Journal of Pain Research Dovepress

open access to scientific and medical research

Open Access Full Text Article

C L I N I C A L T R I A L R E P O RT

Ultrasound-Guided Injection of High Molecular

Weight Hyaluronic Acid versus Corticosteroid in
Management of Plantar Fasciitis: A 24-Week
Randomized Clinical Trial
This article was published in the following Dove Press journal:
Journal of Pain Research

Seyed Ahmad Raeissadat 1,2 Background and Aims: Plantar fasciitis (PF) is the leading cause of heel pain in adults.
Farshad Nouri 2 This study was designed to evaluate the effect of hyaluronic acid (HA) injection in reducing
Mahtab Darvish 1,2 the symptoms of PF, compared with corticosteroid (CS) injection as a conventional
Hadi Esmaily 3 treatment.
Methods: In this triple-blind, randomized, clinical trial, 75 patients who had the symptoms
Parsa Ghazihosseini 1,2
of PF for at least 3 months were randomly divided into two groups of 38 and 37 individuals.
1
Clinical Research Development Center, Then, each patient received either a single injection of high molecular weight (>2000 kDa)
Shahid Modarres Hospital, Tehran, Iran;
2
Physical Medicine and Rehabilitation HA (1 mL HA 20 mg + 1 mL lidocaine 2%) or CS (1 mL methylprednisolone 40 mg + 1 mL
Research Center, Shahid Beheshti lidocaine 2%) under the ultrasonography (US) guidance. Visual analog scale (VAS), foot
University of Medical Sciences, Tehran,
ankle ability index (FAAI), pressure pain threshold (PPT), functional foot index (FFI), and
Iran; 3Department of Clinical Pharmacy,
School of Pharmacy, Shahid Beheshti plantar fascia thickness (PFT) were measured using US at baseline, 6 weeks and 24 weeks
University of Medical Sciences, Tehran, after the injection. Eventually, at the end of the treatment period, the patients’ satisfaction
Iran
was measured. Intention to treat analysis was used to assess the results.
Results: After 24 weeks of follow-up, results from 60 subjects were fully obtained; how-
ever, results of 73 patients included into intention to treat analysis in the sixth-week follow-
up. In both groups, VAS, PFT and FFI decreased, while FAAI and PPT increased signifi-
cantly (P <0.001). At the baseline and at the 24th-week, no significant difference between the
two groups was observed in any of the variables. However, a comparison between the
baseline and the sixth-week results shows a prominent decrease in PPT and PFT in the CS
group compared to the HA group (P = 0.004 and P = 0.011). Finally, there were no statistical
differences between the two groups in treatment satisfaction (P = 0.618).
Conclusion: Both CS and HA were effective modalities for PF and can improve pain and
function with no superiority in 24th-week follow-ups, although CS seems to have a faster
trend of improvement in the short term.
Correspondence: Mahtab Darvish
Keywords: plantar fasciitis, hyaluronic acid, pain, visual analog scale, patient satisfaction,
Physical Medicine and Rehabilitation
Research Center, Shahid Modarres ankle joint
Hospital, Saadat Abad St., Yadegare Imam
Highway, Tehran 1998734383, Iran
Tel/Fax +982122832343
Email [email protected] Introduction
Hadi Esmaily Plantar fasciitis (PF) is the leading cause of heel pain in adults. Nearly 1 million
Department of Clinical Pharmacy, School patients visit physicians for the diagnosis and management of PF symptoms
of Pharmacy, Shahid Beheshti University
of Medical Sciences, Niayesh Highway, each year.1 The prevalence of heel pain in public is 4–7% and about 80% of this
Valiasr Ave, Tehran 6153-14155, Iran is caused by PF.2 It is more prevalent among women versus men, in those aged
Tel +98 9121579064
Email [email protected] 45–64 years versus those aged 18–44 years, and in the obese versus those with

submit your manuscript | www.dovepress.com Journal of Pain Research 2020:13 109–121 109
DovePress © 2020 Raeissadat et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/
http://doi.org/10.2147/JPR.S217419
terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing
the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
Raeissadat et al Dovepress

