Effectiveness and safety of
arnica Montana in Post-Surgical
Setting, Pain and Inflammation
Tommaso Iannitti, PhD,
1
*JulioC
esar Morales-Medina, PhD,
2
Paolo Bellavite, MD,
3
Valentina Rottigni, MSC,
4
and Beniamino Palmieri, MD, PhD
4
Arnica montana has been widely used as a homeopathic remedy for the treatment of several inflam-
matory conditions in pain management and postoperative settings. This review gives an overview of
the therapeutic use of Arnica montana in the above-mentioned fields also focusing on its mechanisms
of action learned from animal models and in vitro studies. Arnica montana is more effective than
placebo when used for the treatment of several conditions including post-traumatic and postoper-
ative pain, edema, and ecchymosis. However, its dosages and preparations used have produced
substantial differences in the clinical outcome. Cumulative evidence suggests that Arnica montana
may represent a valid alternative to non-steroidal anti-inflammatory drugs, at least when treating
some specific conditions.
Keywords: Arnica montana, homeopathy, herbal medicine, side effect profile, inflammation, pain,
surgery, trauma, ecchymosis, edema
INTRODUCTION
The use of complementary therapies, including plant
remedies, is widespread and rapidly expanding on
a worldwide scale. Plant remedies are traditionally
used in a variety of pharmacopoeias and on a large
scale of doses, including extremely low-dose homeo-
pathic formulations. Herbal medicine or botanical
medicine or phytomedicine refers to the therapeutic
use of herbs, herbal materials, herbal preparations,
and finished herbal products containing plant
materials (seeds, berries, roots, leaves, bark, or flow-
ers) or parts as active ingredients. Homeopathy is
based on the concept “similia similibus curentur”
1
according to which symptoms, caused by the origi-
nal substance in healthy subjects, can be reversed by
the homeopathic remedy in patients having similar
symptoms. Therefore, homeopathic drug adminis-
tration is based on 3 principles: (1) the administra-
tion of an active element to healthy volunteers
brings manifestation of a series of clinical symptoms
at physical and psychological levels; (2) low doses of
thesameelement(s)reversepathological states in ill
organisms presenting a similar symptomatologic
pattern; (3) the homeopathic treatment retains its
biological activity because of a peculiar method of
dilution followed by vigorous shaking, that is, “suc-
cussion”, even if, after several successive serial dilu-
tions, the probability of the presence of any active
molecule is very low.
2,3
There are several models
attempting to explicate how the peculiar homeo-
pathic procedure of succussion can change solvent
structure at nanoscopic level and justify the perma-
nence of pharmacological properties throughout di-
lutions.
4–7
1
School of Biomedical Sciences, University of Leeds, Leeds, United
Kingdom;
2
Douglas Mental Health Research Institute, McGill
University, Montreal, Quebec, Canada;
3
Department of Pathology
and Diagnostics, University of Verona, Verona, Italy; and
4
Department of Surgery and Surgical Specialties, University of
Modena and Reggio Emilia Medical School, Surgical Clinic,
Modena, Italy.
The authors contributed equally to this work.
The authors have no conflicts of interest to declare.
*Address for correspondence: School of Biomedical Sciences, Uni-
versity of Leeds, Mount Preston St, Garstang building, Leeds, LS2
9JT, United Kingdom. E-mail: tommaso.iannitti@gmail.com
American Journal of Therapeutics 23, e184–e197 (2016)
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5
Arnica is one of the most popular medications in
complementary medicine. This remedy can be ex-
tracted from several plant species belonging to the
Aesteraceae family including Arnica montana,Arnica
chamissonis,Arnica fulgens,Arnica cordifolia and Arnica
sororia, and it is widely sold as tincture, ointment,
cream, gel, and tablet. In 2009, a study showed that
Asteracea-containing remedies were frequently used
in German primary care, and their uses were not asso-
ciated with serious adverse reactions.
8
Arnica can be
used as a homeopathic or herbal remedy. There are
also Arnica-based complex formulations which can
include up to 32 different plant species which share
morphological characteristics and therapeutic proper-
ties to treat inflammation, wounds, hematoma, and
contusion.
9
Among the different varieties, Arnica mon-
tana L. is one of the most used varieties and receives
different local names including leopard’s bane, wolf’s
bane, mountain tobacco, and mountain snuff.
10
This
herb (here referred as Arnica), native of the Siberian
mountains and Central Europe, has been used for the
treatment of numerous pathological conditions,
including pain, stiffness, and swelling associated with
trauma, contusions, sprains, myocarditis, cardiac
insufficiency, arteriosclerosis, angina pectoris, postop-
erative clinical conditions, and for symptomatic relief
in osteoarthritis.
10–12
In traditional medicine, patients
suffering from traumatic disease often use Arnica as an
“alternative”treatment, in the hope of resolving pain
and reducing the use of conventional drugs which
may cause adverse effects. Furthermore, according to
a review concerning the use of alternative and comple-
mentary medicine for rheumatological conditions such
as osteoarthritis, rheumatoid arthritis, and fibromyal-
gia, Arnica was used in 18% of patients attending the
rheumatology department in a Mexican hospital.
