The Effectiveness of Ultrasound-Guided Glucose Combined with Mecobalamin Neurolysis in Treating Patients with Refractory Painful Peripheral Neuropathy Using the DCEC Ultrasound Score: A Retrospective Study

Abstract

Objective

This study aimed to to evaluate the efficacy and safety of hydrodissection in refractory painful peripheral neuropathy over six months, and to explore whether the DCEC ultrasound scoring system predicts treatment response.

Methods

The study included 57 patients diagnosed with intractable painful peripheral neuropathy confirmed by neuroelectrophysiology who visited the outpatient or inpatient departments of the Affiliated Hospital of Guizhou Medical University from March 2023 to June 2024. All patients underwent nerve ultrasound examination and were scored using the DCEC ultrasound scoring system, as well as neurological function assessments (including the Michigan Neuropathy Screening Tool, Toronto Clinical Scoring Scale, and Short-Form McGill Pain Questionnaire). All patients were divided into two groups: the first group consisted of 18 patients with diabetic painful peripheral neuropathy, and the second group consisted of 39 patients with non-diabetic painful peripheral neuropathy. The adverse reactions and complications of both groups after nerve hydrodissection treatment were recorded. The correlation between nerve ultrasound DCEC scores, Michigan and Toronto scores, and visual analog scale (VAS) and Short-Form McGill scores before and after treatment was analyzed.

Results

The VAS scores and SF-MPQ scores of both patient groups showed significant improvement at 1, 2, 3, and 6 months after treatment compared to before treatment (P<0.001), but there was no significant difference between the two groups. At 3 and 6 months, the percentage of patients with ≥50% improvement both in VAS scores and SF-MPQ scores were higher in the DPPN group compared to the NDPPN group (P=0.004, P=0.021, P=0.001, P=0.016). The clarity score of nerve ultrasound in the affected limb is correlated with pain improvement after treatment (P=0.015).

Conclusion

Ultrasound-guided nerve hydrodissection may provide pain relief for patients with intractable painful peripheral neuropathy and has good safety. Further controlled studies are needed to confirm its efficacy.

Introduction

Painful peripheral neuropathy (PPN) is defined as neuropathic pain occurring in the acute or chronic phase of lesions or diseases affecting the peripheral nervous system.¹ Studies show the prevalence of neuropathic pain is 7–10%.²

The tibial nerve arises from the sciatic nerve and descends into the posterior compartment of the lower leg deep to the soleus, plantaris, and gastrocnemius muscles. It then enters the tarsal tunnel, which is formed by the calcaneus, talus, medial malleolus and flexor retinaculum—entrapment is common at this site and is termed “tarsal tunnel syndrome”.

Current clinical treatments for neuropathic pain primarily include pharmacological therapy and minimally invasive interventions.^3,4 In the pharmacological management of neuropathic pain, anticonvulsants (such as gabapentin, pregabalin), antidepressants (such as amitriptyline), and serotonin-norepinephrine reuptake inhibitors (such as duloxetine and venlafaxine) are first-line treatments.^5,6 However, the success rate for treating neuropathic pain with non-steroidal anti-inflammatory drugs (NSAIDs), opioids, antidepressants, or anticonvulsants is estimated to be between 30% and 50%,⁷ and these medications may also have significant adverse effects. The latest guidelines suggest that patients intolerant to pregabalin adverse effects can switch to Crisugabalin,⁸ which still has minor adverse effects such as dizziness, drowsiness, peripheral edema, weight gain, nausea, vomiting, and malaise.⁹ Topical medications (such as lidocaine patches, high-concentration capsaicin cream, or patches) are second-line treatments,^1,10 and third-line treatments include strong opioids and Botulinum Toxin-A (BTX-A). Minimally invasive interventions include nerve blocks, nerve electrical stimulation, pulsed radiofrequency, etc.

