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© 2019 EDIZIONI MINERVA MEDICA European Journal of Physical and Rehabilitation Medicine 2019 August;55(4):472-9
Online version at http://www.minervamedica.it DOI: 10.23736/S1973-9087.19.05432-7

ORIGINAL ARTICLE

Efficacy of intradermal administration of diclofenac

for the treatment of nonspecific chronic low back pain:
results from a retrospective observational study
Gianpaolo RONCONI 1 *, Giorgio FERRIERO 2, Cristina NIGITO 1,
Calogero FOTI 3, Giulio MACCAURO 4, Paola E. FERRARA 1

1Unit of Physical Medicine and Rehabilitation, Teaching Hospital Foundation “Agostino Gemelli”, IRCCS, Rome, Italy; 2Istituti Clinici
Scientifici Maugeri, IRCCS, Pavia, Italy; 3Department of Physical Medicine and Rehabilitation, Clinical Sciences and Translational
Medicine, Tor Vergata University, Rome, Italy; 4Orthopedic and Traumatology Institute, Catholic University of the Sacred Heart, Rome, Italy
*Corresponding author: Gianpaolo Ronconi, Policlinico Gemelli, Largo Agostino Gemelli 1, 00168 Rome, Italy.
E-mail: gianpaolo.ronconi@policlinicogemelli.it

ABSTRACT
BACKGROUND: Intradermal administration of analgesic drugs with mesotherapy is effective for the local treatment of musculoskeletal pain.
Few studies analyzed the effects of different drugs administrated with this technique.
AIM: The aim of this study was to compare the efficacy of diclofenac versus lysine acetylsalicylate-based mesotherapy in relieving pain (primary
outcome), and disability (secondary outcome) in patients with nonspecific chronic low back pain.
DESIGN: Retrospective observational study.
SETTING: Outpatient rehabilitation medicine center.
POPULATION: Records of 101 patients with nonspecific chronic low back pain.
METHODS: Data were extracted from the outpatients records of patients affected by nonspecific chronic low back pain since 12 weeks before,
treated with 5 sessions of mesotherapy with diclofenac mixtures (group A) or aspirin-lysine acetylsalicylate mixture (group B). Assessments
recorded were taken before the first treatment (T0), at the end of the 5-week treatment (T1), and at 4 (T2) and 12 weeks (T3) of follow-up after
the last treatment, using a pain visual analogue scale (VAS) primary outcome, Oswestry Disability Index (ODI) secondary outcome, and the
Short-Form McGill Pain Questionnaire (SF-MPQ) Comparisons within and between groups were performed using the t-test, the χ2 test, and
analysis of variance (ANOVA) models, as appropriate.
RESULTS: Records from 101 patients consecutively were analyzed, 51 in group A (mean age and standard deviation [SD]=62.8±10.7; F/
M=33/18) and 50 in group B (mean age±SD=64.1±15.8; F/M=30/20). At baseline VAS, SF-MPQ, ODI scores were respectively 7.6±1.3,
22.49±9.96, 44.80±15.55 (mean and SD) in group A; VAS, SF-MPQ, ODI scores were respectively 6.7±1.6, 18.66±9.65, 39.04±16.06 (mean
and SD) in group B. Mean differences between group A and group B in the changes of scores from baseline (T0) to end of study (T3) were -1.3
(VAS), -5.81 (SF-MPQ) and -17.05 (ODI). Mesotherapy induced significant reductions in pain severity and disability in both groups with better
results in diclofenac-based treatment.
CONCLUSIONS: This retrospective pilot study suggests the efficacy and safety of diclofenac mesotherapy for relieving pain and disability in
patients affected by chronic nonspecific low back pain in a convenient sample but further studies will confirm these results.
CLINICAL REHABILITATION IMPACT: Diclofenac mesotherapy appears to be a viable treatment. to reduce pain and improve function in
patients affected by chronic moderate-to-severe nonspecific low back pain.
(Cite this article as: Ronconi G, Ferriero G, Nigito C, Foti C, Maccauro G, Ferrara PE. Efficacy of intradermal administration of diclofenac for
the treatment of nonspecific chronic low back pain: results from a retrospective observational study. Eur J Phys Rehabil Med 2019;55:472-9. DOI:
10.23736/S1973-9087.19.05432-7)
Key words: Rehabilitation; Spine; Injections, intradermal; Mesotherapy.

