistic capacity has driven its clinical translation beyond degenerative arthropathies into refractory neurological disorders.¹⁷ Harnessing this dual neuroregenerative and nociceptive-modulating potential, PRP represents a safe, minimally invasive therapeutic paradigm for the management of refractory neuropathic pain.¹⁸

Despite growing research interest in PRP for PHN, existing published reviews^19–21 mainly summarized overall clinical outcomes, without systematically evaluating study risk-of-bias, PRP preparation heterogeneity, or strictly separating pre-clinical mechanistic inference from human PHN-specific evidence. This narrative review fills this knowledge gap: we critically appraise methodological quality across included studies, systematically analyze PRP product heterogeneity, distinguish pre-clinical hypotheses from clinical observations, and provide multidimensional comparison between PRP and conventional PHN therapies. Nevertheless, current clinical evidence for PRP remains limited, with non-standardized preparation and injection protocols, uncertain injection targets, and absence of direct clinical outcome metrics for neural repair.

Methods

This is a narrative, non-systematic review without formal protocol registration or PRISMA checklist implementation. We searched four electronic databases: PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Data. The search period was limited to publications from database inception to June 2026. Search terms included “postherpetic neuralgia”, “PHN”, “platelet-rich plasma”, “PRP”, “neuropathic pain”, “pulsed radiofrequency”. Eligibility criteria included original clinical studies and relevant preclinical articles investigating PRP for PHN; reviews, case reports and animal studies were included for mechanistic background. Exclusion criteria covered irrelevant topics and duplicate publications. Two authors independently screened titles, abstracts and full-text articles. Duplicates were removed. Extracted data contained study design, sample size, patient characteristics, PRP preparation, interventions, comparators, outcomes and adverse events. Risk-of-bias for each clinical study was narratively assessed.

PRP Biological Characteristics and Analgesic Mechanism

Preparation Systems and Classification

Extracted via density-gradient centrifugation of autologous whole blood, PRP represents a highly concentrated biological substrate. This autologous matrix sequesters a diverse interactome of polypeptide growth factors, immunomodulatory cytokines, and antimicrobial peptides—pivotal among which are PDGF, VEGF, and nerve growth factor (NGF).²²

Current protocols for PRP formulation remain heterogeneous, diverging in anticoagulant selection, centrifugation parameters, and plasma isolation techniques. Standard anticoagulation regimens rely on either sodium citrate or heparin.²³ Centrifugation strategies for PRP formulation primarily comprise two paradigms: the double-spin and single-spin protocols. The double-spin technique utilizes an initial low-speed centrifugation step to sediment erythrocytes, followed by a high-speed cycle to concentrate platelets. Conversely, the single-spin method achieves concentration via a solitary centrifugation process, which offers superior procedural simplicity, accelerated preparation speed, and cost-effectiveness. Available literature does not definitively establish that the double-spin paradigm yields superior platelet enrichment efficiency, sterility, or reduced cross-contamination risk compared with single-spin approaches; these two represent alternative practical preparation workflows.^16,23,24

We explicitly distinguish PRP from platelet-rich fibrin (PRF). Furthermore, dictated by variations in fibrin architecture alongside leukocyte and platelet profiles, PRP is systematically categorized into four primary cohorts: leukocyte- and platelet-rich fibrin (L-PRF), pure platelet-rich fibrin (P-PRF), pure platelet-rich plasma (P-PRP), and leukocyte- and platelet-rich plasma (L-PRP). This taxonomic framework transcends the mere quantification of absolute platelet counts and enrichment factors; it concurrently incorporates the extent of leukocyte infiltration and the structural density of the three-dimensional fibrin scaffold. Consequently, this system precisely maps the divergent biological signatures of these subcategories regarding growth factor release kinetics, immunomodulatory dynamics, antimicrobial efficacy, and mechanical tissue-support capacity.^25,26 Characterized by dense leukocyte profiles, L-PRF and L-PRP secrete elevated concentrations of immunomodulatory factors and antimicrobial peptides, rendering them suitable for pathological microenvironments vulnerable to infection or requiring targeted immune modulation. Conversely, P-PRF and P-PRP, featuring minimal leukocyte presence, minimize pro-inflammatory background signaling, which may favor scenarios prioritizing isolated neural regeneration or angiogenesis. Structurally, the dense fibrin architecture within the PRF cohort serves as a biological scaffold that orchestrates the sustained release of paracrine signals. In contrast, the fluid state of the PRP cohort facilitates high-precision, ultrasound-guided infiltration and seamless integration with complementary biomaterials. This taxonomic framework informs the selection of specific subtypes for PHN interventions and guides the refinement of delivery techniques.^27–29 As an autologous biological product, PRP offers safety advantages by minimizing risks of cross-contamination, disease transmission, and immune-related adverse reactions.³⁰ Future PHN-focused studies are encouraged to adopt established PRP reporting standards to improve cross-study comparability.