Hydrodissection was first proposed in 1997 and was later used to treat nerve entrapment diseases,¹¹ such as carpal tunnel syndrome, termed nerve hydrodissection. Nerve hydrodissection (HD) is a technique for treating nerve entrapment, involving the injection of anesthetics, normal saline, or dextrose solution, etc, to separate the nerve from surrounding tissues, fascia, or adjacent structures.¹² The injected liquid physically separates the nerve from the surrounding contracting tissue, dissolves adhesions, and effectively enlarges the space around the nerve. This immediately reduces mechanical compression and restores normal nerve sliding; The neuromodulatory effect of glucose: As a mild stimulant, glucose can stimulate healing and possesses neuromodulatory properties. It is speculated that it can stabilize neuronal membranes, reduce ectopic discharges, and modulate pain receptors such as TRPV1, thereby reducing neurogenic inflammation and pain signal transmission.^13,14 Mecobalamin is the active neurotrophic component, a coenzyme for methionine synthase critical for myelin phospholipid synthesis.

The advantages of ultrasound-guided hydrodissection include scarless operation, greater safety, the ability to perform the procedure in an outpatient setting, and rapid return to daily activities. Secondly, it can provide alternative treatment for patients with PPN who have poor response to medications or experience significant side effects.¹⁵ Ultrasound allows direct visualization of key anatomical structures such as nerves, blood vessels, and tendons, providing accuracy and safety for the procedure and minimizing the risk of complications. Ultrasound-guided hydrodissection can significantly improve neuropathic pain caused by carpal tunnel syndrome.^16,17

In addition, previous case reports from our research group have also confirmed that ultrasound-guided neurolysis therapy can improve muscle weakness and sensory symptoms in patients with refractory diabetic peripheral neuropathy after 1–2 courses of treatment, with few adverse reactions and good patient tolerance. However, its long-term effectiveness and safety still need further verification.¹⁸ To this end, our research group has designed the following approach: patients with refractory diabetic and non-diabetic painful peripheral neuropathy who have undergone full courses of standard treatment (oral mecobalamin + vitamin B1 for at least one month) but have shown poor efficacy will undergo 5% or 10% glucose combined with mecobalamin neurolysis therapy around the diseased nerve. Regular follow-ups will be conducted to assess the improvement of pain after treatment, as well as to evaluate safety. Furthermore, we will explore the relationship between the DCEC ultrasound scoring system and the prognosis of patients with refractory painful peripheral neuropathy who undergo neurolysis therapy.

Materials and Methods

Patients

This was a retrospective study approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University (Approval No. 2025 Ethical Review 277). The research conforms to the Declaration of Helsinki.

Between March 2023 and June 2024, fifty-seven patients ultimately met the criteria and completed the 6-month follow-up (Figure 1). All patients were diagnosed with refractory painful peripheral neuropathy and received ultrasound-guided hydrodissection treatment. Baseline symptom duration, number of hydrodissection sessions, neuromuscular ultrasound data, and follow-up telephone visit times were retrieved. All patients underwent neurological function tests. A research assistant conducted telephone interviews. Patients were assessed at 1, 2, 3, and 6 months after the intervention.

Figure 1.

Flowchart of Patient Enrollment.

Inclusion and Exclusion Criteria

Inclusion criteria were as follows: (1) Age 18–80 years, diagnosed with refractory painful peripheral neuropathy: Patients should have tried at least four known effective drugs, each for at least 3 months (or at the maximum tolerated dose), or despite treatment, pain intensity reduction was less than 30%, or it remained at least 5 on a 0–10 VAS scale and/or continued to significantly cause low quality of life;¹⁹ (2) Disease course ≥ 3 months; (3) Neuropathy manifested as decreased sensation and numbness in the affected area, or tingling, burning, and/or pain; (4) Able to read and understand questionnaires and clinical assessments; able to read, understand, and sign written informed consent; (5) Ultrasound were conducted to confirm nerve compression.

Exclusion criteria were as follows: Exclusion of peripheral neuropathies predominantly with motor symptoms, neuromuscular diseases, hereditary neuropathies, patients with lower limb surgery, lower limb vascular occlusion, hypokalemic periodic paralysis, hyperthyroid myopathy, individuals engaged in specific sports, malignant tumors, alcohol dependence, peripheral neuropathy caused by neurotoxic drugs (such as anticholinergics, local anesthetics, etc), and those with limb movement disorders due to other causes such as stroke or trauma; exclusion of severe cardiopulmonary insufficiency, obvious muscle weakness, allergy to coupling gel, inability to cooperate with high-frequency ultrasound examination.