L ow back pain is a very common symptom and a

leading cause of years lived with disability world-
wide.1, 2 For most people presenting with low back pain it
is not possible to identify the specific nociceptive source.
Known causes of severe persistent low back pain include
malignancy, vertebral fracture, infections, and chronic in-

472 European Journal of Physical and Rehabilitation Medicine August 2019

 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access
COPYRIGHT 2019 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
DICLOFENAC FOR NONSPECIFIC CHRONIC LOW BACK PAIN RONCONI
flammatory diseases, but these account for less than 1% of
cases.3 Most episodes of low back pain improve substan-
tially within 6 weeks, but recurrence is common.4, 5 It is
estimated that approximately one-third of people with an
episode of low back pain will have a recurrence within 1
year from episode resolution.6
Nonspecific chronic low back pain is seen as major pub-
lic health problems worldwide that is not attributable to a
recognizable, specific pathology, with pain that lasts more
than 3 months before. Close to 12% of the population is
disabled by pain and its lifetime prevalence is as high as
84%, whereas the lifetime prevalence of chronic low back
pain is about 23%.7
Compared with past recommendations, current guide-
lines for the treatment of chronic nonspecific low back
pain place a greater emphasis on self-management, physi-
cal and psychological therapies, and complementary
medicine.8-10 Pharmacological treatment is recommended
only following an inadequate response to first-line non-
pharmacological interventions and is generally based on
non-steroidal anti-inflammatory drugs (NSAIDs), which
should be prescribed at the lowest effective dose and for
the shortest possible time.8
Mesotherapy has attracted interest, especially in Eu-
rope, as a possible treatment for musculoskeletal pain in-
cluding low back pain.11-16This minimally invasive tech-
nique involves the intradermal administration of analgesic
drugs through a series of injections into the superficial lay-
ers of the skin, resulting in a slower diffusion of the drug
compared with subcutaneous or intramuscular administra-
tion. In 84 patients with acute low back pain, intradermal
administration of NSAIDs and corticosteroids via meso-
therapy was compared with conventional systemic anti-
inflammatory therapy with NSAIDs and corticosteroids.12
Pain intensity and functional disability were significantly
improved in both groups, with no significant differences
between mesotherapy and systemic administration, de-
spite the markedly lower amount of drugs administered
via the mesotherapy technique. A formulation of inject-
able diclofenac complexed with β-cyclodextrin (Akis®,
IBSA Farmaceutici, Lody, Italy) has been developed for
subcutaneous and intramuscular use. The recently intro-
duced preparation has shown efficacy in relieving the pain
associated with knee osteoarthritis and spondyloarthrosis
when administered as mesotherapy.17-20 The increased
solubility of diclofenac in complex with β-cyclodextrin al-
lows significantly smaller volumes of analgesic solution to
be administered, compared with conventional approaches.
However, it has never been investigated the intradermal
Vol. 55 - No. 4 European Journal of Physical and Rehabilitation Medicine 473
efficacy of a specific drug as diclofenac compared with
another, as lysine acetylsalicylate, usually injected in the
treatment of localized pain.
We report here the results of a retrospective analy-
sis investigating the analgesic and functional efficacy of
diclofenac-based mesotherapy using the novel diclofenac
formulation compared with lysine acetylsalicylate-based
mesotherapy in patients with nonspecific chronic low back
pain.
Materials and methods
Study design and patient population
This was a retrospective observational study conducted to
investigate the efficacy of mesotherapy with diclofenac on
pain intensity (primary outcome) and disability (secondary
outcome) in patients with nonspecific chronic low back
pain. Chronic low back pain was defined as an episode
of low back pain lasting for 12 weeks or more.9 When no
cause can be identified, after the diagnostic triage using
history taking, physical examination, neurological testing
to identify radicular pain/radiculopathy, radiologic routine
imaging unless serious pathology low-back pain was clas-
sified as nonspecific or idiopathic.21 Data were extracted
from the consecutive records of patients treated with me-
sotherapy between January 2014 and July 2016 at a center
of rehabilitation medicine in Italy (unit of Physical Medi-
cine and Rehabilitation, Teaching Hospital Foundation
“Agostino Gemelli”, Catholic University of Sacred Heart,
Rome, Italy). The study was approved by the ethics com-
mittee of the institution (protocol number: 33220/16, ID:
11206) and conducted in accordance with the tenets of the
Declaration of Helsinki and the STROBE Statement for
reporting of observational studies.
Patients were included in the analysis if the following
inclusion criteria were met: considering age >18 years
presence of chronic low back pain lasting for 12 weeks or
more with no cause identified after a complete evaluation
including a detailed medical history, report of any allergic
reactions to anesthetics, routine physical examination and
a neurological investigation. The physical examination
of the lumbar spine was conducted by a doctor who was
unaware of the group allocation. All patients were asked
to provide a standard radiography (anterior-posterior and
lateral X-rays) of the lumbosacral tract: intensity of low
