The Benefit of Perineural Injection Treatment with Dextrose for Treatment of Chondromalacia Patella in Participants Receiving Home Physical Therapy: A Pilot Randomized Clinical Trial

Abstract

Introduction:

Chondromalacia patella is the degeneration of articular cartilage on the posterior facet of the patella and may indicate the onset of osteoarthritis. Conservative management is the main treatment option, and surgical intervention is considered the last option in a small percentage of patients. Perineural Injection Treatment (PIT) is a recently developed treatment option that is directed adjacent to the peripheral nerves that are the source of pathology causing neurogenic inflammation and pain.

Objective:

The objective of this study was to evaluate the efficacy of PIT combined with a home physical therapy program in patients with a diagnosis of chondromalacia patella compared with a control group receiving physical therapy only.

Methods:

Two patient groups were involved in this randomized clinical trial. The first received PIT combined with physical therapy (PIT + PT group) and the second was managed with physical therapy alone (PT group). Both groups were indicated to follow a 6-week home therapy plan afterward. The Western Ontario and McMaster Osteoarthritis Index was used to assess the patients at baseline and 6 months after therapy interventions.

Results:

Fifty patients (38 women and 12 men, median age 54.7 ± 14.8 years) were included; sex distribution and age did not differ between groups. Both groups had chondromalacia grade II or III, but the degree of gonarthrosis did not differ significantly between groups. The PIT + PT group outperformed PT group for pain (7.3 ± 3.5 vs. 3.2 ± 2.9 points; p < 0.010), stiffness (3 ± 1.69 vs. 1.6 ± 1.5 points; p < 0.010), and functional capacity (23.2 ± 10.7 vs. 11.1 ± 8.9 points; p < 0.010).

Conclusions:

Compared with physical therapy alone, PIT plus physical therapy reduced pain and stiffness and restored functional capacity.

ClinicalTrials.gov Register Number #NCT03515720.

Introduction

Chondromalacia patella, also known as patellofemoral pain syndrome, is defined as the softening, thinning, and degradation of the cartilage on the posterior facet of the kneecap and can affect people at any age.¹ In adolescents and young adults, the condition is caused primarily by injury resulting from rupture of the intra-articular cartilage and can lead to the development of osteoarthritis.² In older adults, chondromalacia patella is primarily the result of age-related knee osteoarthritis.³ Conservative first-line therapy for chondromalacia patella includes exercise, physical therapy, nonsteroidal anti-inflammatory drugs, and corticosteroid and hyaluronic acid injections.⁴ Although temporary pain relief can be achieved with these treatments, they can eventually lead to cartilage degeneration with greater pain and functional disability, and eventually, a total knee replacement may be required.^5
–7 The number of knee replacements has increased dramatically. In 2005, almost 500,000 total knee replacements were performed at a cost exceeding 11 billion U.S. dollars. It is estimated that more than 1.5 million knee replacements will be needed in the future in the United States.⁸

Knee pain is one of the main reasons for consulting a rehabilitation service, and patellofemoral chondromalacia associated with gonarthrosis is the principal cause. A general prevalence of 15% for patellofemoral chondromalacia associated with gonarthrosis has been estimated in Mexico, and women are most frequently affected.⁹ Because of this high prevalence, the authors decided to explore perineural injection treatment (PIT) as a form of treatment to help reduce pain and functional limitations associated with participants with patellofemoral chondromalacia. PIT involves injecting 5% dextrose in a sterile aqueous solution, without the use of lidocaine, adjacent to a subcutaneous nerve. The clinical result of PIT is the reduction of signs and symptoms of neurogenic inflammation, and neurogenic inflammation is associated with release of substance P and calcitonin gene-related peptide. For that reason, it is proposed that PIT acts by altering the function of transmembrane cation channels on C fibers in such a way that the release of substance P and calcitonin gene-related peptide is inhibited.¹⁰ This decrease in neurogenic inflammation should allow the normal flow of nerve growth factors and nerve repair, and decrease pain.^11,12