Ultrasound Examination

Ultrasound examination included measuring nerve cross-sectional area (CSA), Clarity, echogenicity, and compression. Neuroultrasound scoring - DCEC uses clarity (definition, D), cross-sectional area (C), echogenicity (E), and compression (C) as observation indicators. The definitions of each observation indicator are as follows: ① Clarity of nerve visualization: a. Clear, scored 0, indicating that the nerve epineurium presents as a high-echo ring, with an internal “sieve-like” structure of alternating high and low echoes, and the boundary between the nerve and surrounding tissues is clear; b. Slightly blurry, scored 1, indicating that the nerve visualization presents as a “frosted glass” appearance, with the internal “sieve-like” structure visible, and the boundary between the nerve and surrounding tissues is acceptable; c. Blurry, scored 2, indicating that the nerve epineurium presents as a “residual shadow” under ultrasound, the internal “sieve-like” structure disappears, and the boundary between the nerve and surrounding tissues is poor; d. Unclear, scored 3, indicating that both the high-echo ring structure of the nerve epineurium and the internal “sieve-like” structure disappear, making it impossible to distinguish between the nerve and surrounding tissues. The higher the score, the worse the clarity. ② Cross-sectional area of the nerve: a. Within the normal range, scored 0; b. ≥ normal value and ≤ 150% of normal value, scored 1; c. > 150% of normal value, scored 2. The normal value of cross-sectional area refers to our previous research. ③ A normal echo of the nerve is scored as 1 point, and any reduction in echo, where low echo replaces the normal sieve-like structure within the nerve or increases, is scored as 1 point. ④ If there is no compression of the nerve during its course, scored 0; if there is compression, where the nerve becomes thinner at the compressed site and both ends of the nerve are slightly thicker but the continuity remains intact, scored 1. The ultrasound scoring system (DCEC) equals the total score (score of each nerve = clarity score + cross-sectional area score + echogenicity score + compression score of each nerve), including the total scores of the upper and lower limbs; the above scores are calculated by one researcher. Details are in the scoring system (Supplementary Table 1).

Procedure

Before the procedure, ultrasound examination was performed by ultrasound researchers experienced in musculoskeletal ultrasonography, using an ultrasound system equipped with a 5 to 12 MHz linear array transducer (Philips Ultrasound iU22, Netherlands).

Each patient was in a sitting or prone position. Based on our experience, after ensuring no wounds at the local skin site, the target nerve (defined as the nerve responsible for the patient’s symptoms, the one actually causing or indirectly leading to these symptoms) was approached. The injection site was disinfected with povidone-iodine (Guizhou Xinyuan). After disinfection, the ultrasound probe was covered with a sterile glove. The needle was inserted at a 90-degree angle. Fluid delivery was monitored by visual observation of the injection or the ultrasound screen. Under sterile conditions, using an out-of-plane approach, HD was performed under US guidance using a 27 G needle. During injection, patients were asked about shooting pain or severe burning sensation to avoid direct injection into the nerve. Patients were observed for 30 minutes post-injection for allergic reactions. Ultrasound images before and after nerve hydrodissection were shown (Figure 2).

Figure 2.

Ultrasound of a patient before and after Hydrodissection. The transverse ultrasound image of the tibial nerve before hydrodissection (A); The transverse ultrasound image of the tibial nerve after hydrodissection (B). The tibial nerve in longitudinal view, the nerve is indicated by a*, and the hydrodissection plane is indicated by a triangle Δ.

Neurological Function Assessment and Follow-Up

All neurological function assessments were recorded on unified forms, completed by dedicated researchers questioning the patients. Pre-treatment assessments were completed upon patient admission. Follow-up assessments were completed via patient hospital visits or telephone follow-up. Pain was assessed using VAS and the Short-Form McGill Pain Questionnaire (SF-MPQ) at five time points: before injection, and at 1, 2, 3, and 6 months after injection. The VAS pain assessment were explained to patients (by selecting a number representing their pain, 0 = no pain, 10 = worst pain imaginable).

Statistical Methods

First, the independent samples t-test was used to compare normally distributed continuous data between the two groups, with data expressed as mean ± standard deviation; the Mann–Whitney U-test was used to compare non-normally distributed continuous data between the two groups, with data expressed as median [interquartile range]; and the chi-square test was used for categorical variables, with data expressed as frequency (percentage). All data analyses were performed using SPSS software (version 26.0, SPSS Inc., Chicago, IL). A P-value < 0.05 was considered to be significant.