a body mass index (BMI) of less than 25 kg/m2.2,3 PF can other researchers demonstrated that in patients with rotator
cause significant morbidity and activity limitations in the cuff tears, intra-articular injections of HA provide immediate
affected patients.4 Nonsurgical treatment options include clinical improvement compared with ESWT.33
rest, ice application, stretching, exercise, proper footwear, The aim of this clinical trial is to compare the out-
arch supports, orthotics, night splints, extracorporeal comes of local administration of HA with CS injections for
shockwave therapy (ESWT),5 anti-inflammatory agents, patients with chronic plantar fasciopathy.
and various injections including corticosteroid (CS), plate-
let-rich plasma (PRP),6,7 prolotherapy,8 autologous whole Methods & Materials
blood,9 botulinum toxin10 or ozone.11
Patients and Setting
CSs are the most common injection modality for PF.
The participants of this study were patients with signs and
Based on a Cochrane review, CS injections have tempor-
symptoms of PF who were referred to the Physical
ary effects for near 24 weeks.3 Some adverse effects
Medicine & Rehabilitation clinic of Shahid Modarres
associated with CS injection are plantar fascia rupture,
Hospital in Tehran from March 2017 to January 2019.
fat pad atrophy, lateral plantar nerve injury, and calcaneal
osteomyelitis.12,13
Hyaluronic acid (HA) injection has been used for many
Inclusion Criteria
Inclusion criteria of this study were aging between 25 and
musculoskeletal disorders including osteoarthritis of the
60, having clinical diagnosis of PF based on history and
knee,14 persistent shoulder pain,15 osteoarthritis of the tem-
physical examination for at least 3 months, and finally not
poromandibular joint,16 knee pain in rheumatoid arthritis
having responded to primary conservative managements
patients,17 and soft tissue and periarticular conditions such
such as rest, shoe insoles, conventional physical therapy,
as lateral epicondylitis and patellar tendinopathy.18,19
exercise therapy, and nonsteroidal anti-inflammatory drugs
Recently, Kumai and colleagues reported that a single injec-
(NSAIDs).
tion of HA is clinically effective for the treatment of PF.20
The plantar fascia is a thick aponeurosis with its origin
at the medial calcaneal tubercle. The arch of the foot is Exclusion Criteria
supported by this fascia. Excessive running or standing for Patients were excluded from the study if they had done
prolonged periods of time may cause an increased amount ESWT or received any injection for PF within the past 3
of tension along the plantar fascia which in turn makes months, had history of previous surgery for PF, had active
changes in the aponeurosis that can be either acute or bilateral PF, and had systemic inflammatory disease such
chronic. More recently, the term plantar fasciosis has as rheumatologic diseases, a history of vascular insuffi-
been used instead of PF to show that the inflammation is ciency and neuropathic heel pain, associated pathology
not the main cause of the pain.21 Histopathologic investi- involving the lower limb such as history of tarsal tunnel
gation showed fibrous tissue has more disorganization syndrome, effusion of the ankle indicating an intra-
rather than inflammation in PF, this finding is more likely articular disease, old-healed calcaneal fracture, retrocalca-
to what happened in degenerative tendinosis.22,23 neal bursitis, achilles tendinopathy, ankle osteoarthritis,
HA is a polysaccharide that can be found in the extra- and finally, any deformity of foot and ankle, including
cellular matrix of soft connective tissues and synovial pes planus or pes cavus. Other reasons for exclusion
fluid.24,25 It plays different roles in maintaining elasticity include pregnancy, uncontrolled diabetes mellitus, BMI
and viscosity of synovial fluid and integrity of connective >33, low back pain with radiation to lower limb, and
tissues such as joints.26 HA has been reported to alleviate the infection or local trauma near the injection site.
pain,27 inhibit cartilage deterioration,28 avoid tissue
adhesion,29 and inhibit the development of blood vessels Ethical Considerations
and sensory nerves.30 Yoshida and colleagues31 reported This trial was conducted in accordance with the
that in a rat tendinopathy model, HA was effective for pain Declaration of Helsinki; hence the process of the treatment
relief and partial repair of the patellar tendon. Wu et al32 also was explained to the patients. Once the physician assures
showed that in patients with tendinopathy of the long head that the patient completely agrees with the study protocol,
of biceps, HA decreases metalloproteinase-1 and −3 expres- the written consent form was signed or fingerprinted by
sions in tenocytes and would attenuate tendinopathy. Also, the patient. The institutional review board of Shahid

submit your manuscript | www.dovepress.com Journal of Pain Research 2020:13

110
DovePress
Dovepress Raeissadat et al

Beheshti University of Medical Sciences (SBUMS) agreed is better than palpation-guided injection because the latter
on the protocol of this study. The treatment carried a low provides better relief in pain (VAS scores) and control of
risk of adverse side effects and patients were advised that PFT by enhancing the accuracy of the injection site by
they can withdraw their participation at any time. Patients exact localization of the plantar fascia during the injection.
also had access to the project’s physician whenever they Kane et al claimed that the US-guided injection of four
experience injection-related infection or fibrosis, persistent heels with recalcitrant PF is highly effective.37
pain, and swelling, or any neuromuscular complications. In this study, the plantar fascia was examined with a 3- to
This study was approved by ethical community of SBUMS 12-MHz real-time linear-array transducer (Ecube7 US sys-
(code: IR.SBMU.MSP.REC.1397.403) and was registered tem (Alpinion, Seoul, Korea)) with the patient lying prone
in the Iranian Center of Clinical Trials (www.irct.ir) (code: with 90° of knee flexion and neutral ankle position. The
IRCT20130523013442N26). injection was performed under aseptic conditions using
a 22-gauge needle. Plantar fascia thickening of >4 mm
Randomization and Patients’ Enrolment and/or abnormal hypoechoic areas in plantar fascia were
A computer-generated block randomization method was targeted under the longitudinal plane of US-guidance.
used to assign participants with a 1:1 ratio to both groups. Figure 1 presents our injection practice. Also, the needle
It was presumed that participants were distributed almost was inserted through the medial heel along with the long-
equally with respect to gender and age in both intervention axis view (in-plane technique) toward the target area. Then,
and positive control groups.34 2 mL of HA or CS were injected using a peppering techni-
Group 1. (HA) A syringe containing 20 mg in 1 mL que, which involves a single skin portal followed by several
high-molecular-weight HA (>2000 kDa) with 2% concen- penetrations of the fascia. Patients were kept in the sitting
tration of non-animal origin (Viscor®; Nikan Teb Kimia position without moving their foot for 30 min after the
Pharmaceutical Co., Ltd., Tehran, Iran) and 1 mL injection. They were sent home with instructions to limit
Lidocaine 2% for a total of 2 mL volume in one syringe the use of the affected foot for approximately 72 h and to use
was used in this study. acetaminophen in case of pain. Moreover, they were taught
Group 2. (CS) The patients in this group receive 40 mg in to perform stretching exercises. It should be noted that the
1 mL methylprednisolone acetate (methylprednisolone acet- use of NSAIDs was not allowed.
ate, 40 mg\mL vial, DEPO-MEDROL®, PFIZER) and 1 mL
Lidocaine 2% for a total of 2 mL volume in one syringe.
Outcome Measures
Although CS and HA were filled in same shaped pre- Visual Analog Scale (VAS)
filled syringes, because of the physical differences (visc- Patients were asked to rate pain by marking a horizontally
osity of the solution) between treatments, accidental positioned 10-cm VAS with anchor points of “no pain” and
unblinding of the injector would be unpredictable; hence, “worst possible pain”. Patients were also asked to verbally
we decided not to include the physician who did the
injections in the investigation team, and effective blinding
of the assessment physician was achieved by the physical
separation of the injecting and assessment department and
by document control protocols. Patients and the physicians
performing the assessments were blinded to the groups.
Every prefilled syringe placed in a sealed envelope by
a nurse to cover the turbidity of the CS suspension.