Given substantial inter-study heterogeneity in PRP product profiles, injection modalities and enrolled patient phenotypes, future PHN-focused interventional trials are strongly encouraged to adhere to internationally-recognized PRP reporting standards. Complete documentation of platelet enrichment magnitude, leukocyte composition, activation approaches, centrifugation parameters, injection volume, target site, treatment interval and total number of sessions will facilitate cross-study comparison and improve research reproducibility.

Key Growth Factors

PRP exerts biological effects via supra-physiological concentrations of growth factors—principally PDGF, TGF-β, VEGF, and insulin-like growth factor-1 (IGF-1), which have been demonstrated mainly in pre-clinical models—that may regulate inflammation, cellular proliferation, and tissue remodeling through paracrine signaling. Specifically, PDGF may recruit mesenchymal stem cells and stimulate fibroblast proliferation, while TGF-β may induce collagen deposition and chondrogenic differentiation. Concurrently, VEGF may promote angiogenesis, and IGF-1 may accelerate extracellular matrix (ECM) maturation. In parallel, serotonin released upon platelet degranulation has been suggested to produce rapid analgesia by downregulating nociceptor excitability.¹⁷ The leukocyte components within PRP may exert bidirectional immunomodulation: neutrophils clear pathogens via neutrophil extracellular traps (NETs), whereas monocytes may polarize into anti-inflammatory M2 macrophages to secrete IL-10 and TGF-β1, thereby potentially dampening chronic inflammation and fibrosis. Mechanically, the three-dimensional fibrin scaffold can act as a structural matrix for cell migration and a reservoir for sustained growth-factor release; it may transduce biophysical signals enhancing crosstalk between endothelial cells and fibro-adipogenic progenitors (FAPs). This cascade could activate satellite cells, support myogenic differentiation, and contribute to formation of microvascular networks.^31–34 Critically, a negative feedback loop involves platelet-derived factors that blunt excessive TGF-β/Smad3 activation, thereby mitigating aberrant collagen deposition.³⁵ Most above-mentioned mechanistic findings come from pre-clinical studies rather than direct human PHN data. PRP therefore possesses proposed pro-regenerative, anti-fibrotic and analgesic properties; however, it cannot be regarded as an established disease-modifying therapy for neuropathic pain.

PRP and Neuro-Immune Crosstalk

A core proposed property of PRP is its potential to function as a bio-signal modulator that remodels the local neuro-immune microenvironment, as mainly observed in pre-clinical experiments. Upon degranulation, PRP-derived molecular cargo including growth factors, cytokines, and exosomes may act on infiltrating immune cells as well as resident neural components such as Schwann cells, neurons, and satellite glial cells. This signaling cascade has been proposed to drive macrophage polarization toward the M2 phenotype, promote a T-helper cell type 2 (Th2) immune shift, and suppress aberrant spinal microglial activation. Increased anti-inflammatory mediators such as IL-10 and TGF-β1 may support neural-related recovery and axonal regeneration, potentially forming feedback loops that interfere with the “inflammation-pain-neurodegeneration” vicious cycle. Mechanistically, factors including TGF-β, PDGF and specialized pro-resolving lipid mediators are hypothesized to induce reparative M2-type monocyte-macrophage polarization. M2-like macrophages may clear apoptotic debris and secrete IL-10 and neurotrophic factors, which could improve the microenvironment for axonal regrowth. Furthermore, PRP may modulate adaptive immunity by shifting responses toward Th2 and restraining pro-inflammatory Th1/Th17 pathways, which might reduce immune-mediated neural injury after virus infection. All these neuro-immune interactions remain largely hypothetical for human PHN patients and require further clinical verification.^36,37

