Ultrasound-Guided Zhengqing Fengtongning vs Corticosteroid Injections for Plantar Fasciitis: A Randomized Controlled Trial on Short- and Long-Term Efficacy

Introduction

Plantar fasciitis, a leading cause of chronic heel pain in adults, is characterized by severe pain during the first steps in the morning or after prolonged standing, with recurrent episodes often compromising quality of life and functional mobility [1–3]. Current clinical practice follows a stepwise treatment approach, prioritizing non-surgical interventions such as rest, non-steroidal anti-inflammatory drugs (NSAIDs), physical therapies (stretching, extracorporeal shock wave therapy), and orthotic devices [4–7]. While these approaches provide short-term relief for 70% to 80% of patients, 20% to 30% of refractory cases require advanced interventions [2].

Corticosteroid injections are the first-line injectable therapy due to their rapid anti-inflammatory effects, particularly for acute exacerbations unresponsive to non-invasive treatments [8–10]. However, their clinical utility has been limited by significant long-term risks: systematic reviews have shown that single injections provide analgesia for 6 weeks, but repeated administrations can induce plantar fascia matrix degradation, increasing the risk of structural injuries such as fat pad atrophy and full-thickness tears [3,11].

Zhengqing Fengtongning, a modern extract of the Chinese herb Sinomenium acutum, contains sinomenine hydrochloride as its active component, offering multi-target therapeutic advantages: it suppresses pro-inflammatory cytokines (TNF-α, IL-6) via NF-κB pathway inhibition while activating μ-opioid receptors for central analgesia [12,13]. In musculoskeletal conditions like rheumatoid arthritis and knee osteoarthritis, Zhengqing Fengtongning injections have demonstrated significant improvements in pain scores and joint function, with a lower adverse event rate compared to corticosteroids [14,15]. Despite growing clinical use in plantar fasciitis, evidence remains scarce, primarily consisting of case reports or small observational studies lacking direct comparisons with corticosteroids and long-term follow-up data.

Against this backdrop, this study employs ultrasound-guided precision targeting and a randomized controlled trial (RCT) design to compare Zhengqing Fengtongning and corticosteroid injections for chronic plantar fasciitis, aiming to evaluate short-term analgesic equivalence and long-term functional outcomes, thereby informing safer and more effective injection therapies.

Material and Methods

PARTICIPANTS:

Patients with plantar fasciitis were recruited from the Department of Rehabilitation Medicine and the outpatient clinic of Qingdao No. 8 People’s Hospital (August 2022 to August 2023). The inclusion criteria were as follows: 1) patients met the clinical diagnostic criteria for plantar fasciitis, as defined by clinical assessment in accordance with established guidelines [16]; 2) age ranged from 30 to 65 years; 3) body mass index (BMI) was between 22 and 29 kg/m2; 4) disease duration was 3 to 12 months, with no prior corticosteroid therapy during this period. Exclusion criteria included: 1) history of ankle/foot fractures or structural foot abnormalities; 2) signs of soft-tissue infection (eg, erythema, swelling) at the heel or bleeding tendencies; 3) concomitant hemorrhagic disorders, use of anticoagulant medications, or history of mental illness; 4) contraindications to injections of corticosteroids, lidocaine, or Zhengqing Fengtongning. The study protocol was reviewed and approved by the Medical Ethics Committee of Qingdao No. 8 People’s Hospital (QBYLL-KY-2022-051), and all participants provided written informed consent prior to study initiation.

A total of 80 patients were initially screened for enrollment, among whom 26 were excluded: 6 declined participation, 17 failed to meet inclusion criteria, and 3 had their injections canceled due to procedural contraindications. This left 54 eligible patients who were subsequently enrolled. Randomization was performed using a random number table method. Sequences were generated by an independent statistician (unrelated to recruitment) using the random number table and allocated at a 1: 1 ratio (odd numbers for the observation group, even numbers for the control group). The CONSORT flow diagram detailing participant recruitment and allocation is presented in Figure 1. All 54 patients completed the 3-month follow-up, with no dropouts. Thus, the full analysis set was used. There were no statistically significant differences in baseline characteristics such as age, disease duration, or body mass index (BMI) between the 2 groups (P>0.05) (Table 1).