Injection Technique
US is an accurate, reliable, and non-invasive technique for
measuring PF thickness, monitoring effects of different
interventions, and guiding therapeutic interventions in
patients with PF.35 It can visualize increases in thickness
of the plantar fascia, hypoechoic changes, perifascial fluid
collections, and calcaneal spur.36 The US-guided injection Figure 1 Ultrasound-Guided Injection Practice.

submit your manuscript | www.dovepress.com

Journal of Pain Research 2020:13 111
DovePress
Raeissadat et al Dovepress

Figure 2 The Consolidated Standards of Reporting Trials (CONSORT) diagram of the current study.

submit your manuscript | www.dovepress.com Journal of Pain Research 2020:13

112
DovePress
Dovepress Raeissadat et al

Table 1 Baseline Characteristics of the Participants in the Groups Table 3 Between Group Analysis of Outcomes Over the Time
a b
Variable HA CS P-value Time HAa CSb P-value

n 38 37 - Baseline
Age (year) 41.73 ± 7.68 40.33 ± 10.17 0.510 VASc 8.00 ± 1.35 7.72 ± 1.04 0.430
Gender (female:male) 18:20 22:15 0.293 FAAMd 46.65 ± 9.82 45.36 ± 6.39 0.508
Weight (kg) 77.00 ± 7.70 79.81 ± 6.41 0.096 PPTe 48.83 ± 7.84 46.71 ± 5.24 0.281
Body mass index (kg/m2) 27.01 ± 1.96 27.70 ± 1.43 0.092 USVf 49.57 ± 7.04 48.42 ± 4.85 0.465
FFIg 78.92 ± 14.34 74.46 ± 7.32 0.104
Job
Difficult employees 4 5 0.057 6 Weeks
Not difficult employees 19 16 VAS 3.05 ± 2.33 2.40 ± 2.16 0.222
Housewife 10 16 FAAM 65.27± 11.93 70.11 ± 12.97 0.103
Unemployed 5 0 PPT 57.51 ± 12.29 65.77 ± 11.52 0.004*
SID (right:left) 25:13 21:16 0.208 USV 45.95 ± 5.92 42.66 ± 4.66 0.011*
Duration of symptoms 7.30 ± 3.50 6.92 ± 3.63 0.650 FFI 33.73 ± 20.08 29.71 ± 15.89 0.352
(months)
24 Weeks
Notes: aHyaluronic Acid Injection Group. bCorticosteroid Injection Group VAS 3.24 ± 2.24 3.49 ± 1.93 0.625
FAAM 70.32± 14.96 67.29 ± 14.17 0.380
rate their pain “on a scale of 0 to 10“, with 0 indicating no PPT 61.74 ± 12.97 63.14 ± 14.52 0.696
USV 44.52 ± 5.90 43.76 ± 5.31 0.604
pain and 10 showing the worst possible pain.38
FFI 28.97 ± 22.85 31.93 ± 20.17 0.597
Satisfaction (3,2,7,15,10)h (3,3,12,11,7) 0.618
Pressure Pain Threshold (PPT) a
Notes: *P-values of <0.05 were considered significant. Hyaluronic Acid Injection
The PPT is a popular model for inducing acute, experi- Group. bCorticosteroid Injection Group. cVisual Analog Scale (mm). dFoot and
Ankle Ability Measure. ePressure Pain Threshold. fUltrasonography Thickness
mental pain.39 Algometry is a useful technique in deter- Values. gFunctional Foot Index. hCount: 1: Very Dissatisfied, 2: Dissatisfied, 3:
mining PPT measures that is used widely in both clinical Neutral, 4: Satisfied, 5: Very Satisfied.

and laboratory settings.40,41

Pressure algometry is mainly a manual procedure that measure the tenderness threshold (TT). It is a force
requires a perceptual response from the participant or gauge fitted with an elastic disc with a surface area of
patient.39 The results of previous studies have shown that 1 cm2 and is calibrated in kg/cm2. The algometer is
this test has very good measurement reliability, with intra- applied on the medial calcaneal tuberosity by placing the
class correlations (ICC) greater than 0.8 for the PPT mea- algometer at a 90° vertical angle to the skin surface. The
surements, which indicates that participants were indeed maximum pressure applied is up to 11 kg/cm2. If no pain
capable of judging their pain and discomfort thresholds.42 was recorded in the maximum pressure, the TT is defined
An analog algometer (SM100 Sundoo®) was used to as 11 kg/cm2. The minimum pressure to provoke pain was

Table 2 Within Group Analysis of Outcomes Over the Time

VASa FAAMb PPTc USVd FFIe

HAf
Baseline 8.00 ± 1.35 46.65 ± 9.82 48.83 ± 7.84 49.57 ± 7.04 78.92 ± 14.34
6 weeks 3.05 ± 2.33 65.27 ± 11.93 57.51 ± 12.29 45.95 ± 5.92 33.73 ± 20.08
24 weeks 3.24 ± 2.24 70.32 ± 14.96 61.74 ± 12.97 44.52 ± 5.90 28.97 ± 22.85
*P-value <0.001 <0.001 <0.001 <0.001 <0.001