back pain >5 cm on a 10 cm visual analog scale (VAS); no
previous treatment with mesotherapy; no other pharmaco-
logical, physical, or exercise-based treatment administered
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access
COPYRIGHT 2019 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
RONCONI DICLOFENAC FOR NONSPECIFIC CHRONIC LOW BACK PAIN
during mesotherapy and until 3 months of follow-up after
the end of mesotherapy. Exclusion criteria were presence
of neurologic diseases or psychiatric disorders, vertebral
fractures, severe rheumatic disease, oncologic diseases.
Patients who had undergone surgical interventions were
also excluded, and the use of NSAIDs during mesotherapy
and up to 3 months following treatment was an additional
exclusion criterion.
Mesotherapy was administered by the same physiatrist
according to current treatment guidelines.22 All patients
signed informed consent before initiating treatment, as
recommended by current guidelines formulated by the
Italian Society of Mesotherapy.23 Patients received two
mesotherapy sessions per week for a total of five meso-
therapy sessions. In each session, patients were injected
with either 2 mL of a drug mixture containing 0.5 mL of
sodium diclofenac (Akis®, IBSA Farmaceutici Italia, 50
mg/mL) plus 0.5 mL of lidocaine hydrochloride 2% and 1
mL of physiological saline solution (group A), or 2 mL of
a drug mixture containing 0.5 mL of lysine acetylsalicylate
(Flectadol®, Sanofi S.p.A., Milan, 500 mg/2.5 mL) plus
0.5 mL of lidocaine hydrochloride 2% and 1 mL of physi-
ological saline solution (group B). The choice of the use
of different drug depended on the availability in the clinic
and was based on the physician clinical judgment. It was
used a point by point injecting technique in trigger and
tender low back point according to Travell et al.24
Data analysis
Data extracted from the patients records included demo-
graphic and clinical characteristics at baseline (T0, pre-
sentation at the center and initiation of mesotherapy); pain
intensity assessed with two different tools at T0, T1 (end
of 5 mesotherapy sessions), T2 (1-month follow-up) and
T3 (3-month follow-up); and disability scores at the same
time points. Pain was assessed using a VAS Score from 0
cm = no pain at all to 10 cm = worst pain imaginable,25 and
the Short-Form-McGill Pain Questionnaire (SF-MPQ).26
VAS scores ≤3.4 cm are generally described as mild pain,
3.5 to 6.4 cm as moderate pain, and ≥7.5 cm as severe
pain for patients with chronic musculoskeletal pain. The
SF-MPQ contains 15 descriptors, 11 sensory and 4 affec-
tive, rated on an intensity scale as 0 = none, 1 = mild, 2 =
moderate, and 3 = severe; the maximum score is 45.
Disability due to low back pain was evaluated using
the validated Italian translation of the Oswestry Disability
Index (ODI).27-30 The ODI is an index derived from the
Oswestry Low Back Pain Questionnaire. The self-admin-
istered questionnaire contains ten topics concerning inten-
474 European Journal of Physical and Rehabilitation Medicine August 2019
sity of pain, lifting, ability to care for oneself, ability to
walk, ability to sit, sexual function, ability to stand, social
life, sleep quality, and ability to travel. Each topic category
is followed by 6 statements describing different potential
scenarios in the patient’s life relating to the topic. Patients
are asked to indicate the statement that most closely re-
sembles their situation. Statements are associated with
scores from 0 to 5, where 0 indicates the lowest disability
and 5 the most severe disability. The sum of the ten scores
is expressed as a percentage of the maximum score (50)
and ranges from 0= no disability to 100%= maximum dis-
ability. A score from 0% to 20% indicates minimal disabil-
ity; from 21% to 40%, moderate disability; from 41% to
60%, severe disability; from 61% to 80%, crippling back
pain; from 81% to 100%, patients are either bed-bound or
exaggerate their symptoms.
Statistical analysis
Statistical analysis was blinded because the allocation
of patients treated with intradermal diclofenac or lysine
acetylsalicylate in group A and B was unknown during
statistic analysis. Data were summarized by descriptive
statistics. Comparisons within and between groups were
performed using the t-test, the χ2 test, and analysis of vari-
ance (ANOVA) models, as appropriate. A P value ≤0.05
was considered to be statistically significant both for pri-
mary and secondary outcome.
Results
We included a total of 101 patients with nonspecific
chronic low back pain in our analysis; 51 treated with di-
clofenac-based mesotherapy (group A) and 50 with lysine
acetylsalicylate-based mesotherapy (group B) (Figure 1).
Demographic characteristics of the two treatment groups
are summarized in Table I. In both groups, female patients
were in the majority (65% in group A and 60% in group
B); mean (±SD) age in both groups was similar (respec-
tively, 62.8±10.7 and 64.1±15.8 years, respectively). Re-
garding clinical characteristics, significantly more patients
in group A than in group B had ≥1 comorbidities (72.5%
vs. 57.9%, respectively, P<0.001) (Table I).
Before initiating mesotherapy (T0), patients in group A
reported severe pain (mean VAS Score±SD, 7.6±1.3 cm),
while pain in group B was of moderate intensity (mean
VAS Score, 6.7±1.6 cm). Disability was severe in group
A (mean ODI Score, 44.8±15.6) and moderate in group B
(39.0±16.7). In both groups, mesotherapy was associated
with statistically significant improvements in pain inten-
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access
COPYRIGHT 2019 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically

to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,

DICLOFENAC FOR NONSPECIFIC CHRONIC LOW BACK PAIN RONCONI

Records of patients with non specific

chronic low back pain (N.=101) Group A
Group B

T0 T0 10
7.6
6.7
Group A: N.=51 Group B: N.=50 5.4 5.3
VAS: 7.61±1.29 VAS: 6.7±1.29 8 4.4

Mean VAS score

MPQ: 22.49±9.96 MPQ: 22.49±9.96
ODI: 44.8±15.5 ODI: 44.8±15.5 6
2.8 2.7 3.4
4
T1 T0
Group A: N.=51 Group B: N.=50
2
VAS: 2.81±1.19 VAS: 5.38±2.57
MPQ: 7.35±5.06 MPQ: 14.4±11.4
ODI: 16.12±9.46 ODI: 33.44±17.9 0
T0 T1 T2 T3 T0 T1 T2 T3
T2 T2
A
Group A: N.=51 Group B: N.=50
VAS: 2.65±1.14 VAS: 5.30±2.80 50
MPQ: 7.20±5.05 MPQ: 14.6±11.4
ODI: 15.9±9.13 ODI: 34.35±18.5 Drop out
9: assumed FANS 40

Mean MPQ score

2: physiotherapy 22.5
T3 T3 5: failed T3 control 18.7
visit
30 14.4 14.7
Group A: N.=51 Group B: N.=50 11.2
VAS: 3.37±0.93 VAS: 4.37±2.90 20
MPQ: 7.98±4.65 MPQ: 11.24±10.13 7.3 7.2 8.0
ODI: 19.6±10.74 ODI: 33.06±17.06
10
Figure 1.—Study algorithm.
0
T0 T1 T2 T3 T0 T1 T2 T3
Table I.—Demographic, clinical characteristics and baseline val- B
ues of outcome measures at baseline of patients in diclofenac
(group A) or lysine acetylsalicylate (group B) mesotherapy group. 100
Group A Group B P value 80
(N.=51) (N.=50)
Mean ODI score