13
In
vitro studies have shown that the most active compo-
nents of Arnica, as well as of other members of the
Asteraceae family, are helenalin and other sesquiter-
pene lactones such as 11a,13-dihydrohelenalin and
chamissonolid. Early on, Lyss et al
14
showed that hel-
enalin inhibits the transcriptional factor nuclear factor
kappa B (NF-kB) through the alteration and stabiliza-
tion of the NF-kB/inhibitor of kappa B (IkappaB) com-
plex in T cells, B cells, and epithelial cells and
abrogates kappa B-driven gene expression. This repre-
sents one of the earliest evidences of the anti-
inflammatory properties of Arnica. Later work showed
that helenalin can inhibit human neutrophil migration
and chemotaxis
15
and activities of 5-lipoxygenase and
leukotriene C4 synthase.
16
Helenalin dose-
dependently reduced cell-proliferation in cluster of dif-
ferentiation (CD)4
+
T cells after the activation of the
mitochondrial apoptosis pathway and p53 rapid
stabilization and nuclear localization.
17
Furthermore,
it arrested activated CD4
+
T cell cycle in the G2/M
phase through an increase in p27
KIP1
, p21
WAF1/CIP1
,
and cyclin D2, and a decrease in cyclin B1 and cyclin
A.
17
Helenalin also decreased the expression of cell-
surface receptors CD25, CD28, CD27, and CD120b
which play a key role in NF-kB activation in T cells,
17
supporting the mechanism proposed by Lyss et al in
1997.
14
NF-kB controls the transcription of various
cytokine and adhesion molecule genes in addition to
genes required for antigen presentation.
18
NF-kB acti-
vation is associated with the induction of pain and
inflammation, as observed in animal models of inflam-
matory pain (rat carrageenan pleurisy and mouse car-
rageenan air pouch), characterized by the release of
proinflammatory cytokines (tumor necrosis factor-alpha
[TNF-a] and interleukin-1beta [IL-1b]) and local recruit-
ment of leukocytes.
19
The ability of Arnica to inhibit
activation of transcription factors NF-kBandnuclear
factor of activated T cells and proinflammatory cyto-
kines IL-1band TNF-acorrelate with their quantitative
and qualitative content of sesquiterpene lactones.
20
Additionally, Arnica treatment showed a 4.5-fold inhi-
bition of nitric oxide production, a reduction in the
levels of inducible nitric oxide synthase and
cyclooxygenase-2 protein, a 3-fold reduction in TNF-a
level, and prevented nuclear translocation of NF-kBin
J774 murine macrophage cells challenged with lipopoly-
saccharide.
21
Furthermore, in the rat, 21-day oral treat-
ment with Arnica 30
th
centesimal dilution (30c)
protected against hepatic mitochondrial membrane
FIGURE 1. Mechanisms underlying Arnica effectiveness.
COX-2, cyclooxygenase-2; TNF-a, tumor necrosis factor
alpha; IL-1b, interleukin-1 beta; NO, nitric oxide; iNOS,
inducible nitric oxide synthase; NF-kB, nuclear factor
kappa B; IkB, inhibitor of kappa B.
Effectiveness and Safety of Arnica montana e185
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5
permeabilization induced by Ca
2+
and/or Fe
2+
-citrate–
mediated lipid peroxidation and fragmentation of pro-
teins due to attacks by reactive oxygen species.
22
In
Figure 1, we have summarized the mechanisms under-
lying Arnica effectiveness. As an herbal formulation,
Arnica is generally used only topically (on the skin)
because of side effects which can be observed after oral
administration. Oral homeopathic remedies do contain
Arnica, but they use an extremely diluted form which is
not considered dangerous. The literature concerning
Arnica in both phytotherapeutic and homeopathic for-
mulations is rapidly increasing, together with the
knowledge of its active principles and putative mecha-
nisms of action. In this review, we grouped clinical evi-
dence into 2 sections. The first group comprises the use
of Arnica as topical formulation, either as a phytother-
apic extract (higher dosage not succussed) or homeo-
therapic (diluted and succussed preparations), whereas
the second group comprises the use of homeopathic
preparations administered by oral or topical route.
The focus was on preclinical and clinical use of Arnica
for the treatment of inflammatory conditions, in pain
management and postoperative settings.
REVIEW CRITERIA
This review gives an overview of the literature in the
aforementioned fields, from 1997 to 2013. The princi-
pal information sources are drawn from current read-
ing of major complementary and alternative medicine
journals, screening of the Hom-Inform Bibliographic
Database and Information Service Databases (British
Homeopathic Library, http://hominform.soutron.
com/), literature search using MEDLINE, the
Cochrane Database of Systematic Reviews, and cross-
referencing among published articles. Our analysis
includes controlled clinical trials (with and without
randomization), observational studies, and case series,
but it excludes single case reports. We also consulted
previously published systematic reviews and meta-
analyses which have covered the subject up to now.
Finally, some relevant studies concerning the mecha-
nism(s) of action and laboratory studies are reported.
PRECLINICAL STUDIES
Arnica hasbeenusedasasingleremedy
23–25
in preclinical
models of acute (carrageenan- and homologous blood–
induced rat paw edema) and chronic (nystatin-induced
rat paw edema) inflammation and histamine-induced
increased vascular permeability.
23–26
For instance, autol-
ogous blood-induced edema was reduced 1, 3, and 5
hours after subplantar but not after oral administration
of Arnica 4th decimal dilution (4D), when compared with
control animals.