CSg
Baseline 7.77 ± 1.06 45.36 ± 6.39 46.71 ± 5.24 48.42 ± 4.85 74.46 ± 7.32
6 weeks 2.40 ± 2.16 70.11 ± 12.97 65.77 ± 11.52 42.66 ± 4.66 29.71 ± 15.89
24 weeks 3.49 ± 1.93 67.29 ± 14.17 63.14 ± 14.52 43.76 ± 5.31 31.93 ± 20.17
*P-value <0.001 <0.001 <0.001 <0.001 <0.001
Notes: *P-values refer to changes over time within each treatment group, based on the Repeated Measures. P-values of <0.05 were considered significant. aVisual Analog
Scale. bFoot and Ankle Ability Measure. cPressure Pain Threshold. dUltrasonography Thickness Values. eFunctional Foot Index. fHyaluronic Acid Injection Group.
g
Corticosteroid Injection Group.

submit your manuscript | www.dovepress.com

Journal of Pain Research 2020:13 113
DovePress
Raeissadat et al Dovepress

Table 4 Comparing the Success Rate Between Groups Over the Ultrasonography Thickness Values (USV)
Time In clinical settings, USV is a very valuable diagnostic tool for
Time HA a
CS b
P-value detecting PF via direct observation of the thickness and
Success Rate ≥ 30%
echogenicity of the plantar fascia.46 USV assessment is rela-
VASc 29 25 0.304 tively fast, inexpensive, and widely available. It may detect
FAAMd 24 22 0.564 relatively small differences in plantar fascia even in clinically
PPTe 16 18 0.289 undetected cases.47 Increased thickness and hypo-
USVf 0 0 - echogenicity in plantar fascia are consistent sonographic
FFIg 27 23 0.322
findings in patients with PF. USV greater than 4 mm will
Success Rate ≥ 50% be considered as abnormal.46 PF does not affect the thickness
VAS 21 20 0.570 and echogenicity of the heel pad; therefore, USV may help to
FAAM 24 22 0.395
make a difference between heel pad pathologies and PF.47
PPT 8 11 0.232
Sabir et al48 suggested that US imaging could be as valuable
USV 0 0 -
FFI 23 19 0.326 as magnetic resonance image for detecting PF. The efficacy
Notes: Hyaluronic Acid Injection Group. Corticosteroid Injection Group. cVisual
a b of US imaging is often limited by examiner-dependent
Analog Scale. dFoot and Ankle Ability Measure. ePressure Pain Threshold. error.49 However, previous studies have shown the reprodu-
f
Ultrasonography Thickness Values. gFunctional Foot Index.
cibility of measurements of plantar fascia thickness by US,
with high intra-and inter-observer reliability.46,50 The exam-
ination of each plantar fascia included B-mode scanning was
written down. Then, the measurement was done three
performed using an Ecube 7 US system (Alpinion, Seoul,
times with 30-s intervals at the same location and the
Korea) with a 3–12-MHz linear transducer (L3-12H;
average value was recorded. Alpinion). All examinations were conducted by
a physiatrist. Each subject was examined lying prone with
Foot Function Index-Revised (FFI-R) 90° of knee flexion and neutral ankle position. In
The FFI-R is a 17-item questionnaire in which each item is a longitudinal view, the thickness of the plantar fascia was
scored on a 10-point Likert scale. FFI is used widely measured from the anterior edge of the inferior calcaneal
worldwide. This instrument that establishes a quantifiable border vertically to the inferior border of the plantar fascia.
measure of foot health has changed the approach of out- Finally, local or diffuse hypo-echogenicity at the calcaneal
come measurement to subjective, patient-centered, valid, insertion of the plantar fascia were evaluated.
reliable, and responsive hard data endpoints. Editing FFI-
R into four response categories will enhance its user- Satisfaction
friendliness for measuring foot health.43 Patients’ satisfaction was assessed at the end of the study
based on the Likert scale from 1 to 5 (1= Not satisfied at
Foot and Ankle Ability Measure (FAAM ADL) all, 5= Very satisfied).
The FAAM is a 29-item questionnaire divided into two
categories: activities of daily living (ADL) with 21 items Data Analysis
and SPORTS with 8 items.44 Each item is scored on The intention-to-treat (ITT) patients were defined as all
a 5-point Likert scale that represents different levels of included patients after randomization and before treatment
difficulty (no difficulty at all, slight difficulty, moderate commenced at 24-week follow-up. Statistical analysis of
difficulty, extreme difficulty and inability to do). The ADL data was performed using SPSS software version 22
and SPORTS subscales have a total score of 84 and 32, (SPSS Inc., Chicago, IL, USA). Chi-square (χ2) method
respectively. In this study, we used the Persian-translated and Fisher’s exact test were used to compare qualitative
version of FAAM that formerly was validated in a study data between groups. Student’s t-test and ANOVA were
by Mazaheri et al and showed good reliability and validity used for comparing quantitative data, within and between
for patients with foot and ankle musculoskeletal groups. Comparison of the pre- and post-treatment data
conditions.45 Because most of our patients were not ath- was done using paired t-test and repeated measurement
letes, we only use the ADL subgroup with a total score methods. The two-tailed p-values less than 0.05 were
of 84. considered as significant.

submit your manuscript | www.dovepress.com Journal of Pain Research 2020:13

114
DovePress
Dovepress Raeissadat et al

Figure 3 The visual analog scale (VAS) trend of changes in the hyaluronic acid (HA) and corticosteroid injection (CS) groups.