44.8 39.0
Age, years, mean (±SD) 62.8 (10.7) 64.1 (15.8) 0.630 60 33.4 34.3 33.1
Gender, N. (%) 0.625
Female 33 (64.7) 30 (60.0) 40 19.6
Male 18 (35.3) 20 (40.0) 16.1 16.0
20
Occupational status, N. (%) <0.001
Retired 38 (74.5) 19 (50.0)a 0
Employed 13 (25.5) 6 (15.8)
T0 T1 T2 T3 T0 T1 T2 T3
Self-employed 0 1 (2.6) C
Student 0 1 (2.6)
Housewife 0 11 (28.9) Figure 2.—Low back pain severity scores and disability scores in pa-
Educational level, N. (%) 15.9±9.13 34.35±18.52 <0.001 tients receiving mesotherapy with a drug mixture containing diclofenac
Primary school 0 9 (24.3)b (group A) or lysine acetylsalicylate (group B) at baseline (T0) and after
Secondary school 33 (64.7) 8 (21.6) treatment (A) VAS Pain Score; B) Short Form-McGill Pain Question-
High school 13 (25.5) 18 (48.6) naire (MPQ) Score; C) Oswestry Disability Index (ODI). ODI scores
are expressed as % of the total score. Differences between (ANOVA)
University degree 5 (9.8) 2 (5.4) and within (two-tailed test) groups were statistically significant. T1=
Comorbidities, N. (%) <0.001 end of 5 mesotherapy sessions; T2= 1-month follow-up; T3= 3-month
Yes 51 (100.0) 29 (76.3)a follow-up.
No 0 9 (23.7)
Cardiovascular 14 (27.5) 5 (13.2)
Respiratory 0 2 (5.3)
Patients with >1 comorbidity, 37 (72.5) 22 (57.9) <0.001 sity compared with baseline at all time points (Figure 2).
N. (%) At the end of mesotherapy treatment (T1), the mean VAS
Drop out (N.) 0 15 Score had decreased by -4.8±1.1 points in group A and by
VAS T0 7.61±1.29 6.74±1.61 0.004*
SF-MPQ T0 22,49±9.96 18.66±9.65 0.053 -1.4±1.9 points in group B. These improvements were sus-
OSW T0 44.80±15.55 39.04±16.06 0.075 tained throughout follow-up in both groups (Figure 2A).
Independent samples t-test was used for statistical analysis of age. For the A similar trend was observed for the other pain intensity
remaining variables, the χ2 test was used. Values are expressed as mean (SD).
VAS: Visual Analog Scale; ODI: Oswestry Disability Index; SF-MPQ: Short-
score (MPQ, Figure 2B) and the disability score (ODI,
Form-McGill Pain Questionnaire. Figure 2C). In Table II we described mean values and stan-
aData available for 38 patients only; bdata available for 37 patients only.
dard deviations of outcome measures at T0, T1, T2, T3 of

Vol. 55 - No. 4 European Journal of Physical and Rehabilitation Medicine 475

 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access
COPYRIGHT 2019 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically

to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,

RONCONI DICLOFENAC FOR NONSPECIFIC CHRONIC LOW BACK PAIN

Table II.—Mean values and standard deviations of outcome meas-

ures at T0, T1, T2, T3 of patients in diclofenac (group A) or lysine ODI score 0-20
acetylsalicylate (group B) mesotherapy group. ODI score 21-40
ODI score 41-60
Group A Group B 100
P value ODI score 61-80
N.=51 N.=50
VAS T0 7.61±1,29 6,74±1,61 0.004* 80
VAS T1 2.82±1.19 ** 5.38±2.57 ** <0.001*

Patients (%)
60
VAS T2 2.65±1.14 ** 5.30±2.80 ** <0.001*
VAS T3 3.37±0.93 ** 4.37±2.92 ** <0.025* 40
SF-MPQ T0 22,49±9.96 18.66±9.65 0.053
SF-MPQ T1 7.35±5.06 ** 14.40±11.40 <0.001* 20
SF-MPQ T2 7.20±5.05 ** 14.65±11.41 <0.001*
SF-MPQ T3 7.98±4.65 ** 11.24±10.13 ** <0.052 0
ODI T0 44.80±15.55 39.04±16.66 0.075 T0 T1 T2 T3
ODI T1 16.12±9.46 ** 33.44±17.92 ** <0.001*
A
ODI T2 15.9±9.13 ** 34.35±18.52 <0.001*
ODI T3 19.60±10.74 ** 33.06±17.06 ** <0.001* 100

ANOVA P value two independent samples comparison: *P level<0.05; paired 80

samples test significant results **P≤0.003 for within-group T0/T1, T0/T2, T0/
T3 in each groups.