Second, repeated-measure analysis of variance (ANOVA) was used to compare whether VAS scores and SF-MPQ scores changed over treatment time in the diabetic group, non-diabetic group, and the total population. Corrected the spherical hypothesis using the Greenhouse-Geisser correction or the Huynh-Feldt correction.

Finally, multiple linear regression analysis was used to analyze the correlation between the affected limb nerve ultrasound Clarity DCEC score and the SF-MPQ score at 1 month post-treatment. Model II was established on the basis of model I, corrected for possible confounding factors such as age, gender, course of disease, hypertension, diabetes, dyslipidemia, and the ultrasound cross-sectional area score of the affected limb nerves (Based on domain knowledge, covariates (such as age, gender, past medical history, etc) are included).

Results

All patients participating in the study received hydrodissection treatment once a week for at least one consecutive month. A total of 86 patients with refractory painful peripheral neuropathy who received treatment were initially enrolled in Affiliated Hospital of Guizhou Medical University from March 1, 2023 to June 13, 2024, and 57 patients were finally eligible, having had complete follow-up (Figure 1).

Among the 57 patients, 34 (59.6%) were female, with a mean age of 58.77 ± 11.57 years. The median (interquartile range) disease duration was 2 [5.00] years in the DPPN group, and 1 [1.50] years in the NDPPN group (Table 1). The scores of the Michigan Questionnaire, Michigan Physical Examination, and Toronto Clinical Scoring System in the DPPN group were all higher than those in the NDPPN group, and the differences were statistically significant (P <0.001, P =0.001, P =0.046) (Table 2).

Table 1.

Demographic Information and Clinical Data Characteristics in the Diabetic Painful Peripheral Neuropathy (DPPN) and Non-Diabetic Painful Peripheral Neuropathy (NDPPN) Groups (n=57)

Characteristics	DPPN Group (n=18)	NDPPN Group (n=39)	Overall (n=57)	t/z/χ2	P
Age (mean ± SD, y)	66.72±9.61	55.10±10.60	58.77±11.57	3.958	<0.001*
Females, no.(%)	10.00 (66.70)	24.00 (53.30)	34.00 (54.00)	0.026	0.764†
Height, mean (SD), cm	161.11±7.67	161.79±8.09	161.58±7.89	−0.301	0.714*
Weight, mean (SD), kg	64.56±15.56	61.79±8.60	62.67±11.20	0.863	0.392*
BMI, mean (SD), kg/m2	25.01±6.57	23.58±2.56	24.03±4.24	1.186	0.241*
Duration, M[Q], y	2.00 [5.00]	1.00 [1.50]	1.00 [2.50]	−1.347	0.178‡
Dyslipidemia, no.(%)	12.00 (66.70)	23.00 (59.00)	35.00 (61.40)	0.307	0.579†
Hypertension, no.(%)	10.00 (55.60)	10.00 (25.60)	20.00 (35.10)	4.839	0.028†
Arrhythmia, no.(%)	2.00 (11.10)	0.00 (0.00)	2.00 (3.50)	4.491	0.034†
Smoking history, no.(%)	3.00 (16.70)	7.00 (15.60)	10.00 (15.9)	0.031	0.859†
Drinking history, no.(%)	2.00 (11.10)	4.00 (8.90)	6.00 (9.50)	0.105	0.746†

Notes: *Independent t-test is used to compare two groups of measurement data that follow a normal distribution, with data expressed as mean ± standard deviation; † Chi-square test is used for comparing two groups of count data, with data expressed as frequency (ratio). ^‡ Mann–Whitney U-test is used to compare two groups of measurement data that follow a skewed distribution, with data expressed as median [interquartile range].

Abbreviations: DPPN group, Diabetic painful peripheral neuropathy group; NDPPN group, Non-diabetic painful peripheral neuropathy group; BMI, body mass index; SD, standard deviation; M, median; Q, interquartile range; y, year.

Table 2.