Results study, 40 patients (53.4%) were women and 35 (46.6%)

A total of 94 patients were initially enrolled, of which 75 were men with a mean age of 41.04 ± 8.96 years (22–60
were included in this study. Using a computer program for years). With respect to the difficulty level of the job, 9
random allocation, participants were randomly divided patients were categorized in difficult job group (12.0%),
into two parallel groups of CS and HA injection (38 in 26 were housewives (34.6%), 5 were unemployed (6.6%)
and 35 (46.6%) had jobs that were categorized as non-
the HA group and 37 in the CS group). However, within
difficult. The average BMI calculated as weight/(height)2
the time to 6-week follow-up, one patient in each group
was 27.01 ± 1.97 in HA group and 27.71 ± 1.44 kg/m2 in
lost to follow-up and four patients in the HA group and six
CS group. Mean duration of pain was 7.30 ± 3.50 (in
patients in the CS group discontinued the study due to lack
months) in HA group and 6.92 ± 3.64 in CS group.
of satisfactory efficacy despite the intervention (CS or HA)
As presented in Table 1, no significant difference was
and continuation of the bothersome PF pain. They were
observed in the two groups with respect to their demo-
eager to receive another intervention. These last patients’ graphic data including age, sex, height, weight, BMI, job
results recorded, and after excluding from the study, they difficulty, level of education and pain duration. Thus, we
received ESWT, physical therapy or CS injection depends could conclude that the population was homogeneously
on their first interventions. The endpoint results of these distributed in the groups.
patients included into ITT analysis. As a result, collected VAS, PPT, FFI, FAAM and plantar fascia thickness by
data from 60 patients including 29 participants in the CS US was measured at baseline, 6 weeks and 24 weeks after
group and 31 ones in the HA group were finally analyzed the intervention. Also, satisfaction based on the Likert
at 24-week time (CONSORT flow chart Figure 2). In this 5-point scale was measured in the 24th week.

submit your manuscript | www.dovepress.com

Journal of Pain Research 2020:13 115
DovePress
Raeissadat et al Dovepress

Figure 4 The pressure pain threshold (PPT) trend of changes in the hyaluronic acid (HA) and corticosteroid injection (CS) groups.

Table 2 summarizes the changes of the mean VAS, 51.6% vs 62.1% (P = 0.289), and FFI 87.1% vs 79.3%
PPT, FAAM, FFI, and USV within groups at baseline, 6 (P = 0.322). Table 4 compares success rates between the
weeks and 24 weeks after the treatment. It also showed the two groups.
mean satisfaction in each group at the end of the 24-week The VAS, PPT, USV, FFI and FAAM trend of changes
follow-up. At the baseline and the 24th week, no signifi- in plantar fascia thickness in the HA and the CS injection
cant difference was observed between the two groups for groups are shown in Figures 3–7.
any of the variables (P> 0.05). However, between baseline
and the sixth week, the increase in PPT and decrease in Discussion
plantar fascia USV was significantly higher in the CS To the best of our knowledge, this is the first study that
group compared to HA group (P = 0.004 and P = 0.011, compares the effects of US-guided injection of CS and HA
respectively). Table 3 compares the results between the in patients with chronic PF at 6 weeks and 24th-week
two groups over the time. follow-ups.
Participants’ satisfaction, measured at the end of the The results of this study show that there was no sig-
study, was relatively similar for both groups (P= 0.618). nificant difference between the two groups for VAS, PPT,
We defined success rates for both interventions as any FAAM, FFI and fascia thickness measured by the US
decrease in about 30% or higher from the baseline scores before treatment. However, 6 weeks after the treatment,
on the third assessment (24 weeks after intervention). plantar fascia thickness measured by US (P <0.001) and
According to this definition, success rates  30% for each PPT (P <0.001) became significantly better in the CS
scale are as follows (HA vs CS): VAS 93.5% vs 86.2% group compared to the HA group. Also, 24 weeks after
(P = 0.304), FAAM 77.4% vs 75.9% (P = 0.564), PPT the treatment, no significant difference between any

submit your manuscript | www.dovepress.com Journal of Pain Research 2020:13

116
DovePress
Dovepress Raeissadat et al

Figure 5 The ultrasonographic ultrasonography thickness values (USV) trend of changes in plantar fascia in the hyaluronic acid (HA) and corticosteroid injection (CS)
groups.

variable was observed in both groups. In this study, no of CS injection in the treatment of PF was evaluated. All
serious adverse events were seen in any of the groups. placebo-controlled randomized controlled trials (RCTs)
CS and HA were both effective treatments for PF and showed a significant reduction in pain with the use of CS
can improve pain and function with no superiority in 24- injections. However, it is evident from these studies that
week follow-up; however, CS seems to have a faster trend the effects of CS injections are usually short term, lasting
of improvement in the short term. only for a duration of 4–12 weeks.56
Steroid injection is commonly used to treat PF. There is Kumai et al20 evaluated the efficacy of high molecular
some evidence that injected CS were effective in providing weight HA (H-HA), low molecular weight HA (L-HA)
transitory pain relief.51 The rapid effects of steroid injec- and a 0.01% HA (control group) injections in the treatment
tion on pain inspire its common use in treating PF. of recalcitrant PF. Patients were evaluated at baseline and
However, current scientific evidence shows that steroid 5 weeks after injection. Based on the obtained results, the
injection should be avoided in treating PF in athletes improvement in the VAS score for pain in patients with PF
because of its greater risk of causing spontaneous was significantly greater in the H-HA group than in the
ruptures.52 control group. More noticeable improvement was achieved
The efficacy of CS in treating chronic inflammation has in the H-HA group compared with the L-HA group. Other
been well demonstrated.53,54 Intralesional injection of CS measures such as Roles and Maudsley score, local symp-
in chronic PF (defined as persistence of symptoms more toms, and FAAM, were also improved in each group, with
than 8 weeks despite conservative care) has been shown to the H-HA group having better results. Outcomes were also
be effective.55 In a review by Ang TW,56 the effectiveness improved by an injection of 0.01% HA (control group);

submit your manuscript | www.dovepress.com

Journal of Pain Research 2020:13 117
DovePress
Raeissadat et al Dovepress

Figure 6 The functional foot index (FFI) trend of changes in the hyaluronic acid (HA) and corticosteroid injection (CS) groups.