This therapy has been used in multiple articular affections such as carpal tunnel syndrome,^13
–15 radial nerve palsy,¹⁶ ulnar neuropathy at the elbow,¹⁷ and complex regional pain syndrome.¹⁸ These studies reported that 5% dextrose PIT treatment had good and long-lasting effects on patients with pain when compared with saline solution injection or perineural corticosteroid treatment. Some reports have compared the application of dextrose and other types of therapies, such as saline solution, hyaluronic acid, or platelet-rich plasma, and have demonstrated that the use of dextrose injections is more effective than these alternatives.¹⁹

Given this background, the objectives of this study were to evaluate the effects of PIT combined with a home physical therapy program on pain, stiffness, and functional capacity in patients with chondromalacia patella, and to compare these with those induced by physical therapy alone.

Materials and Methods

Methods

This was a pilot randomized clinical trial. The statistical analyst was blinded to the results of the control and study groups. The participants were men and women with a clinical and radiographic diagnosis of chondromalacia patella referred to the Rehabilitation Unit of the Specialties Hospital of the Western Medical Center of the Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico, from January to October 2017. After the treatment intervention, all patients were followed for 6 months and then returned to the first-contact medical service of the institute for surveillance. The follow-up period ended in May 2018.

Patients

The inclusion criteria were men or women (>25 to <70 years of age) with a clinical and radiographic diagnosis of chondromalacia patella (grade II or III) with or without gonarthrosis. Patients were treated in the rehabilitation medicine service of the Specialties Hospital National Medical Center of the West. Patients were excluded if they had any of the following: corticosteroid injection into the knee within the past 12 months, septic arthritis, systemic infection, skin infection at the knee, systemic inflammatory disease, joint instability (ligament injury), meniscopathy, intra-articular fracture, coagulation disorder or treatment with anticoagulants, poorly controlled diabetes mellitus (blood glucose level >130 mg/dL), systemic arterial hypertension (>140/90 mmHg), hemarthrosis, pregnancy, or a cognitive disorder that prevented follow-up or completing the program.

Procedures

Using sealed-envelope assignment, patients were randomly allocated to receive PIT with physical therapy (PIT + PT group) or physical therapy alone (PT group). Allocation took place in a center located outside the rehabilitation unit by an external researcher not affiliated with the protocol. The allocation process is outlined in Figure 1. The PT group received physical therapy consisting of 10 sessions based on thermotherapy, kinesiotherapy, and muscle strengthening exercises for the knee. Each 1-hour session was held at the Physical Therapy and Rehabilitation Unit. After the initial program, the patients were instructed to perform this therapy daily at home for 6 weeks, after which time, the same measurements (knee movement angles, Western Ontario and McMaster Osteoarthritis Index [WOMAC], and pain visual analog scale [VAS] score) were obtained to identify any changes 6 months after the end of the treatment.

FIG. 1.

Patient enrollment flowchart. PIT, perineural injection treatment; PT, physical therapy.

In the PIT + PT group, pain areas were located along the course of the sensory nerves to the knee to identify points of chronic constriction (where the cutaneous nerve passes through the fascia). Once the painful points were identified and marked, the knee was prepared using aseptic and antiseptic procedures, and 0.5–1 mL of 5% dextrose solution was applied subcutaneously adjacent to the nerves at these points along the nerve path: anterior nerves: terminal branches of anterior femoral cutaneous nerve (Fig. 2a) and posterior nerve: posterior femoral cutaneous, a continuation of the inferior cluneal nerve (Fig. 2b). The injection was made at a 45-angle using a 27½-gauge (25 mm) needle, penetrating 15–20 mm through the skin. The number of injections varied according to the symptoms to be treated and ranged between 5 and 10 injections per session, with a mean of eight injections per knee per session. The patients were injected once a week for 6 weeks. After the first application of PIT, the patient was instructed to perform the physical therapy program as described above (thermotherapy, kinesiotherapy, and knee strengthening exercises) daily at home. All patients had a follow-up visit 6 months after the end of the treatment.