Pre Treatment DCEC and Scale Scores of the Research Sample (n=57)

Characteristics	DPPN Group (n=18)	NDPPN Group (n=39)	Overall (n=57)	z/t	P
Neuroultrasound of the affected limb DCEC Score, M[Q]
DCEC Score	6.50 [5.90]	7.00 [4.00]	7.00 [4.25]	−0.207	0.836‡
Clarity Score	6.00 [7.30]	6.00 [5.00]	6.00 [5.00]	−0.225	0.822‡
Cross sectional area rating Score	1.00 [2.10]	2.00 [2.50]	1.50 [2.50]	−0.614	0.539
Echo Score	0 [0]	0 [0]	0 [0]	−0.271	0.786‡
Card pressure Score	0 [0]	0 [0]	0 [0]	−0.897	0.370‡
MNSI, M[Q]
Questionnaire Score	2.50 [3.00]	1.00 [2.00]	1.00 [2.00]	−3.507	<0.001‡
Physical Examination Score	2.00 [0.90]	0.00 [2.00]	1.00 [2.00]	−3.385	0.001‡
TCNS Score, M[Q]	6.50 [7.00]	5.00 [5.00]	6.00 [7.50]	−1.905	0.046‡
VAS Score, mean ± SD	6.11±2.32	5.59±2.33	5.75±2.32	0.787	0.435*
SF-MPQ Score, mean ± SD	14.11±6.39	11.18±5.03	12.11±5.61	1.876	0.066*

Notes: *Independent t-test is used to compare two groups of measurement data that follow a normal distribution, with data expressed as mean ± standard deviation; ^‡Mann–Whitney U-test is used to compare two groups of measurement data that follow a skewed distribution, with data expressed as median [interquartile range].

Abbreviationssectional area, echo, and compression.

The VAS scores and SF-MPQ scores of both patient groups showed significant improvement at 1, 2, 3, and 6 months after treatment compared to before treatment, but there was no significant difference between the two groups. Table 3 and Figure 3 summarize the details of the comparison between groups.

Table 3.

Changes in VAS and SF-MPQ Scores with Treatment Time (n=57)

Scale Scoring	DPPN Group (n=18)	NDPPN Group (n=39)	Overall (n=57)	P1
VAS Score,
Before treatment	6.11±2.32a	5.59±2.32a	5.75±2.31	0.435
One month after treatment	3.66±1.79b	3.71±2.36b	3.70±2.18	0.938
Two months after treatment	3.16±1.59c	3.31±2.24c	3.27±2.04	0.798
Three months after treatment	2.98±1.94bc	2.94±2.36c	2.97±1.92	0.975
Six months after treatment	2.94±2.36bc	2.88±2.16c	2.90±2.21	0.929
P2	<0.001	<0.001
P3	0.921	0.921
SF-MPQ Score,
Before treatment	14.11±6.38a	11.18±5.03a	12.11±5.60	0.066
One month after treatment	9.25±6.57b	7.33±3.89b	7.93±4.92	0.173
Two months after treatment	8.16±6.15bc	6.15±3.68b	6.69±4.57	0.153
Three months after treatment	6.82±5.03c	5.88±3.66b	6.17±4.12	0.428
Six months after treatment	6.80±5.51bc	5.73±4.18b	6.07±4.62	0.420
P2	<0.001	<0.001
P3	0.498	0.498

Notes: P¹ indicates intergroup comparison, P² indicates time comparison, P³ indicates time*group comparison. a, b, c, d e represent the results of intragroup post-hoc tests, with identical letters indicating no statistically significant differences within the group and different letters indicating statistically significant differences within the group.

Abbreviations: , mean; s, standard deviation.

Figure 3.

Changes in VAS and SF-MPQ Scores Over Treatment Time in the DPPN Group, and NDPPN Group, Overall. (A) shows the changes of VAS scores in DPPN group, NDPPN group and treatment time; (B) shows the changes of SF-MPQ scores in DPPN group, NDPPN group and treatment time. There was no significant difference between DPPN group and NDPPN group before treatment and at any follow-up time point. Error bars indicate 95% CIs. (GraphPad Prism, 9, GraphPad Corporation).

At 3 and 6 months, the percentage of patients with ≥50% improvement both in VAS scores and SF-MPQ scores were higher in the DPPN group compared to the NDPPN group (P=0.004, P=0.021, P=0.001, PTable 4).

Table 4.