therefore, the injection itself may have possible improve- patients. Although our follow-up was for 24 weeks, longer
ment in pain and FAAM. follow-ups and assessing the recurrence rate of PF would
In summary, it can be stated that HA may be a proper be recommended in upcoming studies.
choice for treating PF. These findings, like our study, In this study, we used a single injection of 20 mg high-
showed the effectiveness of high molecular weight HA molecular-weight, linear HA (>2000 kDa) of non-animal
in the improvement of pain and function of patients with origin in 1 mL (Viscor® 2%; Nikan Teb Kimia
chronic PF. Pharmaceutical Co., Ltd., Tehran, Iran). Based on the
So far, only one other study has been conducted to eval- brand of the HA and its properties such as molecular weight,
uate a single HA injection in the treatment of chronic PF. concentration, linear or reticulated HA, different results may
Advantages of this study were using different outcome be achieved, and the results of this study may not be general-
measures including VAS, FAAM, FFI, and PPT and mea- izable to other HA products. Investigating the molecular
suring changes of plantar fascia thickness by US. Also, weight effect and dose response on the efficacy of HA in
US-guided injection had the advantage of more precisely PF would be a research target for future studies. Another
localizing the exact site of injection and doing the inter- limitation of this study is that no economic analysis between
vention with more accuracy. two injections was directed in our trial.
For future studies, we recommend evaluating the effi-
cacy of HA injection in special groups such as athletes Conclusion
with higher risk of plantar fascia rupture due to CS injec- Both corticosteroid and hyaluronic acid are effective
tion. Also, it is recommended enrolling larger number of interventions for plantar fasciitis and can improve pain

submit your manuscript | www.dovepress.com Journal of Pain Research 2020:13

118
DovePress
Dovepress Raeissadat et al

Figure 7 The foot and ankle ability measure (FFAM) trend of changes in the hyaluronic acid (HA) and corticosteroid injection (CS) groups.

and function with no superiority in 24-week follow-up,

although corticosteroid seems to have a faster trend of References
improvement in the short term. No serious adverse 1. Riddle DL, Schappert SM. Volume of ambulatory care visits and
patterns of care for patients diagnosed with plantar fasciitis:
effects were seen in any groups.
a national study of medical doctors. Foot Ankle Int.
2004;25:303–310. doi:10.1177/107110070402500505
Data Sharing Statement 2. Beeson P. Plantar fasciopathy: revisiting the risk factors. Foot Ankle
Surg. 2014;20:160–165. doi:10.1016/j.fas.2014.03.003
The authors intend to share participants' data collected 3. David JA, Sankarapandian V, Christopher PRH, Chatterjee A,
during the trial, after deidentification. This includes, Macaden AS. Injected corticosteroids for treating plantar heel pain in
adults. Cochrane Database Syst Rev. 2017. doi:10.1002/14651858.
study protocol, statistical analysis plan, informed consent
CD009348.pub2
forms, clinical study report, and analytic code. It will be 4. Roerdink RL, Dietvorst M, van der Zwaard B, der Worp H, Zwerver J.
available based on the request of investigators whose Complications of extracorporeal shockwave therapy in plantar fascii-
tis: systematic review. Int J Surg. 2017;46:133–145. doi:10.1016/j.
proposed use of the data has been approved by an inde- ijsu.2017.08.587
pendent review committee by sending an email to the 5. Vahdatpour B, Mokhtarian A, Raeissadat SA, et al. Enhancement of
corresponding author. Data are available immediately the effectiveness of extracorporeal shock wave therapy with topical
corticosteroid in treatment of chronic plantar fasciitis: a randomized
after publication and with no end date. control clinical trial. Adv Biomed Res. 2018;7.
6. Singh P, Madanipour S, Bhamra JS, Gill I. A systematic review and
meta-analysis of platelet-rich plasma versus corticosteroid injections
Disclosure for plantar fasciopathy. Int Orthop. 2017;41:1169–1181. doi:10.1007/
The authors report no conflicts of interest in this work. s00264-017-3470-x