FIG. 2.

The knee nerve paths are marked in orange, and the painful points are marked in black. (A) Knee anterior nerve path (terminal branches of anterior femoral cutaneous nerve). (B) Knee posterior nerve path (posterior femoral cutaneous, a continuation of the inferior cluneal nerve).

Sample size

The authors hypothesized that pain intensity and WOMAC Index scores would decrease by 35% after PIT compared with the reduction after physical therapy alone. With an error of 0.05 and an error of 0.20, they calculated that a minimum of 22 patients and 44 knees would be needed for each group.

Measures

The primary measures of this study were the WOMAC index and a VAS for pain, and as a secondary measure the knee movement angles. VAS pain was evaluated by movement of the knees during clinical evaluation using a 0–10 scale, where 0 = no pain and 10 = the most pain experienced. After agreeing to participate in the study, patients were asked to stop the use of any type of analgesic to allow the authors to evaluate the response to pain as objectively as possible.

Statistical analysis

The statistical analysis was performed in two stages: descriptive and analytical. For descriptive statistics, the variables are presented as raw numbers, percentages, and means with standard deviations. For the analytical statistics, to identify differences between groups, the chi-squared test or Fisher's exact test was used for qualitative variables, and Student's t-test was used for quantitative variables. For between-group analysis, the same tests were used to compare results before and after treatment. A two-sided p-value <0.05 was considered to be significant. IBM SPSS for Windows (version 23; IBM Corp., Armonk, NY) was used.

Ethical considerations

The study was performed in accordance with the ethical norms of the Mexican Health Guidelines and the requirements established by the 1989 Declaration of Helsinki adopted by the General Assembly of the World Medical Association and the last amendment of Fortaleza Brazil in 2013. All patients provided written informed consent before entering the study. The distribution of patients was made using a closed-envelope system. The protocol was approved by the local Committee of Research and Ethics in Health (R-2017-1301-79). The protocol was registered at ClinicalTrials.gov (NCT03515720).

Results

This clinical trial was conducted from January through October 2017, and the follow up-period was conducted until May 2018, when the last patient included was submitted to evaluation. A total of 50 patients were recruited; 25 were assigned to the experimental group and 25 to the control group. The total numbers of kneecaps treated were 50 in the PT group and 49 in the PIT + PT group. A 61-year-old woman in the experimental group had received a total right knee replacement, and only her left knee was included in this study. The general characteristics of the groups and the pretreatment knee movement angles, WOMAC Index, and pain VAS are shown in Table 1. No differences in the basal characteristics of the study and control groups were observed.

Table 1.

General Characteristics of Patients in the Study and Control Groups and Western Ontario and McMaster Osteoarthritis Index, Pain Score (Visual Analog Scale), Flexion and Extension Movements Before Treatment with Physical Therapy with or without Perineural Injection Treatment

	Study group (n = 25)	Control group (n = 25)	p-Value
Age (years)	55.5 ± 14.8	53.5 ± 14.4	0.63
Sex
Male	7 (28%)	5 (20%)	0.5
Female	18 (72%)	20 (80%)	0.5
Activities
Homework	15 (60%)	12 (48%)	0.49
Employee	6 (24%)	7 (28%)
Retired	3 (12%)	3 (12%)
Others	1 (4%)	3 (12%)
Chondromalacia patella
II	6 (24%)	8 (32%)	0.53
III	19 (76%)	17 (68%)	0.53
Gonarthrosis
I	4 (16%)	3 (12%)	0.91
II	3 (12%)	3 (12%)
III	18 (72%)	19 (76%)
Use of a walking aid	6 (24%)	3 (12%)	0.5
WOMAC scale
WOMAC pain	11.2 ± 2.9	9.6 ± 3.3	0.07
WOMAC stiffness	4.2 ± 1.8	4.3 ± 1.3	0.86
WOMAC functional capacity	36.9 ± 9.9	32.5 ± 8.3	0.09
WOMAC total index (0–96)	51 ± 13.8	46.3 ± 12	0.21
VAS pain score	7.3 ± 1.5	7.0 ± 1.4	0.12

PIT, perineural injection treatment; VAS, visual analog scale; WOMAC Index, Western Ontario and McMaster Osteoarthritis Index.