23
Lussignoli et al
26
replicated this finding
and showed that administration of Arnica alone or as
a homeopathic formulation (Traumeel) an hour before
or after the injection of autologous blood, decreased
pawedemaandenhancedthehealingprocess.Reduction
in paw edema coupled with a decrease in systemic
interleukin-6 (IL-6) at 5 hours after blood edema induc-
tion.
26
Subchronic oral administration of Arnica 6c also
reduced carrageenan-induced rat paw edema by 30%.
25
The reduction in paw edema was evident starting from
1 hour post-carrageenan, and lasted at least 6 hours. In
the same study, oral treatment with Arnica 6c before 8.5%
nystatin-induced inflammation showed a reduction in the
edema at 6 hours compared with the control group.
However, no effect was observed when adminis-
tered after nystatin. Furthermore, Arnica 6c blocked
histamine-induced increase in vascular permeability
when administered 3 days before stimulus. Oral Arnica
6c administered every 15 minutes between 30 and 180
minutes, after 1% kappa carrageenan inoculation, was
effective in reducing late but not early edema in the rat
when compared with control groups.
24
Edema ameliora-
tion coupled with a decrease in the mast cell degranula-
tion and an increase in the lymphatic vessel diameter.
Helenalin, a sesquiterpene lactone and one of the
main active constituent of Arnica extract,
14
inhibited
carrageenan-induced paw edema and complete Freund’s
adjuvant-induced arthritis in the rat.
27
Topical application
of Arnica 3D gel (10%), combined with microcurrent
(10 mA for 2 minutes) application, significantly improved
wound healing in the linear incision wound model in the
rat back.
28
The evidence was consistent with a signifi-
cantly larger total number of cells and higher percentage
of mature collagen fibers in the wound, as assessed by
structural and morphometric analysis. Therefore, these
results strongly support the relevance of Arnica in the
treatment of inflammatory-related processes.
CLINICAL STUDIES
Topical applications of phytotherapeutic
preparations
Up to now, several clinical trials involving the use of
topical Arnica have been performed aiming to reduce
laser-induced bruising and osteoarthritis-related symp-
toms. We have summarized these studies in Table 1.
Laser-induced bruising
Daily application of 2 extracts based on a combination
of Arnica and stinging nettle (Combudoron liquid and
Combudoron gel; 0.5 mL per lesion for 30 minutes for
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5
Table 1. Clinical efficacy of Arnica montana.
Author(s),
year Design No. Patients Pathology Treatment Outcome Homeopathy
Herbal
medicine
Kaziro,
1984
29
Randomized
double-blind
placebo-
controlled
trial
118 Post-surgical
complications
after removal
of impacted
wisdom teeth
Arnica 200c versus
metronidazole
versus placebo
Metronidazole was more
effective in pain control
(P,0.001 and P,0.01),
swelling prevention
(P,0.01 and P,0.05)
and healing promotion
(P,0.01 and P,0.01)
when compared with
Arnica and placebo,
respectively
Yes
Albertini
and
Goldberg,
1986
30
Randomized
placebo-
controlled
trial
30 Dental neuralgic
pain after
tooth
extraction
Arnica 7c and
Hypericum 15c
versus placebo
76% of the
patients treated with
homeopathic remedies
had pain relief versus
40% of patients
receiving placebo
Yes
Zell et al,
1988
31
Randomized
double-blind
placebo-
controlled
study
69 Acute sprains of
the ankle joint
Traumeel
ointment versus
placebo
24 patients were pain-free
on treatment day 10,
whereas on the same
day, only 13 patients
treated with placebo had
no pain
Yes
Dorfman
et al,
1988
32
Double-blind,
placebo-
controlled
clinical study
39 Prolonged
venous
perfusion
Arnica 5c Arnica reduced pain,
hyperemia, edema, and
hematoma formation.
Improvement in the blood
flow and slight increase in
coagulation factors and in
platelet aggregation were
observed after Arnica
treatment
Yes
Baillargeon
et al,
1993
33
Randomized
double-blind,
2-period,
crossover,
clinical trial
18 Blood
coagulation
Arnica 5c versus
placebo
An increase in bleeding time
and a decrease in
fibrinogen were observed
30 minutes after Arnica
administration
Yes
Lokken et al,
1995
34
Randomized
double-blind,
placebo-
controlled
crossover
trial
24 Pain after
surgical
removal of
bilaterally
impacted
mandibular
third molars
Arnica 30D versus
placebo
No difference in
postsurgical pain was
observed between Arnica
and placebo.
Postoperative swelling
and bleeding were not
significantly affected by
homoeopathy
Yes
Hart et al,
1997
35
Randomized
double-blind
controlled
study
73 Pain and
postoperative
recovery after
total
abdominal
hysterectomy
Arnica 30c versus
placebo
No significant difference
was observed between
Arnica and placebo
Yes
Vickers et al,
1998
36
Randomized,
double-blind
placebo-
controlled
trial
400 Muscle soreness
after long-
distance
running
Arnica 30D versus
placebo
No significant change in
muscle soreness after
long-distance running
was observed when
comparing Arnica to
placebo
Yes
(Continued on next page)
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Table 1. (Continued) Clinical efficacy of Arnica montana.