submit your manuscript | www.dovepress.com

Journal of Pain Research 2020:13 119
DovePress
Raeissadat et al Dovepress

7. Raeissadat SA, Babaee M, Rayegani SM, et al. An overview of 27. Tamoto K. High molecular weight hyaluronic acids inhibit
platelet products (PRP, PRGF, PRF, etc.) in the Iranian studies. interleukin-1-induced prostaglandin E_2 generation and prostaglan-
Futur Sci OA. 2017;3:FSO231. doi:10.4155/fsoa-2017-0045 din E_2-elicited cyclic AMP accumulation in human rheumatoid
8. Kim E, Lee JH. Autologous platelet-rich plasma versus dextrose arthritic synovial cells. Jpn J Rheumatol. 1994;5:227–236.
prolotherapy for the treatment of chronic recalcitrant plantar 28. Kikuchi T. Effects of hyaluronan on proteoglycan metabolism of
fasciitis. PM&R. 2014;6:152–158. doi:10.1016/j.pmrj.2013.07.003 rabbit articular chondrocytes in culture. Jpn J Rheumatol.
9. Karimzadeh A, Raeissadat SA, Erfani Fam S, Sedighipour L, Babaei- 1994;3:207–215.
Ghazani A. Autologous whole blood versus corticosteroid local 29. Weiss C, Levy HJ, Denlinger J, Suros JM, Weiss HE. The role of
injection in treatment of plantar fasciitis: a randomized, controlled Na-hylan in reducing postsurgical tendon adhesions. Bull Hosp Jt Dis
multicenter clinical trial. Clin Rheumatol. 2017;36:661–669. Orthop Inst. 1986;46:9–15.
doi:10.1007/s10067-016-3484-6 30. Tang T, Muneta T, Sekiya I. Fibrous change of the infrapatellar fat
10. Díaz-Llopis IV, Rodriguez-Ruiz CM, Mulet-Perry S, et al. pad due to strenuous running exercise and its treatment with intraar-
Randomized controlled study of the efficacy of the injection of ticular hyaluronan injection in a rat model. J Med Dent Sci.
botulinum toxin type A versus corticosteroids in chronic plantar 2008;55:163–173.
fasciitis: results at one and six months. Clin Rehabil. 31. Yoshida M, Funasaki H, Kubota M, Marumo K. Therapeutic effects of
2012;26:594–606. doi:10.1177/0269215511426159 high molecular weight hyaluronan injections for tendinopathy in a rat
11. Bahrami MH, Raeissadat SA, Barchinejad M, Elyaspour D, Rahimi- model. J Orthop Sci. 2015;20:186–195. doi:10.1007/s00776-014-0650-z
Dehgolan S. Local ozone (O2-O3) versus corticosteroid injection 32. Wu P-T, Kuo LC, Su FC, et al. High-molecular-weight hyaluronic acid
efficacy in plantar fasciitis treatment: a double-blinded RCT. J Pain attenuated matrix metalloproteinase-1 and −3 expression via CD44 in
Res. 2019;12:2251–2259. doi:10.2147/JPR.S202045 tendinopathy. Sci Rep. 2017;7:40840. doi:10.1038/srep40840
12. Acevedo JI, Beskin JL. Complications of plantar fascia rupture asso- 33. Frizziero A, Vittadini F, Barazzuol M, et al. Extracorporeal shock-
ciated with corticosteroid injection. Foot Ankle Int. 1998;19:91–97. waves therapy versus hyaluronic acid injection for the treatment of
doi:10.1177/107110079801900207 painful non-calcific rotator cuff tendinopathies: preliminary results.
13. Tahririan MA, Motififard M, Tahmasebi MN, Siavashi B. Plantar J Sports Med Phys Fitness. 2017;57:1162–1168. doi:10.23736/
fasciitis. J Res Med Sci. 2012;17:799–804. S0022-4707.16.06408-2
14. Petrella RJ, Petrella M. A prospective, randomized, double-blind, pla- 34. Vahdatpour B, Kianimehr L, Moradi A, Haghighat S. Beneficial
cebo controlled study to evaluate the efficacy of intraarticular hyaluronic effects of platelet-rich plasma on improvement of pain severity and
acid for osteoarthritis of the knee. J Rheumatol. 2006;33:951–956. physical disability in patients with plantar fasciitis: a randomized
15. Moskowitz RW, Blaine TA. An overview of treatment options for trial. Adv Biomed Res. 2016;5:179. doi:10.4103/2277-9175.192731
persistent shoulder pain. Am J Orthop (Belle Mead. NJ). 35. Mohseni-Bandpei MA, Nakhaee M, Mousavi ME, et al. Application
2005;34:10–15. of ultrasound in the assessment of plantar fascia in patients with
16. Iturriaga V, Bornhardt T, Manterola C, Brebi P. Effect of hyaluronic plantar fasciitis: a systematic review. Ultrasound Med Biol.
acid on the regulation of inflammatory mediators in osteoarthritis of 2014;40:1737–1754. doi:10.1016/j.ultrasmedbio.2014.03.001
the temporomandibular joint: a systematic review. Int J Oral 36. DiMarcangelo MT, Yu TC. Diagnostic imaging of heel pain and
Maxillofac Surg. 2017;46:590–595. doi:10.1016/j.ijom.2017.01.014 plantar fasciitis. Clin Podiatr Med Surg. 1997;14:281–301.
17. Matsuno H, Yudoh K, Kondo M, Goto M, Kimura T. Biochemical 37. Kane D, Greaney T, Bresnihan B, Gibney R, FitzGerald O.
effect of intra-articular injections of high molecular weight hyalur- Ultrasound guided injection of recalcitrant plantar fasciitis. Ann
onate in rheumatoid arthritis patients. Inflamm Res. 1999;48:154–159. Rheum Dis. 1998;57:383–384. doi:10.1136/ard.57.6.383
doi:10.1007/s000110050439 38. Bijur PE, Latimer CT, Gallagher EJ Validation of a verbally administered
18. Muneta T, Koga H, Ju Y-J, Mochizuki T, Sekiya I. Hyaluronan numerical rating scale of acute pain for use in the emergency department.
injection therapy for athletic patients with patellar tendinopathy. Available from: www.aemj.org. Accessed December 27, 2019.
J Orthop Sci. 2012;17:425–431. doi:10.1007/s00776-012-0225-9 39. Chesterton LS, Sim J, Wright CC, Foster NE. Interrater reliability of
19. Petrella RJ, Cogliano A, Decaria J, Mohamed N, Lee R. Management algometry in measuring pressure pain thresholds in healthy humans,
of Tennis Elbow with sodium hyaluronate periarticular injections. using multiple raters. Clin J Pain. 2007;23:760–766. doi:10.1097/
BMC Sports Sci Med Rehabil. 2010;2:4. doi:10.1186/1758-2555-2-4 AJP.0b013e318154b6ae
20. Kumai T, Samoto N, Hasegawa A, et al. Short-term efficacy and 40. Isselée H, De Laat A, Bogaerts K, Lysens R. Short-term reproduci-
safety of hyaluronic acid injection for plantar fasciopathy. Knee bility of pressure pain thresholds in masticatory muscles measured
Surgery Sport Traumatol Arthrosc. 2018;26:903–911. doi:10.1007/ with a new algometer. J Orofac Pain. 1998;12.
s00167-017-4467-0 41. Fischer AA. Pressure threshold measurement for diagnosis of myo-
21. Thomas JL, Christensen JC, Kravitz SR, et al. The diagnosis and fascial pain and evaluation of treatment results. Clin J Pain.
treatment of heel pain: a clinical practice guideline–revision 2010. 1986;2:207–214. doi:10.1097/00002508-198612000-00001
J Foot Ankle Surg. 2010;49:S1–S19. doi:10.1053/j.jfas.2010.01.001 42. Xiong S, Goonetilleke RS, Jiang Z. Pressure thresholds of the human
22. MacAuley D, Best TM. Evidence-Based Sports Medicine. Wiley foot: measurement reliability and effects of stimulus characteristics.
Online Library; 2007. Ergonomics. 2011;54:282–293. doi:10.1080/00140139.2011.552736
23. Schwartz EN, Su J. Plantar fasciitis: a concise review. Perm J. 43. Budiman-Mak E, Conrad KJ, Mazza J, Stuck RM. A review of the
2014;18:e105–7. doi:10.7812/TPP/13-113 foot function index and the foot function index – revised. J Foot
24. Nakamura H, Gotoh M, Kanazawa T, et al. Effects of corticosteroids Ankle Res. 2013;6:5. doi:10.1186/1757-1146-6-5
and hyaluronic acid on torn rotator cuff tendons in vitro and in rats. 44. Martin RL, Irrgang JJ, Burdett RG, Conti SF, Van Swearingen JM.
J Orthop Res. 2015;33:1523–1530. doi:10.1002/jor.22921 Evidence of Validity for the Foot and Ankle Ability Measure
25. Laurent TC, Fraser JR. Hyaluronan. FASEB J. 1992;6:2397–2404. (FAAM). Foot Ankle Int. 2005;26:968–983. doi:10.1177/
doi:10.1096/fasebj.6.7.1563592 107110070502601113
26. Chen LH, Xue JF, Zheng ZY, et al. Hyaluronic acid, an efficient 45. Mazaheri M, Salavati M, Negahban H, et al. Reliability and validity
biomacromolecule for treatment of inflammatory skin and joint dis- of the Persian version of Foot and Ankle Ability Measure (FAAM) to
eases: a review of recent developments and critical appraisal of measure functional limitations in patients with foot and ankle
preclinical and clinical investigations. Int J Biol Macromol. disorders. Osteoarthritis Cartilage. 2010;18:755–759. doi:10.1016/j.
2018;116:572–584. doi:10.1016/j.ijbiomac.2018.05.068 joca.2010.03.006