Patients (%)
60
SD: standard deviation; VAS: Visual Analog Scale; ODI: Oswestry Disability
Index; SF-MPQ: Short-Form-McGill Pain Questionnaire.
40

20
patients in diclofenac (group A) and lysine acetylsalicylate
(group B) mesotherapy group and significant values. At 0
T1, the mean MPQ Score had decreased from baseline by B T0 T1 T2 T3

-15.1±8.6 in group A and by -4.3±11.9 in group B; the dis-
ability score had improved by -28.7±14.1 and -5.6±12.3,
respectively.
Improvements in pain intensity and disability in group
A were consistently more substantial than those reported
in group B (Figure 2); such differences between groups
were statistically significant across all variables measured
and throughout the observation period (with only excep-
tion MPQ at T3. Improvements with diclofenac-based me-
sotherapy were greater than those with lysine acetylsalicy-
late-based mesotherapy by -1.4 points on the VAS Scale,
-5.8 points of the MPQ Score, and -17.1 points of the ODI
Score (Table III).
At baseline, 70% of patients in group A had severe-crip-
pling disability due to low back pain (ODI >40%). At T1
and during follow-up the proportion of patients with se-
vere-crippling disability decreased to 5.9% (Figure 3). In
patients of group B, treatment with mesotherapy was also
associated with a decrease in the proportion of patients
with severe-crippling disability, from 50% at baseline to
Figure 3.—Proportions of patients with minimal, moderate, severe, or
crippling disability before (T0) and after treatment with (A) diclofenac-
based and (B) lysine acetylsalicylate-based mesotherapy. Differences
between treatment groups were statistically significant at T1 (end of the
5-week treatment), T2 (1 month post-treatment) and T3 (3 months post-
treatment).
34% at T1. Differences between groups were statistically
significant at T1, T2, and T3.
Both treatments were well tolerated. There was no re-
port of adverse events associated with the intervention and
during the 3 months of follow-up.
Discussion
This retrospective analysis found that intradermal admin-
istration of analgesic solutions via mesotherapy was as-
sociated with significant pain and disability improvements
in patients with nonspecific chronic moderate-to-severe
low back pain. The reductions in pain severity and dis-
ability scores were observed already after 5 sessions of

Table III.—Mean differences between group A (diclofenac) and group B (lysine acetylsalicylate) in the changes of pain intensity and dis-
ability scores from baseline (T0) to end of study (T3).
VAS SF-MPQ ODI
Change from T0 to T3 -1.37 (-2.47 to -0.26) -5.81 (-10.65 to -0.98) -17.05 (-24.03 to -10.06)
Between-group differences are shown as mean values (95% confidence interval). Differences between groups were statistically significant across the three variables.
VAS: Visual Analog Scale; ODI: Oswestry Disability Index; SF-MPQ: Short-Form-McGill Pain Questionnaire.