Author(s),
year Design No. Patients Pathology Treatment Outcome Homeopathy
Herbal
medicine
Ramelet
et al,
2000
37
Randomized,
prospective,
multicenter
double-blind
trial
130 Saphenous
stripping
Arnica 5c versus
placebo
No significant difference in
postoperative
hematomas was
observed between
Arnica and placebo
Yes
Alonso et al,
2002
11
Randomized,
double-blind
placebo-
controlled
trial
19 Laser-induced
bruising
Arnica gel versus
vehicle
No difference was
observed between
Arnica and vehicle
administered prior or
after injury
Yes
Jeffrey and
Belcher,
2002
38
Randomized
double-blind,
placebo-
controlled
study
37 Hand surgery
(endoscopic
carpal tunnel
release)
Arnica 6D tablets
and Arnica
ointment versus
placebo
No difference in grip
strength or wrist
circumference was
found between Arnica
and placebo. A
significant reduction in
pain was observed in
the Arnica-treated group
versus placebo.
(P50.03)
Yes
Knuesel
et al,
2002
39
Open
multicenter
trial
79 Mild–moderate
knee
osteoarthritis
Arnica gel Median total scores on the
Western Ontario and
McMaster Osteoarthritis
Index were significantly
decreased in the
intention-to-treat and per-
protocol populations
(both P,0.0001). Scores
on the pain, stiffness, and
function subscales were
also signifcantly
decreased
Yes
Wolf et al,
2003
39
Prospective,
randomized,
double-blind,
placebo-
controlled
pilot trial
60 Varicose vein
surgery
Arnica 12D versus
placebo
Hematoma surface was
reduced with Arnica
by 75.5% and with
placebo by 71.5%
(not significant). Pain
score decreased by
162.2 points with
Arnica and 0.3 60.8
points with placebo not
significant
Yes
The results of the study
showed a trend
towards a beneficial
effect of Arnica
regarding the
reduction in hematoma
and pain during the
postoperative course
Stevinson
et al,
2003
3
Randomized
double-blind
placebo-
controlled
trial
62 Surgery for
carpal tunnel
syndrome
Arnica 6c or 30c
versus placebo
No significant change in
pain and bruising were
observed after
administration of Arnica
or placebo
Yes
(Continued on next page)
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5
Table 1. (Continued) Clinical efficacy of Arnica montana.
Author(s),
year Design No. Patients Pathology Treatment Outcome Homeopathy
Herbal
medicine
Tveiten and
Bruset,
2003
41
Randomized
double-blind
placebo-
controlled
study
82 Muscle soreness
and cell
damage after
marathon
running
Arnica versus
placebo
Muscle soreness
immediately after the
marathon was lower in
the Arnica group versus
placebo (P50.04)
Yes
Brinkhaus
et al,
2006
42
Three
randomized,
placebo-
controlled,
double-blind,
sequential
clinical trials
227 Postoperative
swelling and
pain after
arthroscopy,
artificial knee
joint
implantation,
and CLR
Arnica 30D versus
placebo
Arnica was effective on
swelling and pain only
in the CLR trial
(P50.019)
Yes
Seeley et al,
2006
43
Prospective
randomized
double-blind
placebo-
controlled
study
29 Rhytidectomy Arnica (SinEcch)
versus placebo
Patients receiving Arnica
had a smaller area of
ecchymosis on
postoperative days 1, 5,
7, and 10. These
differences were
statistically significant
only on postoperative
days 1 (P,0.005) and 7
(P,0.001)
Yes
Schneider
et al,
2007
44
Multicenter,
prospective,
comparative
observational
cohort study
133 Muscoskeletal
trauma and
injuries
Traumeel versus
conventional
medicines
Complete resolution
of pain and inflammatory
symptoms at the end of
therapy were observed in
59.4% of patients in the
Traumeel group and in
57.8% of patients in the
conventional medicine
group
Yes
Robertson
et al,
2007
52
Randomized
double-blind,
placebo-
controlled
trial
111 Tonsillectomy Arnica 30c versus
placebo
Arnica reduced pain scores
(P,0.05). No difference
was observed in
analgesia consumption,
complications, and
return to normal
activities when
comparing Arnica to
placebo
Yes
Totonchi
and
Guyuron,
2007
51
Randomized
double-blind
clinical study
48 Rhinoplasty Arnica (SinEcch)
versus
intravenous
dexamethasone
plus oral
tapering dose of
methyl-
prednisone or
no treatment
(control group)
Arnica and
dexamethasone reduced
swelling-edema if
compared with control
(P,0.0001). Arnica and
control group exhibited
more resolution of
ecchymosis if compared
with dexamethasone
(P,0.05)
Yes
Widrig et al,
2007
12
Randomized,
double-blind
study
204 Hand
osteoarthritis
Arnica gel versus
ibuprofen gel
Arnica and ibuprofen
were equally effective
for the treatment of
hand osteoarthritis as
Yes
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5
Table 1. (Continued) Clinical efficacy of Arnica montana.