Number of Individuals Whose VAS Scores and SF-MPQ Scores Decreased By≥ 50% Compared to Baseline Between the Two Groups

	DPPN Group (n=18)	NDPPN Group (n=39)	χ2	P
Number of patients whose VAS score decreased by ≥ 50% compared to before treatment, n (%)
One month after treatment	8 (44.4)	18 (46.2)	0.015	0.904†
Two months after treatment	11 (61.1)	20 (51.3)	0.480	0.489†
Three months after treatment	16 (88.9)	19 (48.7)	8.386	0.004†
Six months after treatment	15 (83.3)	20 (51.3)	5.338	0.021†
SF-MPQ score decreased by ≥ 50% compared to before treatment, n (%)
One month after treatment	6 (33.3)	11 (28.2)	0.155	0.694†
Two months after treatment	11 (61.1)	14 (35.9)	3.180	0.075†
Three months after treatment	15 (83.3)	14 (35.9)	11.088	0.001†
Six months after treatment	14 (77.8)	17 (43.6)	5.803	0.016†

Note: ^†The chi square test is used for two sets of counting data, and the data is expressed in frequency (ratio).

Multiple linear regression revealed an association between the affected limb nerve ultrasound Clarity score and the SF-MPQ score at 1 month post-treatment in patients with painful peripheral neuropathy (Table 5 and Supplementary Table 2). Among them, the echogenicity and compression scores were very low and were not included in the statistics. Worse nerve Clarity was associated with a higher SF-MPQ score at 1 month post-treatment. The VAS scores showed no correlation with the ultrasonographic Clarity, cross-sectional area scores, or total scores of the affected limb nerves at any follow-up time point (Supplementary Table 3).

Table 5.

The Impact of Ultrasound Clarity Score of Affected Limb Nerves on SF-MPQ Score One month After Treatment (n=57)

Model	Independent Variable	SF-MPQ (Dependent Variable)
		β	[95% CI]	P
I	Ultrasound Clarity score of affected limb nerves	0.527	[0.038; 0.349]	0.015
II†	Ultrasound Clarity score of affected limb nerves	0.358	[−0.106; 0.822]	0.127

Notes: β is the regression coefficient reflecting the increase or decrease of SF-MPQ. Model I analyzed the relationship between the ultrasound clarity score of the affected limb nerves and SF-MPQ. † Model II was established on the basis of model I, corrected for possible confounding factors such as age, gender, course of disease, hypertension, diabetes, dyslipidemia, and the ultrasound cross-sectional area score of the affected limb nerves.(Based on domain knowledge, covariates (such as age, gender, past medical history, etc) are included).

Abbreviation: CI, Confidence interval.

Higher Michigan Questionnaire and Toronto scores were associated with higher pre-treatment SF-MPQ scores (P =0.002, P =0.024). The Michigan Questionnaire scores and Toronto scores in patients with painful peripheral neuropathy were also associated with SF-MPQ scores at 1 and 2 months after treatment (P =0.005, P =0.030; P =0.005, P =0.008). Patients with higher Michigan Questionnaire and Toronto scores had higher SF-MPQ scores at 1 and 2 months after hydrodissection treatment, indicating slower recovery (Supplementary Table 4). However, no association was found between the Michigan Questionnaire scores, Michigan Physical Examination scores, or Toronto scores and post-treatment VAS scores in patients with painful peripheral neuropathy (Supplementary Table 5).

Adverse Events

No serious adverse events were observed during the trial. However, five minor adverse events occurred. These adverse events included: 2 cases of distending pain at the injection site, 2 cases of subcutaneous ecchymosis at the injection site, and 1 case of worsened pain after injection.

Discussion

Traditional treatments for painful peripheral neuropathy typically involve two main approaches, including pharmacological and non-pharmacological management, such as anticonvulsants, tricyclic antidepressants, opioids, topical medications, repetitive transcranial magnetic stimulation, or pulsed radiofrequency. However, the above management methods are ineffective for some painful peripheral neuropathies, and pharmacological management has significant side effects, while non-pharmacological management like spinal cord stimulation is relatively expensive. Therefore, it is necessary to explore new treatment methods to provide alternative options after the failure of the above treatments. Ultrasound-guided hydrodissection introduces high-frequency ultrasound based on nerve hydrodissection. Under high-frequency ultrasound guidance, the anatomical structure of the nerve is clear, and damage to blood vessels and nerves is minimal. Another advantage is that it allows for targeted injection, precisely releasing the entrapped nerve from surrounding tissues to improve the effectiveness of hydrodissection. Due to the higher baseline VAS scores in patients with diabetic painful peripheral neuropathy, patients with DPPN may experience greater improvement compared to those with NDPPN. Therefore, it is emphasized that clinical decision-making should rely more on absolute pain relief values (the proportion of VAS ≤ 3) rather than solely on percentage improvement.