Movement angles did not change significantly from before to after treatment. The mean number of injections per session was 8.51 ± 1.44 per patient. In the one patient in the PIT + PT group who received treatment for her left knee only, pain improved markedly from an initial VAS score of 7.5 to 2.3.

Table 2 shows the results of the between-group analysis. Some variables changed significantly after treatment in both groups. The after treatment mean between-group difference comparison can be found in Figure 3. No complications, such as bruising or infection, were observed during the procedure.

FIG. 3.

WOMAC Index and VAS score comparisons between groups. VAS, visual analog scale; WOMAC Index, Western Ontario and McMaster Osteoarthritis Index.

Table 2.

Between-Group Comparison of Western Ontario and McMaster Osteoarthritis Index, Pain Score (Visual Analog Scale), and Flexion and Extension Movements Before and After Treatment with Physical Therapy with or without Perineural Injection Treatment

	PIT + PT group (n = 25)			PT group (n = 25)			p-Value after treatment in study and control groups
	Before treatment	After treatment	Change score	Before treatment	After treatment	Change score	p-Value after treatment in study and control groups
WOMAC pain	11.2 ± 2.9	3.8 ± 2.2	7.3 ± 3.5	9.6 ± 3.3	6.3 ± 2.9	3.2 ± 2.9	<0.010
WOMAC stiffness	4.2 ± 1.8	1.1 ± 1.5	3 ± 1.69	4.3 ± 1.3	2.7 ± 1.8	1.6 ± 1.5	<0.010
WOMAC functional capacity	36.9 ± 9.9	13.7 ± 8.3	23.2 ± 10.7	32.5 ± 8.3	21.3 ± 9.5	11.1 ± 8.9	<0.010
WOMAC total	51 ± 13.8	17.8 ± 10.8	33.1 ± 15.6	46.3 ± 11.9	29.6 ± 12.1	16.7 ± 12.7	<0.001
VAS pain score	7.5 ± 1.6	2.3 ± 1.4	5.2 ± 2	7.0 ± 1.4	4.5 ± 1.6	2.5 ± 1.98	<0.001
Right side flexion	113.40 ± 9.9	115.5 ± 9.2	2.12 ± 3.51	111.6 ± 11.1	113.5 ± 9.6	1.92 ± 3.17	0.457
Left side flexion	113.3 ± 8.4	116.5 ± 9.3	3.20 ± 4.66	112.2 ± 11.4	114.8 ± 9.3	2.52 ± 3.53	0.520
Right side extension	−0.60 ± 1.6	−0.12 ± 0.6	0.48 ± 1.41	−1.16 ± 2.96	−0.40 ± 2	.76 ± 2.33	0.506
Left side extension	0.60 ± 1.6	−0.12 ± 0.6	0.48 ± 1.41	0.68 ± 1.6	0 ± 0	−0.68 ± 1.62	0.322

Flexion and extension angles were measured in degrees.

PIT, perineural injection treatment; VAS, visual analog scale; WOMAC Index, Western Ontario and McMaster Osteoarthritis Index.