Author(s),
year Design No. Patients Pathology Treatment Outcome Homeopathy
Herbal
medicine
far as pain reduction,
hand function, number
of painful joints in both
hands and intensity of
morning stiffness in the
worst affected hand
were concerned
Paris et al,
2008
2
A phase 3
monocentric
randomized
placebo-
controlled
study
158 Knee ligament
reconstruction
Granule
composition
containing
Arnica 5c,
Bryonia alba 5c,
Hypericum
perforatum 5c,
and Ruta
graveolens 3D
versus placebo
or no treatment
Homeopathic treatment
was not superior to
placeboinreducing24h
morphine consumption
after knee ligament
reconstruction. No
significant difference in
pain assessed by visual
analog scale was
observed between
Arnica and placebo
Yes
Karow et al,
2008
53
Randomized
double-blind,
parallel-
group study
88 Hallux valgus
surgery
Arnica 4D versus
diclofenac
sodium
Arnica and diclofenac had
equivalent efficacy on
wound irritation,
patient mobility, and
use of analgesics.
Diclofenac was more
effective in reducing
pain if compared with
Arnica (P50.027)
Yes
Adkison
et al,
2010
46
Randomized,
double-blind,
placebo-
controlled
trial
53 Leg pain after
calf raises
Arnica cream
versus placebo
Arnica increased pain
scores if compared with
placebo (P,0.005). No
difference in muscle
tenderness and ankle
motion was observed
Yes
Cornu et al,
2010
47
Double-blind
placebo-
controlled
parallel trial
90 Aortic valve
surgery
A combination of
Arnica montana
5c and Bryonia
alba 5c granules
versus placebo
No difference between
homeopathic treatment
and placebo on
bleeding, C-reactive
protein, troponin I, and
cumulated morphine
was observed
Yes
Leu et al,
2010
48
Randomized,
double-blind
placebo-
controlled
trial
16 595-nm pulsed-
dye laser-
induced
bruises on the
bilateral upper
inner arms
5% vitamin K
versus 1%
vitamin K and
0.3% retinol or
5% vitamin K or
20% Arnica or
white petrolatum
(placebo)
The mean improvement in
bruising associated
with 20% Arnica was
greater than with white
petrolatum (P50.003),
and the mixture of 1%
vitamin K and 0.3%
retinol (P50.01) while
improvement with
Arnica was not greater
than with 5% vitamin K
cream
Yes
Huber et al,
2011
49
Single-blind,
randomized
trial
2 Erbium YAG-
laser-induced
grade-2 burns
Combudoron gel
versus
Combudoron
liquid or placebo
Eschars treated with
Combudoron fell off
earlier if compared with
placebo.
Yes
(Continued on next page)
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5
7 days) was tested on erbium YAG laser–induced
grade 2 burns. This single-blind randomized study
involved 2 healthy male subjects receiving treatment
or placebo on their backs at 4 sites. After 1 week of
treatment, the diameters of the lesions were only
slightly different between treatments. Most notably,
the eschars treated with Combudoron fell off earlier
than the placebo suggesting that Combudoron has
apositiveeffectonburnhealing.
49
In a randomized,
double-blind 2-week study, twice a day topical appli-
cation of Arnica 13gel on one side of the face, before or
after laser treatment was compared with vehicle appli-
cation on the other hemiface in 19 patients affected by
facial telangiectasias without improvement in visual ana-
log scale (VAS) bruising.
11
Contrasting results were ob-
tained in a 2-week double-blind randomized study
including 16 healthy patients who underwent creation
of 7-mm standard bruises on the upper inner arms by
a 595-nm pulsed-dye laser.
48
Comparison of VAS-
bruising scores indicated that 20% Arnica gel reduced
bruising when compared with placebo and gel contain-
ing 1% vitamin K and 0.3% retinol, whereas comparison
with 5% vitamin K gel did not show any significant
difference.
Osteoarthritis
In a randomized, double-blind 3-week study which
involved 204 patients affected by osteoarthritis of
interphalangeal joints of the hands, topical application
of a 4-cm gel strip of Arnica (50 g tincture/100 g) 3
times a day showed similar efficacy to ibuprofen
(5%) gel in reducing pain, functional capacity of the
hand, number of painful joints in both hands and
intensity of morning stiffness in the worst affected
hand.
Orally administered homeopathic formulations
Homeopathic formulations of Arnica have been
largely used in the clinical setting for the manage-
ment of knee surgery, carpal tunnel syndrome,
symptoms associated with wisdom teeth removal,
rhytidectomy, rhinoplasty, abdominal hysterectomy,
tonsillectomy, hallux valgus surgery, venous sur-
gery, hemarthrosis, aortic valve surgery, prolonged
venous perfusion, muscular pain, dental neuralgia,
and ankle sprains.
Knee surgery
Brinkhaus et al
42
tested the efficacy of oral adminis-
tration of Arnica 30D administered as supplement to
ordinary treatment (1 35 globules 2 hours before
surgery plus 3 35 globules at 3-hour intervals post-
operatively the day of surgery plus 3 35 globules
until the last follow-up) on postoperative swelling
and pain in patients undergoing different types of
knee surgery in 3 consecutive randomized placebo-
controlled clinical studies. Arnica reduced swelling
and pain after cruciate ligament reconstruction (57
patients; last follow-up at day 8), but not after
arthroscopy (227 patients; last follow-up at day 2),
artificial knee joint implantation (35 patients; last
follow-up at day 11), and cruciate ligament recon-
struction (57 patients; last follow-up at day 8).
Homeopathic treatment containing Arnica 5c, Bryo-
nia Alba 5c, Hypericum perforatum 5c, and Ruta grave-
olens 3D (4-day treatment starting 1 day before the
surgery; 5 granules per day) was not superior to
placebo in reducing 24-hour morphine consumption
after knee ligament reconstruction in a randomized
controlled study including 158 patients.