Modulation of Peripheral and Spinal Nociceptive Pathways

Beyond its proposed reparative and anti-inflammatory properties, PRP may exert neuromodulatory influences on nociceptive pathways, as mainly suggested by pre-clinical findings. This mechanism is hypothesized to operate by gating aberrant peripheral nociceptor excitability and tuning synaptic transmission efficiency within the spinal dorsal horn. This hypothesis converges with the contemporary paradigm of neuropathic pain, wherein the maintenance of central sensitization hinges upon an intricate interplay between neurons and glial subsets—principally microglia and astrocytes, which serve as pivotal drivers of pain-signal amplification.³⁸ PRP is proposed to produce multi-pathway synergistic effects, bidirectionally modulating immune responses to interfere with the inflammatory-pain vicious cycle. Through growth factors and extracellular vesicles, PRP may activate Schwann cells and support axonal regrowth, potentially improving epidermal nerve-fiber density and mitigating peripheral as well as central sensitization. This multi-target concept originates largely from pre-clinical data. Symptom improvement in patients could also arise purely from local immunomodulatory effects rather than actual neural regeneration. It should be explicitly emphasized that there is currently no direct human clinical evidence demonstrating structural neural repair in PHN patients receiving PRP. Collectively, these pre-clinical findings outline several plausible pathways by which PRP may alleviate PHN-related pain. A schematic overview of these hypothesized mechanisms is provided in Figure 2.

Figure 2.

Schematic diagram illustrating the potential mechanisms by which PRP relieves post- herpetic- neuralgia.

Notes: Cross- marks denote the inhibitory effect of PRP on pathological neural sensitization and inflammation- pain- damage loop.

Advances in Clinical Application Research

Detailed baseline characteristics, intervention parameters and risk-of-bias evaluations for all ten included clinical studies are presented in Tables 1 and 2.

Table 1.

Characteristics of Included Clinical Studies of PRP Monotherapy for Postherpetic Neuralgia

Author/Year	Sample Size	Study Design	Intervention & Comparator	Injection Site	PRP Preparation	Follow-Up Duration	Key Outcome Data	Adverse Events	Risk-of-Bias Assessment
Mohammed AbuEl-Hamd/202439	45	Single-arm trial (SAT)	I: autologous intralesional PRP injection; No control group	Intralesional	Reported: 1000 rpm, 10 min; ×g conversion not feasible because rotor-radius data were not provided in the original publication	3 months	VAS, NRS, VRS, SF-36 scores decreased from baseline	Not reported	High risk of bias: single-arm, no sham/placebo control, small sample.
Feng M-X/202340	40	RCT	I: autologous PRP injection (monotherapy); C: systemic pharmacotherapy (drugs only)	Intralesional	Reported: 1500 rpm, 10 min; ×g conversion not feasible because rotor-radius data were not provided in the original publication	3 months	No obvious changes in pain-related and quality-of-life metrics were observed at 7-day follow-up; reductions in VAS, NRS, VRS and improvements in SF-36 from baseline were noted at 3-month follow-up in the PRP group.	Not reported	Risk of bias: active-comparator design, no placebo or sham-control arm. Skin-temperature difference is treated as an exploratory physiological outcome.

Table 2.

Summary of Included Clinical Studies of PRP Combined Therapy for Postherpetic Neuralgia