Discussion

Knee pain is one of the main reasons for consulting a rehabilitation service, and patellofemoral chondromalacia associated with gonarthrosis is the principal cause. The results of this study were satisfactory for both the PIT + PT and PT groups; however, the responses to therapy were greater in patients in the PIT + PT groups in terms of WOMAC index scores and VAS pain scores. The authors found no evidence of complications, although the follow-up was short (6 months). There are few scientific reports of the evaluation of PIT; to knowledge, this is the first controlled clinical trial to be performed in Mexico. PIT showed a beneficial effect in pain reduction. The control of pain facilitates the patient's adherence to the rehabilitation program, which helps to improve joint mobility and facilitate the management of the main risk factors for chondromalacia and gonarthrosis.^20,21

The beneficial effects of perineural dextrose injection have been demonstrated in other randomized-controlled trials (RCT), although these studies used injections in different areas and at different doses.^22
–24 The results indicated rapid improvement and high levels of satisfaction in patients treated with PIT. These results showed favorable effects even at a lower concentration of dextrose. The authors are yet to identify another study that used 5% dextrose.

Because there is little information about the efficacy of extra-articular dextrose injections, some studies have compared the efficacy of PIT and DPT. For example, Farpour and Fereydooni²⁵ reported an RCT including 25 patients treated with two intra-articular infiltrations of hypertonic 25% dextrose and 25 patients infiltrated twice at painful points with subcutaneous 10% dextrose, and observed similar results in both groups for pain and WOMAC Index scores after follow-up. However, the methodology of the study and the sample size were insufficient to provide significant results. Another study by Rezasoltani et al.²⁶ included 104 people with knee osteoarthritis divided into two groups. One group of 54 patients received three intra-articular infiltrations of 10% dextrose, and another group of 50 patients received subcutaneous infiltrations of 20% dextrose into four painful points over the knee for three sessions with an interval of 1 week between each. Both groups showed a similar reduction in the main endpoint, VAS score for pain, after 5 months of follow-up. However, the treatment interval used in that study for the intra-articular injection was inappropriate, which could mean the results were skewed toward the periarticular application.

This study has some limitations. One limitation is the subjectivity and variability of the VAS for measuring the pain threshold for each patient. It would have been desirable to measure parameters of physical performance, such as muscle strength, maximum walking distance, and time with and without pain. It is difficult to quantify pain and the inflammatory response because evaluation of these in a single joint may not always provide reliable results in patients with comorbidities. It also would have been desirable to have included a placebo group in addition to the PT group. However, the use of placebos, such as transcutaneous or intramuscular infiltration of saline solution, is known to induce changes in the manifestations of acute and chronic pain, as observed in the control groups treated with saline infiltration, all of which showed some degree of improvement.²⁷ Another limitation could be the follow-up time, as the PIT+PT group was followed for 7.5 months, while the PT group was only followed for 6 months. Both groups reported to have a better outcome in pain and function; however, it is unclear if a longer follow-up could provide better results to the patients with only physical therapy. In addition, this study used a small sample, and these results could have incorporated a type I error. The authors encourage further studies to evaluate the benefit of this treatment option in addition to other methods of evaluating pain or function in larger clinical trials.

Conclusions

The injection of a 5% dextrose solution into the subcutaneous nerves as a treatment for patellofemoral chondromalacia associated with grade II or III gonarthrosis may be effective to treat knee pain and stiffness and restore functional capacity. This could be considered a pretreatment before surgical intervention or even before starting long-term pharmacologic treatment. PIT is a fast, effective, inexpensive, and minimally invasive therapy with only minor side effects such as sensitivity or bruising at the puncture site.

Footnotes

Authors' Contributions

S.A.G.-T. conceived the presented idea. M.F.T.-S., X.V.L.-G., and R.M.-P. contributed to the design and implementation of the research. PIT was performed by S.A.G.-T., M.F.T.-S., and X.V.L.-G. I.V.B.-P., I.E.-E., B.G.G.-R., K.J.P.-B., D.R.-N., and A.B.-H. assisted with the patient recruitment process. Data management and analysis were performed by F.J.B.-C., C.F.-O., and A.G.-O. All authors participated in the writing of the article. All authors read and approved the final article.

Acknowledgments

The authors of this article thank the participants of the study for their cooperation, and OnLine English for editing the article.

Author Disclosure Statement

All authors declare that they have no competing financial interests.

Funding Information

The authors received no financial support for the research, authorship, and publication of this article.

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