2
Table 1. (Continued) Clinical efficacy of Arnica montana.
Author(s),
year Design No. Patients Pathology Treatment Outcome Homeopathy
Herbal
medicine
gel or placebo
liquid
Kucera et al,
2011
50
Randomized
double-blind
placebo-
controlled
study
570 Acute ankle joint
distortion
Combination of
Arnica tincture
and HES (spray)
versus Arnica or
HES or placebo
On day 3–4, improvement in
pain on active motion was
significantly higher in the
Arnica + HES group if
compared with the other 3
groups (t-test with
unadjusted baseline
values, P,4310
27
and ANCOVA after
adjustment, P,5310
–11
)
Yes
CLR, cruciate ligament reconstruction; HES, hydroxyethyl salicylate.
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Carpal tunnel syndrome
In a double-blind randomized trial involving 62 pa-
tients, Arnica 30c or 6c administered daily from 7
days before to 14 days after surgery (3 tablets) was
not effective in reducing bruising, swelling, and pain
in patients undergoing elective surgery for carpal
tunnel syndrome.
3
Wisdom teeth removal
In a double-blind trial, Arnica 200c administered to 39
patients undergoing the removal of impacted wisdom
teeth, was less effective for pain and swelling manage-
ment compared with placebo or metronidazole.
29
Arnica was also less effective in promoting healing
when compared with metronidazole.
29
In a random-
ized double-blind placebo-controlled crossover trial
including 24 patients undergoing prophylactic surgical
removal of identical bilaterally impacted mandibular
third molars, homeopathic treatment (30D) containing
Arnica,Hypericum,Staphysagria,Sedum,Phosphorus,
and Plantago did not produce any improvement in
VAS pain score, postoperative bleeding and swelling
and side effect profile when compared with the control
Table 2. Studies on Arnica montana side effect profile.
Author(s), year Formulation Pathology Side effect profile Dose
Knuesel et al,
2002
39
Gel (topical
application)
Knee osteoarthritis One allergic reaction
(not specified)
NS
Stevinson et al,
2003
3
Tablets (oral
treatment)
Hand surgery (carpal
tunnel syndrome)
Dry mouth Arnica 6c (for drowsiness
and sore tongue)
Headache Arnica 30c (for dry mouth,
headache, and feeling
“throbby”)
Feeling “throbby” in
head/neck
Drowsiness
Sore tongue
Widrig et al,
2007
12
Gel (topical
application)
Hand osteoarthritis Skin irritations
Itching
Reddening
Allergic eczema
Increased finger pain
Bronchitis
Chill
Cystitis
Rhinitis
Vertigo
NS
Karow et al,
2008
53
Pills (oral
treatment)
Hallux valgus surgery Abdominal complaints Arnica 4D
Racing heart
Cornu et al,
2010
47
Granules (oral
treatment)
Aortic valve surgery Cardiovascular events
(observed in both
homeopathy and
placebo groups)
Arnica 5c and Bryonia
alba 5c
Kucera et al,
2011
50
Spray (topical
application)
Ankle distortion Burning, reddening,
itching and urticaria
were observed in the
group receiving Arnica
and hydroxyethyl
salicylate. No adverse
reactions were observed
in patients receiving
Arnica alone.
Arnica tincture: 41.5 mg
Hydroxyethyl salicylate:
12.5 mg
NS, not specified in the article.
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5
group.
34
Furthermore, a 33% less reduction in the abil-
ity to open the mouth was observed on day 3 after
homeopathic treatment with Arnica. Ernst
45
criticized
this study, arguing that the doses were fixed and the
treatment schedule was not as flexible as homeopathy
requires.
Rhytidectomy
Arnica (SinEcch, Alpine Pharmaceuticals, San
Raphael, California; 1 dose every 8 hours for 4 days
starting from the day of surgery) was used in patients
undergoing rhytidectomy to evaluate its efficacy on
bruising caused by facelift in a prospective random-
ized double-blind study including 29 patients.
43
A
reduction in ecchymosis was observed at postopera-
tive days 1 and 7 compared with placebo, as assessed
by computer-measured skin color changes.
Rhinoplasty
In a randomized double-blind clinical study involv-
ing 48 primary rhinoplasty patients, oral Arnica
(SinEcch) administered 3 times a day for 4 days
and 10 mg intravenous dexamethasone administered
intraoperatively and followed by a 6-day oral taper-
ing dose of methyl-prednisone significantly reduced
edema rating, but not intensity and extent of ecchy-
mosis at day 2 post-rhinoplasty when compared with
the control group. At postoperative day 8, Arnica and
control group showed significantly less extent and
intensity of ecchymosis when compared with dexa-
methasone group. Furthermore, no differences in
edema rating were observed among groups at this
time point.
51
Abdominal hysterectomy
Negative results concerning the effect of Arnica 30c
(2 doses preoperatively plus 3 doses postoperatively
for 5 days) on pain, analgesia, infection, and postop-
erative recovery were obtained in a study including
73 women who underwent total abdominal
hysterectomy.