Author/Year	Sample Size	Study Design	Intervention & Comparator	Injection Site	PRP Preparation	Follow-Up Duration	Key Outcome Data	Adverse Events	Risk-of-Bias Assessment
Huang L-R/202141	30	RCT	I: PRP + systemic pharmacotherapy; C: systemic pharmacotherapy alone	Intralesional	Reported: 1500 rpm, 10 min; 2500 rpm, 10 min; ×g conversion not feasible because rotor-radius data were not provided in the original publication	1 month	SF-MPQ (PRI, VAS, PPI) scores reduced versus baseline; pregabalin dosage was decreased in intervention group.	Not reported	Risk of bias: active-control design, no placebo control.
Yuan L-G/202242	52	RCT	I: PRF + PRP; C: PRF + placebo	Intralesional	Reported: 2500 rpm, 15–20 min; ×g conversion not feasible because rotor-radius data were not provided in the original publication	3 months	VAS and PSQI decreased in both groups; greater magnitude of reduction observed in E group at 2, 4, 8, 12-week time-points.	Not reported	Risk of bias: active comparator, absence of true placebo.
Zhang M-H/202543	60	RCT	I: PRF + PRP; C: PRF + ozone	Intralesional	Reported: 4000 rpm, 10 min; ×g conversion not feasible because rotor-radius data were not provided in the original publication	6 months	VAS, PSQI decreased in both groups; lower VAS and PSQI values were observed in PRP group across post-treatment time-points including 6-month follow-up.	Not reported	Risk of bias: active-comparator design, no placebo arm.
Wu G/202344	79	RCT	I: PRF + PRP; C: PRF	Intralesional	Reported: 1500 rpm, 10 min; 3200 rpm, 8 min; ×g conversion not feasible because rotor-radius data were not provided in the original publication	1 week	Total effective rate: study group 92.31% vs control 71.79% (P<0.05). Baseline pain-inflammatory mediators and PSQI were similar between groups (P>0.05). At 1-week follow-up, the study group had lower 5-HT, MCP-1, PGE2, CRP, IL-6 and lower PSQI (P<0.05).	Study group: 1 local infection, 1 skin rash; Control group: 1 local infection. No significant between-group difference in adverse-event rate (5.13% vs 2.56%, χ2 = 0.000, P = 1.000).	Risk of bias: random-number-table randomization; allocation concealment not described; no blinding performed; active-control design without placebo; limited sample size.
Kang B-W/202345	60	RCT	I: PRF + PRP; C: PRF + drugs	Intralesional	Reported: 3300 rpm, 4 min; 3500 rpm, 5 min; ×g conversion not feasible because rotor-radius data were not provided in the original publication	3 months	Both groups showed improved VAS, PSQI and ∆T at 1 d, 2-week, 4-week and 3-month follow-ups vs baseline (all P<0.05). At 3 months, the PRP group had lower VAS and PSQI than the glucocorticoid group (P<0.05). PRP group exhibited lower ∆T across all time-points (all P<0.05). No severe adverse events occurred.	Not reported	Risk of bias: Random-number-table randomization; allocation concealment not described; no blinding performed; active-control design without placebo; limited sample size.
Tang G-S/202346	106	RCT	I:RFT + PRP injection. C: RFT alone.	Intralesional	Reported: 3200 rpm, 8 min; ×g conversion not feasible because rotor-radius data were not provided in the original publication	8 weeks	Observation group achieved significantly lower VAS at 4 weeks, PSQI at 2- and 8-weeks, HAMD at 2-, 4- and 8-weeks, and DLQI at 8 weeks compared with controls (all P<0.05).	Not reported
Hu M-L/202547	60	RCT	I:PRP + sympathetic/paravertebral block (SB); C: PRF monotherapy	Intralesional	Reported: 1450 rpm, 10 min; 1800 rpm, 10 min; ×g conversion not feasible because rotor-radius data were not provided in the original publication	6 months	Lower VAS, PSQI, HAMD, HAMA scores were observed in group E relative to group C.	Not reported	Risk of bias: different co-interventions between two arms, cannot isolate PRP-specific effect.
Zhu R-R/202448	60	RCT	I: Ultrasound-guided paravertebral nerve block combined with PRP injection; C: Ultrasound-guided paravertebral nerve block alone	Intralesional	Not reported	8 weeks	VAS, PSQI and DLQI scores decreased at T1-T5 compared with T0 in both groups; lower VAS, PSQI and DLQI values were observed in the experimental group versus the control group at all time-points (P<0.05).	Control group: 2 cases of nausea and vomiting, 3 cases of dizziness, 2 cases of drowsiness, 1 case of skin swelling, adverse-event rate 26.6% (8/30); Experimental group: 1 case of dizziness, 1 case of drowsiness, adverse-event rate 6.6% (2/30). Inter-group difference in adverse-event rates was statistically significant (χ2 = 4.320, P<0.05).	Risk of bias: active-comparator design, no placebo-control arm. Cannot fully separate the effect of PRP from paravertebral block.

Notes: Where original papers only reported rotational speed (rpm), conversion to relative centrifugal force (×g) was not feasible due to missing rotor-radius data; original rpm values are retained for trace.