submit your manuscript | www.dovepress.com Journal of Pain Research 2020:13

120
DovePress
Dovepress Raeissadat et al

46. Cheng J-W, Tsai W-C, Yu T-Y, Huang K-Y. Reproducibility of sono- 52. Lee HS, Choi YR, Kim SW, et al. Risk factors affecting chronic
graphic measurement of thickness and echogenicity of the plantar rupture of the plantar fascia. Foot Ankle Int. 2014;35:258–263.
fascia. J Clin Ultrasound. 2012;40:14–19. doi:10.1002/jcu.v40.1 doi:10.1177/1071100713514564
47. Karabay N, Toros T, Hurel C. Ultrasonographic evaluation in plantar 53. journal, T. A.-S. Medical & 2015, undefined. The effectiveness of
fasciitis. J Foot Ankle Surg. 2007;46:442–446. doi:10.1053/j. corticosteroid injection in the treatment of plantar fasciitis. Available
jfas.2007.08.006 from: ncbi.nlm.nih.gov. Accessed December 27, 2019.
48. Sabir N, Demirlenk S, Yagci B, Karabulut N, Cubukcu S. Clinical 54. Foster ZJ, Voss TT, Frimodig A. Corticosteroid Injections for
utility of sonography in diagnosing plantar fasciitis. J Ultrasound Common Musculoskeletal Conditions. Vol. 92; 2015. Available
Med. 2005;24:1041–1048. doi:10.7863/jum.2005.24.8.1041 from: www.aafp.org/afp. Accessed December 27, 2019.
49. Scheel AK, Schmidt WA, Hermann KA, et al. Interobserver reliabil- 55. Mahindra P, Yamin M, Selhi HS, Singla S, Soni A. Chronic plantar
ity of rheumatologists performing musculoskeletal ultrasonography: fasciitis: effect of platelet-rich plasma, corticosteroid, and placebo.
results from a EULAR “Train the trainers” course. Ann Rheum Dis. Orthopedics. 2016;39:e285–e289. doi:10.3928/01477447-201602
2005;64:1043–1049. doi:10.1136/ard.2004.030387 22-01
50. Rathleff MS, Moelgaard C, Olesen JL. Intra-and interobserver relia- 56. Hsiao M-Y, Hung CY, Chang KV, et al. Comparative effectiveness
bility of quantitative ultrasound measurement of the plantar fascia. of autologous blood-derived products, shock-wave therapy and
J Clin Ultrasound. 2011;39:128–134. doi:10.1002/jcu.20787 corticosteroids for treatment of plantar fasciitis: a network
51. Crawford F, Thomson CE. Interventions for treating plantar heel meta-analysis. Rheumatology. 2015;54:1735–1743. doi:10.1093/
pain. In: Crawford F, editor. Cochrane Database of Systematic rheumatology/kev010
Reviews. John Wiley & Sons, Ltd;2003. doi:10.1002/14651858.
CD000416

Journal of Pain Research Dovepress

Publish your work in this journal
The Journal of Pain Research is an international, peer reviewed, open management system is completely online and includes a very quick
access, online journal that welcomes laboratory and clinical findings in and fair peer-review system, which is all easy to use. Visit http://
the fields of pain research and the prevention and management of pain. www.dovepress.com/testimonials.php to read real quotes from pub-
Original research, reviews, symposium reports, hypothesis formation lished authors.
and commentaries are all considered for publication. The manuscript
Submit your manuscript here: https://www.dovepress.com/journal-of-pain-research-journal

submit your manuscript | www.dovepress.com

Journal of Pain Research 2020:13 121
DovePress