35
Tonsillectomy
Arnica was tested in patients undergoing tonsillec-
tomy. One hundred eleven patients undergoing tonsil-
lectomy were randomized in a double-blind fashion to
receive either Arnica 30c or placebo (2 tablets for 6
times in the first postoperative day followed by 2 tab-
lets twice a day for 7 days).
52
Follow-up over 14 days
after surgery showed a significant reduction in the
VAS pain scores, whereas no difference was observed
in analgesic consumption, complications and return to
normal activities.
Hallux valgus surgery
Arnica 4D (pills; postoperatively 3 times a day for 4
days) was compared with diclofenac sodium 50 mg
(postoperatively 3 times a day for 4 days) in a random-
ized double-blind clinical study in 88 patients under-
going hallux valgus surgery.
53
Arnica 4D and
diclofenac sodium had equivalent efficacy on wound
irritation, patient mobility, and use of analgesics,
whereas Arnica was inferior to diclofenac sodium as
far as VAS pain score was concerned.
Venous surgery
Arnica 5c, administered sublingually the night before
and immediately after saphenous surgery, did not
reduce postoperative hematomas, as evaluated 6 days
postoperatively in a randomized, prospective, multi-
centric double-blind trial involving 130 patients.
37
Aortic valve surgery
Negative results were reported in a double-blind clinical
study involving 90 patients undergoing aortic valve sur-
gery assessing the efficacy of a combination of Arnica 5c
and Bryonia Alba 5c.
47
Five homeopathic granules
administered twice a day for 5 days, starting the even-
ing before surgery for 5 days, did not produce any sig-
nificant change in the volume of blood/liquid in the
drains at their removal and postoperative blood/liquid
losses at 12 and 24 hours as well as C-reactive protein,
pain, temperature, and plasma troponin Ic.
Prolonged venous perfusion
In a double-blind, placebo-controlled clinical study
involving patients undergoing prolonged venous per-
fusion, Arnica 5c reduced pain symptoms, hyperemia,
edema, formation of hematomas and improved blood
flow, as measured by Doppler flowmetry. Arnica treat-
ment also slightly increased a number of coagulation
factors and platelet aggregation.
32
Muscular pain
In a double-blind randomized study involving 82
marathon runners, 5 pills of Arnica 30D, given twice
a day from the evening before until 3 days after the
marathon, improved muscle soreness measured by
VAS immediately after the competition, but it did
not protect from cell damage (creatine kinase, aspar-
tate aminotransferase, alanine aminotransferase,
lactate dehydrogenase, sodium, potassium, magne-
sium, and creatinine were analyzed) measured by
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muscular enzymatic reaction.
41
Contrasting results
were reported in another double-blind randomized
clinical study showing that Arnica 30D did not reduce
muscle soreness after long-distance running in 519
runners, as assessed by VAS and Linkert scale.
36
In
a randomized double-blind trial including 53 patients,
Arnica cream applied immediately after performing
calf raises and 24–48 hours post-exercise also failed to
improve leg pain, motion, and muscle tenderness when
compared with placebo.
46
Dental neuralgia
Arnica was effective for treatment of dental neuralgic
pain after tooth extraction
30
in a placebo-controlled
randomized clinical trial. Arnica 7c (4 granules) and
Hypericum 15c (St John’s wort; 4 granules) prescribed
alternately at 4-hour intervals for 2 days, starting
immediately after clinical examinations, resulted in
pain relief experienced by 76% of patients treated with
homeopathic combination therapy versus 40% of pa-
tients treated with placebo.
Ankle sprains
Arnica tincture spray (41.5 mg) was also tested in com-
bination with hydroxyethyl salicylate (HES; 12.5 mg)
and compared with Arnica (41.5 mg), HES (12.5 mg),
and placebo for treatment of ankle joint distortion-
related pain in a prospective, randomized, double-
blind, 4-arm parallel group phase 4 study including
570 patients.
50
Application of Arnica plus HES 4–5times
daily improved pain assessed by VAS after quickly
walking a distance of approximately10monday3–4.
In summary, this study suggests that Arnica can act syn-
ergistically with other medications such as HES to
reduce sprained ankle joint distortion-related pain.
SAFETY OF ARNICA FORMULATIONS
Although the use of homeopathic medicines is growing,
these compounds are often deemed safe and risk-free
with patients not declaring their use to their general prac-
titioner. Little evidence is available concerning the use of
Arnica in pediatric patients. In this regard, herbal prod-
ucts are extensively used to treat children without con-
sulting the pediatrician and without reporting their use
before a surgical procedure, as showed in a study by
Crowe and Lyons.
54
In this study, the parents of 601
children undergoing ambulatory surgery were asked to
fill in a questionnaire about the administration of herbal
medicines to their children. Sixty-six percent of children
were taking herbal medicines (Arnica and Echinacea were
most commonly used) or had taken them in the past, and
84.7% of parents had not told the practitioner about their
use, without thinking that herbal products could lead to
adverse effects and interact with anesthetic drugs and the
surgical procedure itself. These observations confirm that
homeopathic drugs may be used safely either in general
practice or on self-prescription, although the general
practitioner should be informed to avoid a delay in the
choice of a classic drug treatment, if required. Further
evidence shows that Arnica can be used for external
and internal bruising of both mother and newborn
infant.
55
Furthermore, Arnica has been extensively used
for soft-tissue bruising in a cohort of patients from birth
to 8.5 years of age [Avon Longitudinal Study of Parents
and Children (ALSPAC)].