PRP Monotherapy Injection

PRP infiltration as a standalone intervention delivers concentrated humoral factors to sites of neural injury, with the aim of modulating nociceptive signaling and supporting tissue repair. Clinical deployment primarily centers on dermatomal subcutaneous or targeted intralesional injections. In a prospective cohort (n=45), biweekly dermatomal injections of autologous PRP (four sessions total according to affected sensory segments) were associated with reductions in Visual Analog Scale (VAS) and numerical rating scale (NRS) scores, as well as improvements in Short-Form-36 (SF-36) quality-of-life metrics at 3-month follow-up.³⁹

Observations from a randomized active-control trial (n=40) in refractory upper-thoracic PHN compared intradermal autologous PRP (8 mL) versus a conventional multimodal block (2 mL mecobalamin + 1 mL compound betamethasone + 5 mL lidocaine), administered every 3 days for two sessions. Relative improvements in analgesia and functional outcomes were observed in the PRP group. Localized skin-temperature elevation within the affected dermatome was noted among PRP-treated participants; however, this represents an exploratory physiological finding, and it cannot be interpreted as definitive evidence for reversal of sympathetic-mediated ischemic pain.⁴⁰ It should be emphasized that available monotherapy evidence is limited by small sample sizes, absence of placebo or sham-control arms, and potential for spontaneous symptom improvement over the natural clinical course of PHN. Risk-of-bias assessments for these monotherapy studies are summarized in Table 1.

PRP Co-Administration with Pharmacotherapy

Combining PRP with systemic analgesics has been explored as one potential strategy to improve symptom control and reduce analgesic exposure. One small cohort included PHN patients with concomitant myofascial trigger points (n=30) receiving ultrasound-guided intralesional PRP infiltration. Changes across multiple pain-related indices (PRI, VAS, PPI, SF-MPQ) and pregabalin dose tapering were reported following intervention.⁴¹ Patients presenting with myofascial trigger points may constitute a distinct clinical subgroup, and findings from this subset may not generalize to the broader PHN population. It is worth noting that this original report did not provide full baseline pregabalin doses, standardized tapering criteria, or dedicated neurocognitive outcome assessments. Reduction in pregabalin dosage cannot be directly inferred as evidence of reduced neurocognitive side effects. Study details and risk-of-bias rating are provided in Table 2.

PRP Interfaced with Neuromodulation

Combining PRP with neuromodulatory interventions is an investigational approach built on the hypothesis that neuromodulation may suppress aberrant nociceptive activity and create a more permissive local microenvironment for tissue repair. Subsequent or concurrent PRP infiltration delivers concentrated biological mediators that are hypothesized to support neural-related repair; however, it remains difficult to disentangle the independent therapeutic contribution of PRP from effects produced by the neuromodulatory procedure itself.

Synergy with Pulsed Radiofrequency

The combination of PRP with PRF represents the most thoroughly investigated hybrid regimen to date. Mechanistically, PRF induces a low-energy electromagnetic field that temporarily halts the propagation of ectopic impulses along demyelinated axons without causing structural destruction, thereby creating a metabolic window for the tissue-engineered repair mediated by subsequent PRP deposition.

PRF generates low-energy electromagnetic fields to suppress ectopic neuronal discharges without overt structural nerve injury, which has been hypothesized to provide a favorable microenvironment for subsequent PRP application. Multiple clinical studies have compared PRF monotherapy versus PRF combined with PRP. Between-group differences in analgesia, sleep metrics, and rescue-analgesic requirements have been reported across these active-comparator studies.^42–45 Observed changes in circulating pro-inflammatory or nociceptive biomarkers cannot be taken as direct evidence of neural regeneration. Although some studies reported more favorable long-term pain trajectories in the PRP-plus-PRF arms, these findings should be interpreted cautiously given study limitations including non-placebo control designs. Full procedural parameters and risk-of-bias evaluations for these trials are compiled in Table 2.

Combination with Radiofrequency Thermocoagulation

Radiofrequency thermocoagulation (RFT) represents a neurodestructive intervention. One retrospective observational study compared CT-guided interforaminal RFT combined with PRP versus RFT alone for refractory upper-thoracic PHN.⁴⁶ Statistical between-group differences in VAS, PSQI, HAMD and DLQI were reported across follow-up time-points. As this work is retrospective, selection bias cannot be excluded; patient baseline characteristics may have differed systematically between groups, which limits causal inference regarding added benefit from PRP. The claim that PRP mitigates deafferentation-related pain cannot be firmly concluded from this single retrospective dataset. Risk-of-bias assessment is available in Table 2.