Efficacy of Hydrodissection

Solutions used for hydrodissection often include 5% or 10% dextrose or 0.9% normal saline, combined with hormones, lidocaine, mecobalamin, etc. Dextrose injection is used as a solution for perineural injection because it is similar to normal saline. Although 5% dextrose (equal to 5000 mg/dL) is about 50 times higher than the physiological concentration in plasma and tissue fluid, the osmolarity of 5% dextrose (277 mmol/L) is similar to normal saline (308 mmol/L) and has no harmful effects on nerve tissue.²⁰ Studies have also proven that perineural injection of 5% dextrose is more effective than perineural injection of normal saline,^15,21 with good safety.^22–24 10% dextrose usually triggers an inflammatory cascade and is used to treat musculoskeletal pain.²⁵ It induces an inflammatory reaction at the injection site, inducing fibroblast proliferation and subsequent collagen formation. This strengthens tendons and ligaments at the injection site. In this study, 5% or 10% dextrose injection plus 0.5mg mecobalamin injection was selected as the formula for treatment. Diabetic patients received 5% dextrose injection, while non-diabetic patients received 10% dextrose injection, to better achieve pain relief.

Mechanism of Hydrodissection

The mechanism of hydrodissection for peripheral neuropathy can be divided into mechanical and pharmacological effects.¹⁹ The non-specific effect of fluid under external force separates the nerve, which can gradually reduce adhesions, increase blood flow, and restore nerve blood supply. A cadaver study demonstrated that ultrasound-guided hydrodissection can reduce the sliding resistance of the median nerve in the carpal tunnel, indicating that ultrasound-guided hydrodissection can mechanically move the median nerve relative to the surrounding carpal tunnel structures.²⁶

Local dextrose injection can alleviate pain,²⁷ but its pharmacological mechanism is unclear. One hypothesis is that dextrose may reduce neurogenic inflammation by inhibiting Transient Receptor Potential Vanilloid-1 (TRPV1). Inhibiting TRPV1 can limit neurogenic inflammation by blocking neurotransmitters such as Calcitonin Gene-Related Peptide and Substance P.²⁰ Additionally, previous studies found that after perineural dextrose injection, nerve electrophysiology also improved, suggesting that dextrose might promote nerve regeneration.²³ Therefore, further basic research is needed to explore the exact mechanism of dextrose.

Mecobalamin is an active form of Vitamin B12, widely used in Asia, which can promote the synthesis of nucleic acids and proteins in neurons. It also promotes axonal regeneration and myelin formation, improving nerve function; therefore, mecobalamin can help repair damaged nerve cells and improve nerve conduction.²⁸ Injection around the affected nerve may facilitate the absorption and utilization of mecobalamin by peripheral nerve tissues.

Relationship Between DCEC Score and SF-MPQ Score One Month After Hydrodissection

Recently, ultrasonography has been increasingly used as a method alongside electrophysiology in the diagnosis of painful peripheral neuropathy, especially in diabetic peripheral neuropathy. It is relatively convenient, low-cost, free of radiation exposure, and provides dynamic assessment relatively easily. In previous studies, the use of ultrasonography for diagnosing peripheral neuropathy and predicting treatment efficacy was mainly based on the measurement of the cross-sectional area (CSA). However, the ultrasound scoring system used for such prediction—the UPSS score—only incorporated the nerve’s cross-sectional area, lacking description of nerve Clarity, echogenicity, etc. Based on preliminary research and experience, this study summarized the DCEC ultrasound scoring system, evaluating four aspects: nerve Clarity, cross-sectional area, echogenicity, and compression, yielding scores for each item and a total score. It indicated a correlation between the Clarity score item in the affected limb nerve ultrasound DCEC assessment and the SF-MPQ score at 1 month post-treatment. Worse nerve Clarity was associated with a higher SF-MPQ score at 1 month post-treatment. Furthermore, an association was found between the affected limb nerve ultrasound DCEC score and the SF-MPQ score at 1 month post-treatment. A higher affected limb nerve ultrasound score was associated with a higher SF-MPQ score at 1 month post-treatment. Simultaneously, in this study, after hydrodissection treatment, we observed immediate improvement in nerve Clarity. Unfortunately, this study did not design post-treatment nerve ultrasound DCEC score observation. Future research could focus on this direction.