476 European Journal of Physical and Rehabilitation Medicine August 2019

 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access
COPYRIGHT 2019 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
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DICLOFENAC FOR NONSPECIFIC CHRONIC LOW BACK PAIN RONCONI
mesotherapy (2½ weeks) and were maintained for up to 3
months of follow-up. Diclofenac-based mesotherapy was
associated with significantly greater improvements in pain
severity and functional disability than lysine acetylsalicy-
late-based mesotherapy. Following mesotherapy with di-
clofenac, most patients (>60%) reported mild disability,
while among those treated with lysine acetylsalicylate-
based mesotherapy, fewer than 40% reported mild disabil-
ity during follow-up. Both treatments were well tolerated,
and the benefits were sustained over 3 months.
The experience of pain is recognized as being subjec-
tive and multidimensional. Therefore, self-report of pain
intensity is considered of prime importance in the assess-
ment of pain.31, 32 The improvements in pain intensity and
disability achieved with diclofenac-based mesotherapy in
this study represent a clinically relevant difference that is
perceived by patients as adequate analgesic control, ac-
cording to accepted outcome measures.32
The efficacy of diclofenac mesotherapy in relieving
pain in this study is consistent with the results of studies
investigating mesotherapy in other conditions.15, 17, 18
Authors analyzed diclofenac mesotherapy, 117 patients
with anserine bursitis associated with knee osteoarthritis
were randomized to nine sessions of mesotherapy with so-
dium diclofenac 25 mg/mL over 3 weeks or to once-daily
oral diclofenac 50 mg for 3 weeks.18 Pain level decreased
significantly after treatment in both groups; mean pain se-
verity VAS Score was reduced from 7.0 at baseline to 2.0
at week 3 in the diclofenac mesotherapy group, compared
with 7.5 to 3.0 in patients receiving systemic treatment.
Disability scores significantly improved from baseline in
both groups. However, a reduction of the hypoechoic re-
gion related to anserine bursitis measured by ultrasonogra-
phy was observed only in the diclofenac group.18 It should
be noted that the administration of diclofenac via meso-
therapy provided the same therapeutic benefit in terms of
reduction in pain intensity and disability in daily life activ-
ity as conventional oral NSAID therapy, despite the mark-
edly lower amount of diclofenac administered to patients
in the mesotherapy group. This is consistent with other
studies that have compared mesotherapy with convention-
al oral NSAID therapy.12, 33, 34 The comparable efficacy of
mesotherapy and conventional systemic administration,
despite the disparities in drug dosage, may be explained in
part by the comparatively slow absorption of drugs when
administered by the subcutaneous route, leading to a high
drug concentration localized in the area being treated.12, 18
However, it has also been hypothesized that local analge-
sic and mechanical effects caused by needle insertion and
Vol. 55 - No. 4 European Journal of Physical and Rehabilitation Medicine 477
liquid injection into cutaneous tissues may contribute to
the efficacy of mesotherapy.16
Our study confirms that the diclofenac/β-cyclodextrin
injectable formulation is suitable for use in mesotherapy.
Our center has developed a successful protocol in which
the product is diluted in physiological saline, yielding a
solution that can be injected intradermally without com-
plications, despite having a cloudy appearance. It has
recently been reported that alkalinization of solutions of
diclofenac/β-cyclodextrin and local anesthetics with bi-
carbonate ensures optimal solubility of the mixture com-
ponents, producing a clear solution suitable for mesother-
apy.35 However, our routine clinical experience suggests
that a cloudy solution can be used effectively, provided no
bulky precipitates are apparent on visual inspection.
Limitations of the study
This study had a number of limitations. First the retrospec-
tive study design, did not allow us to make extrapolation
regarding results. An important source of bias could be
that operators were not blinded about drugs. Another limi-
tation is the short observation time, probably not sufficient
to describe long-term effects of treatment in persistent low
back pain.
The group receiving the diclofenac-based treatment had
significantly higher baseline pain and disability scores but
showed better results compared with other group; it should
be noted, however, that for all three measures, the differ-
ences were smaller between groups than the cutoff consid-
ered clinically meaningful.
Furthermore, although all patients in the diclofenac
group (group A) were evaluable at all time points, 15 pa-
tients in group B were not available for analysis of out-
comes at T3 (3-month follow-up). This may have been due
to a number of reasons, including having taken systemic
analgesics or undergone physiotherapy treatment for their
condition or failing to attend the scheduled clinic visit.
A possible placebo effect could also be present in this
study in both groups: both groups showed a significant im-
provement, which could imply that it was because of the
invasive treatment modality, and not the specific agent.
Despite these limitations, this study provides real-world
evidence about the effectiveness of mesotherapy with
two different drug mixtures in relieving low back pain
and disability, assessed using three validated scoring sys-
tems. Based on these findings, mesotherapy appears to be
a valid strategy for effectively improving low back pain
while limiting the systemic exposure to NSAIDs, as rec-
ommended by current guidelines.
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access
COPYRIGHT 2019 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
RONCONI DICLOFENAC FOR NONSPECIFIC CHRONIC LOW BACK PAIN
Conclusions
It is possible that diclofenac mesotherapy is a viable treat-
ment option for nonspecific chronic moderate-to-severe
low back pain. The highly soluble diclofenac-cyclodextrin
complex is suitable for administration by the minimally-
invasive mesotherapeutic technique. These promising
findings need to be confirmed in prospective randomized
controlled trials.
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COPYRIGHT 2019 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically

to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,

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Conflicts of interest.—The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
Funding.— The statistical analysis was funded by IBSA Farmaceutici Italia Srl.
Acknowledgements.—Editorial assistance during manuscript preparation was provided by Lorenza Lanini and Ray Hill, independent medical writers, on
behalf of Springer Healthcare Communications. The authors also thanks Giorgio Reggiardo, Mediservice, Italy, who performed the statistical analysis.
Article first published online: February 15, 2019. - Manuscript accepted: February 14, 2019. - Manuscript revised: January 10, 2019. - Manuscript received:
July 9, 2018.

Vol. 55 - No. 4 European Journal of Physical and Rehabilitation Medicine 479