Interface with Nerve Blocks

PRP has been combined with regional nerve blocks under the hypothesis that temporary conduction block may be paired with potential tissue-repair-related effects of PRP. One controlled study (n=60) compared transforaminal PRP plus sympathetic block versus PRF monotherapy, reporting group-level differences in pain outcomes, mood metrics, and analgesic discontinuation rates.⁴⁷ Another ultrasound-guided paravertebral-block trial compared nerve-block monotherapy versus block plus PRP, documenting inter-group differences in VAS, PSQI and DLQI across follow-up visits.⁴⁸ Because both arms received active interventional treatment, it is challenging to attribute observed outcome differences exclusively to PRP. Because both arms received active interventional treatment, it is challenging to attribute observed outcome differences exclusively to PRP. Furthermore, these included studies exhibited substantial heterogeneity in procedural details, including inconsistent anesthetic types, application of glucocorticoids, variable injection volumes and treated spinal segments, diverse imaging guidance modalities, and discrepant treatment frequencies. Such inconsistent adjunctive interventions and operational parameters inevitably introduce confounding effects and interfere with the authenticity and specificity of curative effect evaluation. Therefore, the superior clinical efficacy observed in combined treatment groups cannot be entirely attributed to the biological repair function of PRP alone. Corresponding study information and risk-of-bias ratings are summarized in Table 2.

Tolerability and Safety Profile

As an autologous biological product, PRP reduces risks related to allogeneic material such as graft-versus-host responses and exogenous pathogen transmission; nevertheless, it is not entirely free of risk. Potential hazards include risks arising from blood processing and centrifugation, as well as procedure-related complications such as injection-site pain, bleeding, local infection, or reactions to anticoagulants used during PRP preparation. There is no clear evidence that PRP directly alters hepatic or renal drug-metabolizing pathways.

Available trial data suggest that most reported adverse events following PRP for PHN are transient mild local reactions including soreness and erythema; severe systemic or procedural complications have rarely been described in published small cohorts. In one paravertebral-block trial (n=60), a lower adverse-event proportion was observed in the block-plus-PRP arm (6.6% [2/30]) relative to the block-only arm (26.6% [8/30]; χ² = 4.320, P < 0.05).⁴⁸ This single-study observation cannot establish that PRP itself improves overall safety; group differences may be influenced by baseline patient characteristics, adverse-event ascertainment bias, or other confounding factors. Adverse-event summaries from each included study are collated within Table 1 and Table 2.

Evidence Synthesis and Future Perspectives

Current published studies, most of which originate from Chinese clinical centers, report variable degrees of symptom improvement after PRP-related interventions for PHN. This geographic concentration of available studies raises potential concerns regarding publication bias and limits generalizability to other patient populations. Multiple small-sized studies reporting positive outcomes do not constitute high-certainty clinical evidence. Underlying hypothesized mechanisms include modulation of neuroinflammation and microenvironment remodeling; however, direct human evidence confirming PRP-driven axonal regeneration in PHN patients remains absent.

Discussion

Pre-clinical work has described anti-inflammatory and tissue-repair-associated bioactivity of PRP; however, direct human clinical evidence confirming neural repair after PRP treatment for PHN is currently absent. Observations from published clinical cohorts and active-control trials suggest PRP-related interventions may be associated with pain relief and improvements in patient-reported sleep and quality-of-life outcomes in some people living with PHN. These observed benefits must be interpreted cautiously given important study limitations.

Substantial methodological heterogeneity exists across the included literature and hinders direct cross-study comparison. Variability in whole-blood input volume, centrifugation parameters, platelet activation approaches, and processing conditions alter final PRP composition and leukocyte content.^49,50 At present, no consensus has been reached regarding optimal injection volume (1–5 mL), treatment interval (1–4 weeks), or total number of sessions (1–4). Well-designed head-to-head comparative studies addressing these practical parameters remain limited.⁵⁰

Most of the available clinical data originate from Chinese study cohorts. This geographic concentration raises concerns about potential publication bias and restricts how broadly these findings can be generalized to patient populations in other regions. Study follow-up periods are often short, and trials apply inconsistent pain and functional outcome tools, including VAS, NRS, FPS-R, as well as sleep, mood and quality-of-life questionnaires (SF-36, PSQI, HAMD, DLQI). Such heterogeneity precludes formal meta-analysis and increases the risk of outcome-reporting bias.^51,52

Some patient subgroups may show differential treatment responses. Patients with relatively short PHN duration, preserved peripheral nociceptor function, and absence of major comorbidities such as diabetes may theoretically derive greater benefit; these subgroup hypotheses remain exploratory and require prospective validation in adequately powered trials.