INTERVENTION PROTOCOLS:

Observation Group: Patients received ultrasound-guided focal injections of Zhengqing Fengtongning (Hunan Zhengqing Pharmaceutical Group Co., Ltd., China; State Drug Administration Approval No. Z43020279; specification: 2 mL: 50 mg). The procedure was performed using a Clover50 portable ultrasound system (Shenzhen, China) with a 10-MHz high-frequency linear probe. After skin disinfection of the injection site, the painful area of the plantar fascia was localized via ultrasound guidance. A mixture of 1 mL Zhengqing Fengtongning, 0.5 mL 2% lidocaine hydrochloride injection, and 1 mL 0.9% sodium chloride injection was administered via needle puncture. Treatments were delivered once daily for 5 days per week, totaling 10 injections. Control Group: Patients underwent ultrasound-guided corticosteroid injections using Compound Betamethasone (Diprospan, Schering-Plough Shanghai Pharmaceutical Co., Ltd., China; 1 mL containing 5 mg betamethasone dipropionate and 2 mg betamethasone sodium phosphate). Following skin disinfection and ultrasound-guided localization of the painful fascia, a mixture of 1 mL Diprospan, 0.5 mL 2% lidocaine hydrochloride, and 1 mL 0.9% sodium chloride was injected. Treatments were administered once weekly for 2 weeks, totaling 2 injections. All injections were performed by a single experienced clinician. After each session, both groups received a 10-minute cold compress and identical standardized stretching therapy. Patients were advised to avoid direct pressure on the injection site for 48 hours after treatment.

OUTCOME ASSESSMENTS:

Patients in both groups underwent the Visual Analogue Scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) scoring, and plantar fascia thickness measurements at baseline, 1 week, 1 month, and 3 months post-treatment. Pain intensity was evaluated using VAS. Foot function was assessed with the Ankle-Hindfoot Scale recommended by the AOFAS [17]. This scale comprises 9 domains: pain, functional and self-care ability, support capacity, maximum walking distance, gait, anterior-posterior mobility (flexion-extension), hindfoot mobility (inversion-eversion), ankle-hindfoot stability (anterior-posterior and inversion-eversion), and foot alignment. The total score ranges from 0 to 100, categorized as: excellent (90–100), good (75–89), fair (50–74), and poor (<50). Plantar fascia thickness was measured via musculoskeletal ultrasound. Patients were positioned prone with the ankle in neutral alignment. A high-frequency linear probe was applied perpendicularly to the plantar surface of the heel, and thickness was measured at 5 mm distal to the medial calcaneal tubercle. The average of 2 measurements was recorded as the final result.

STATISTICAL ANALYSIS:

Data analysis was performed using SPSS 29.0 statistical software. The Shapiro-Wilk method was used to test the normality of the data. Measurement data conforming to the normal distribution were expressed as mean±standard deviation, and count data were compared using the chi-square test. Measurement data at multiple time points were analyzed by repeated-measures analysis of variance. One-way analysis of variance was used for inter-group comparisons, and the least significant difference (LSD) method was used for post hoc pairwise comparisons. Paired t test was used for intra-group comparisons. The statistical significance level was set at P<0.05.

Results

PAIN INTENSITY:

Before treatment, there was no statistically significant difference in VAS scores between the 2 groups (Table 2). At 1 week, 1 month, and 3 months after treatment, both groups showed significant reductions in VAS scores compared to baseline. Inter-group comparisons revealed no significant differences in VAS scores at 1 week and 1 month after treatment. However, at 3 months after treatment, the observation group had significantly lower VAS scores than the control group.

FOOT FUNCTION:

There was no significant difference in AOFAS ankle-hindfoot function scores between the 2 groups before treatment (P>0.05) (Table 3). At 1 week, 1 month, and 3 months after treatment, both groups had significant improvements in AOFAS scores compared to baseline (P<0.05). Inter-group comparisons revealed that there was no significant difference in the AOFAS ankle-hindfoot function scores between the 2 groups at 1 week and 1 month after treatment (P>0.05). However, at 3 months after treatment, the observation group had significantly higher AOFAS scores than the control group (P<0.05).

PLANTAR FASCIA THICKNESS:

Regarding plantar fascia thickness, there was no significant difference between the 2 groups before treatment (P>0.05) (Table 4). Intra-group comparisons showed that plantar fascia thickness did not change significantly at 1 week after treatment compared to baseline in both groups (P>0.05). However, at 1 month and 3 months after treatment, both groups had significant thinning of plantar fascia thickness compared to baseline (P<0.05). Inter-group comparisons revealed no significant difference in plantar fascia thickness at 1 week after treatment (P>0.05), but significant differences were observed at both 1 month and 3 months after treatment (P<0.05).

ADVERSE EVENTS:

All adverse events (AEs) in both groups were closely monitored and systematically recorded throughout the intervention period and the 3-month follow-up. In the observation group (Zhengqing Fengtongning injection, n=27), 1 patient (3.7%, 1/27) experienced a mild AE, which presented as slight pruritus at the injection site. This symptom resolved spontaneously without additional intervention after approximately 4 hours, and no moderate or severe AEs were reported in this group.

In the control group (corticosteroid injection, n=27), 1 patient (3.7%, 1/27) also developed a mild AE, manifested as pain at the injection site. The pain occurred within 4 hours after injection, with a VAS score of 2, and disappeared completely after 24 hours of cold compress application. Consistent with the observation group, no severe AEs were observed in the control group.