Limitations

Firstly, two patients were diagnosed with anxiety and depression and were treated with oral antidepressants, which may affect the VAS and SF-MPQ scores. Secondly, 5% glucose/mecobalamin was used for DPN and 10% glucose for NDPN, and the difference in concentration between the two injections may affect the follow-up results. Thirdly, no sample size calculation was conducted, and the high attrition rate may introduce selection bias. Fourthly, telephone follow-up, recall bias, and lack of blinding; the lack of blinding may lead to placebo response. Fifthly, the number of treatment sessions varied, with at least 4 sessions and up to 23 sessions, which may affect the results; lastly, there may be a placebo effect due to the lack of blinding.

A multi-center, prospective randomized controlled trial was employed to minimize bias; follow-up should incorporate objective assessments of nerve function and mobility using electromyography and dynamic ultrasound; blinded outcome assessors or placebo-controlled designs were used to minimize subjectivity in outcome reporting; these investigations should include careful assessment of baseline metabolic status and related psychological comorbidities. In summary, although this report highlights a potential new hypothesis for the effectiveness of ultrasound-guided glucose combined with mecobalamin neurolysis in patients with refractory painful peripheral neuropathy, the study results should be interpreted with caution. Future prospective, multi-center studies are necessary to elucidate the therapeutic effect.

Conclusion

Ultrasound-guided nerve hydrodissection may provide pain relief for patients with intractable painful peripheral neuropathy and has good safety. Further controlled studies are needed to confirm its efficacy.

Funding Statement

This work was supported by Natural Science Foundation of Guizhou Province, China (Grant Qian Ke He Foundation (2022) No.417), The Guizhou Provincial Clinical Medical Research Center Construction Project - Neurological Disease Research (No: LCZX[2025]003),The “Summit Plan” Project for the Construction of Clinical Key Specialties by Guizhou Provincial Health Commission (GZWJWDF2025003),The Key Advantageous Discipline Construction Project of Guizhou Provincial Health Commission in 2023, China, 2024 Basic Research Program (Natural Sciences) Youth Guidance Project, Qiankehe Foundation - [2024] Youth 267 and A Study on the Efficacy and Mechanism of Ultrasound-Guided Perineural Hydrodissection in the Treatment of Peripheral Nerve Injury(2025GZYXKYJJXM0049).

Abbreviations

BTX-A, Botulinum toxin-A; CSA, Cross-sectional area; DCEC, Clarity, cross, Sectional area, echogenicity and compression; DPN, Diabetic Peripheral Neuropathy; DPPN, Diabetic Painful Peripheral Neuropathy; MNSI, Michigan Neuropathy Screening Instrument; NDPPN, Non-Diabetic Painful Peripheral Neuropathy; PDN, painful diabetic neuropathy; PHN, Postherpetic neuralgia; PPN, Painful peripheral neuropathy; SF-MPQ, Short-form McGill Pain Questionnaire; TCSS, Toronto clinical scoring system; TRPV1, Transient Receptor Potential Vanilloid 1; VAS, Visual analogue scales.

Data Sharing Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics Statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of the Affiliated Hospital of Guizhou Medical University (Approval No. 2025 Ethical Review 277) and with the 1964 Helsinki Declaration and its later amendments.

Author Contributions

Yining Qiu, Shan Wu: Conceptualization, Methodology, Writing – Original Draft. Yining Qiu, Chao Tang, Mi Li, Yuchan Lin, Shan He, Yan Li, Hong Deng, Yue Huang, Yinhe Long: Data Curation, Formal Analysis, Visualization.Yining Qiu, Shan Wu: Supervision, Funding Acquisition, Writing – Review & Editing.

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.