Given the low overall certainty of existing evidence, PRP cannot be recommended as routine standard-of-care for PHN. We further compared PRP against conventional established interventions for PHN in textual form across key clinical dimensions, including analgesic efficacy, durability of benefit, cost-burden, clinical accessibility, procedural demands, adverse-event risk, overall evidence certainty, and requirement for specialized staff or imaging guidance. Conventional pharmacotherapy (gabapentinoids, tricyclic antidepressants, topical agents) represents first-line therapy with broad accessibility and low procedural risk, yet provides predominantly symptomatic relief without targeting neural injury. Neuromodulatory approaches such as pulsed-radiofrequency or nerve-block interventions can achieve sustained pain relief for refractory PHN but require interventional expertise and imaging guidance and carry inherent procedural risks. By comparison, PRP is an experimental regenerative-oriented interventional modality; it may deliver potential neural-modulating benefits, but it is associated with higher direct costs, limited real-world accessibility, heavy reliance on specialized procedural skills, and low overall certainty of evidence, given small sample sizes and heterogeneous study protocols among available investigations.

Of note, pre-clinical investigations have also highlighted potential therapeutic roles of PRP-derived exosomes and stem-cell-associated crosstalk, although relevant human clinical data specific to PHN are currently absent. Accumulating evidence indicates that a substantial fraction of PRP efficacy is mediated by its rich reservoir of extracellular vesicles, particularly platelet-derived exosomes (PRP-Exos). These nanoscale vesicles encapsulate complex bioactive cargo—including proteins, mRNAs, and microRNAs—thereby serving as vital vectors for intercellular communication. Illustratively, Zhang et al⁵³ documented that PRP-Exos activate pro-survival and neuroregenerative signaling cascades—specifically phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)—within recipient cells via the horizontal transfer of specific miRNAs, including miR-21-5p and miR-223-3p. Critically, PRP-Exos serve as a priming stimulus to pre-condition mesenchymal stem cells (MSCs), markedly enhancing their homing efficiency, paracrine potency, and differentiation potential into neuron-like lineages. This cellular crosstalk yields a synergistic neurorestorative cascade that far surpasses the therapeutic efficacy of either independent modality. PRP-stem-cell combinations should not be portrayed as currently available treatments for PHN.

Improved adherence to established PRP reporting standards is needed to reduce heterogeneity in future publications. Large-sample, multicenter, placebo-controlled randomized trials with extended follow-up are required to clarify long-term efficacy and safety profiles. While combined interventional-PRP approaches are conceptually appealing, high-quality evidence confirming true synergistic effects is currently lacking.

Conclusion

Preliminary clinical data from small non-controlled and active-comparator studies indicate that PRP monotherapy or combined neuromodulation may alleviate pain and improve sleep and quality of life in certain PHN patients. Variations in pain reduction magnitudes and clinical responder rates exist across studies. Significant methodological heterogeneity precluded quantitative data pooling in this review, and current clinical improvements should be interpreted cautiously.

Overall, the certainty of existing evidence is low. The hypothesized neural repair effects of PRP are primarily derived from pre-clinical observations, while direct clinical evidence of human neural regeneration remains absent.

Clinically, PRP should be considered an experimental adjunct rather than a standard treatment for PHN. It may be selectively applied for patients with insufficient response or intolerance to first-line therapies after thorough shared decision-making. Patients must be fully informed of limited clinical evidence, procedural risks, and alternative evidence-based treatments. Where feasible, PRP administration is recommended within formal clinical research settings.

Future high-quality, multicenter, placebo-controlled randomized trials with standardized PRP preparation protocols, unified outcome measures and extended follow-up are essential to clarify the real-world efficacy, safety and optimal patient selection criteria for PHN treatment.

Disclosure

The authors report no conflicts of interest.