Statistical analysis confirmed that there was no significant difference in the overall incidence of AEs between the 2 groups (P>0.05). These results indicate that both ultrasound-guided injection regimens exhibit comparable short-term safety profiles, with only mild, self-limiting AEs reported, supporting their clinical applicability in patients with chronic plantar fasciitis.

Discussion

This study, through ultrasound-guided comparative injections, demonstrated that Zhengqing Fengtongning was comparable to corticosteroids in short-term analgesia and functional improvement for plantar fasciitis, but showed superior long-term efficacy at 3 months, accompanied by more pronounced thinning of the plantar fascia. These findings not only validate Zhengqing Fengtongning’s clinical potential but also offer a novel perspective for treating chronic fascial disorders.

Ultrasound guidance significantly enhanced target localization precision, with no between-group differences in VAS and AOFAS score improvements at 1 week and 1 month – indicating equivalent short-term anti-inflammatory and analgesic effects. This aligns with corticosteroids’ potent acute anti-inflammatory action via COX-2 and NF-κB pathway inhibition, while Zhengqing Fengtongning achieves rapid pain relief through histamine-mediated immediate analgesia [18,19] and μ-opioid receptor activation by sinomenine [13]. McMillan et al [20] previously confirmed ultrasound-guided precision delivery to the fascial surface; our study further shows that accurate targeting optimizes short-term efficacy for both biological agents (corticosteroids) and herbal extracts (Zhengqing Fengtongning).

At 3 months, the observation group’s advantages in VAS (1.96±0.33 vs 2.81±0.48) and AOFAS scores (87.81±1.88 vs 85.85±2.68) highlight Zhengqing Fengtongning’s unique value in long-term symptom control and functional recovery. This may be related to its multi-target mechanism: (1) Sustained anti-inflammation and immune regulation: Sinomenine inhibits the NF-κB pathway to reduce TNF-α, IL-6 and downregulates T-cell NF-AT signaling to suppress excessive immune responses [21–26], blocking chronic inflammatory cycles more effectively than acute-phase inflammatory inhibition. (2) Tissue repair promotion: The Zhengqing Fengtongning group exhibited significantly greater plantar fascia reduction in thickness at 1 month (4.49±0.16 mm vs 4.60±0.13 mm), suggesting it can accelerate fascial fiber repair and remodeling by improving local microcirculation (eg, enhancing capillary permeability) [27]. In contrast, long-term corticosteroid use can disrupt matrix metalloproteinases (MMPs), delaying tissue repair [28,29]. (3) Sustained local action: Ultrasound-guided focal injections create prolonged drug concentration at the lesion, combined with Zhengqing Fengtongning’s sustained-release profile (10 sessions vs 2 corticosteroid injections), enabling continuous treatment of diseased fascia. Corticosteroid efficacy decays rapidly with metabolism, making it insufficient for use in chronic inflammatory environments.

The lack of significant plantar fascia thickness change at 1 week aligns with the chronic nature of fascial degeneration – short-term inflammation control relieves pain, but structural repair requires time. Significant thinning in both groups at 1 month (more pronounced with Zhengqing Fengtongning) indicates Zhengqing Fengtongning’s potential superiority in promoting fascial structural repair.

While the control group showed notable short-term efficacy, corticosteroids’ long-term risks (eg, fascia tear, fat pad atrophy) limit their use [30–32]. The Zhengqing Fengtongning group reported only mild adverse events (rash, pruritus, flushing), consistent with its immunomodulatory rather than immunosuppressive mechanism [13,33]. This safety profile is particularly valuable for patients requiring repeated injections, offering a safer long-term management option.

This study has several limitations, including a small sample size (n=54) and a relatively short follow-up period (3 months). Future research should prioritize multi-center, long-term follow-up studies (eg, 1-year follow-up) to observe differences in recurrence rates. Additionally, incorporating MRI assessments of fascial fibrosis and serum inflammatory cytokine measurements (eg, IL-10, TGF-β) could further clarify the specific mechanisms by which Zhengqing Fengtongning promotes tissue repair. A further limitation is that the differing injection frequencies between the 2 groups were determined based on the inherent pharmacological properties of the respective agents. While we minimized potential confounding by strategically aligning outcome assessment time points, we cannot fully rule out the possibility of minor efficacy effects attributable to injection frequency itself. To resolve this ambiguity and optimize the therapeutic regimen, future randomized controlled trials specifically comparing different injection frequencies of Zhengqing Fengtongning are warranted.

Conclusions

Ultrasound-guided Zhengqing Fengtongning injections demonstrated superior long-term efficacy and safety compared to corticosteroids for plantar fasciitis. Notwithstanding these outcomes, caution is warranted – study constraints mean designating it as a novel standard of care remains premature, although it is a promising therapeutic option. This work provides clinicians with an evidence-based alternative for managing the condition, while further validation through future research is required to confirm its long-term utility.