56
A further study involving
6323 babies showed efficacy and safety of Arnica Echina-
cea powder in the detachment of the umbilical cord
(detachment times: 2 days in 5.12%, 3 days in 44.23%,
4 days in 39.74%, 5 days in 3.20%, 6 days in 3.84%, 7 and
8 days in 1.92%, and 9 days in 0.64%) recommending its
use as routine procedure in all nurseries.
57
As far as safety and adverse events in the adult
population are concerned, Arnica administered topi-
cally is generally well tolerated, particularly as gel for-
mulation.
12,39
Only 1 allergic reaction was reported by
Knuesel et al
39
after topical application of Arnica for
the treatment of mild-to-moderate knee osteoarthritis.
Widrig et al
12
reported side effects occurring only in 5
out of 89 patients receiving Arnica gel for the treatment
of hand osteoarthritis. A further clinical trial of topical
Arnica gel treatment for laser-induced bruises did not
report any adverse reactions.
11
Another report evalu-
ated the irritating and sensitizing potential of Arnica
on 22 subjects without observing any adverse effects.
58
When administered orally, Arnica is safe and well
tolerated only at very low concentrations, such as
those used in homeopathic medicines.
40,59
Therefore,
Arnica’sgood tolerability and efficacy proved that
Arnica in gel formulation, as well as in homeopathic
dilutions for oral use, is an important therapeutic
agent which can be used for pain relief, post-
traumatic edema, and in the postoperative setting.
Furthermore, in certain cases, such as local and gener-
alized pain, the simultaneous administration of topical
and orally administered Arnica, besides being safe and
well tolerated, is indicated
38
because of the therapeutic
synergy created between the two administration
routes. We have summarized the studies reporting
on Arnica side effect profile in Table 2.
DISCUSSION
Over the past twenty years, the use of homeopathic
medicines has increased worldwide in terms of both
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Gchhb by physicians and increased recommen-
dation by pharmacists. In particular, Arnica is one of
the homeopathic remedies used for over 100 years for
the treatment of trauma-associated pain and swelling.
This review summarizes the available preclinical and
clinical evidence concerning the efficacy and safety of
the homeopathic product Arnica in pain-related pro-
cesses. Overall, Arnica (topical and/or oral formula-
tions) has demonstrated reproducible clinical
benefits, some of which are comparable with anti-
inflammatory drugs such as diclofenac,
53
ibupro-
fen
12,60
and corticosteroids
51
which are considered
the therapeutics of choice for the treatment of osteoar-
thritis, postoperative edema, and ecchymosis.
61
Although limited evidence is available for the use of
Arnica in the context of wound healing, a study sug-
gests that it can be used instead of diclofenac after
hallux valgus surgery to reduce wound irritation and
at a lower cost.
53
Furthermore, combined with stinging
nettle, it showed promising results in 2 patients with
grade 2 laser-induced burns.
49
In patients undergoing
the removal of impacted wisdom teeth, Arnica was less
effective for the management of pain and swelling
compared with placebo suggesting that it should not
be used in that clinical condition.
29
These findings sug-
gest that Arnica can be used in the context of wound
healing in selected clinical scenarios. However, the
limited number of studies warrants further investiga-
tions. The topical use of Arnica is supported by studies
evincing its efficacy in relieving acute muscle pain
after excessive exercise,
62
and in the symptomatic
treatment of osteoarthritis.
12,39
The local action is ex-
erted: (1) at the level of the locomotor system on the
muscles, calming the feeling of soreness and pain
63
; (2)
in the joints, reducing the swelling and pain caused by
rheumatic disorders; (3) in the capillaries and veins,
reducing hematoma and ecchymosis and protecting
blood vessels.
20,62
Additionally, Arnica administered
orally in homeopathic dilutions showed positive clin-
ical effects in reducing postoperative pain, swelling,
edema, and ecchymosis.
40,42,51,52
Furthermore, topical
Arnica combined with oral homeopathic dilutions sig-
nificantly reduced postoperative pain.
38
As to topical
gels, this review points out that Arnica has clinical
benefits in relieving pain and surgical complications.
The topical application of Arnica thus offers an alter-
native to ibuprofen because of the high concentration
of sesquiterpenes,
12
and in particular helenalin, which
is the active substance held responsible for its anti-
inflammatory activity.
14
The level of sesquiterpenes
depends on multiple factors. For example, Douglas
et al
64
showed that the total amount of bioactive
endogenous sesquiterpenes varies depending on
which portion of the plant is being used. The
concentration of sesquiterpenes was found to be
higher in the disc florets than in the ray florets, lower
in the receptacle, and even lower in the stalk.
64
This
variability in the quantity of sesquiterpenes, with
a consequent variation in the biological activity, can
influence the clinical efficacy of Arnica.
20
To guarantee
the efficacy of medicines containing Arnica,itisneces-
sary to obtain a phytocomplex with optimal levels of
active substances. This requires the use of high-quality
raw material that is obtained by harvesting whole, fresh
and spontaneously occurring Arnica in its natural hab-
itat, far from any form of pollution and during the bal-
samic phase. Reproducibility is assured by accurate
botanical identification, safeguarding the freshness of
the batch, and performing checks on the raw material
and the finished product. The quality and safety of
homeopathic medicines containing Arnica are guaran-
teed by the European Pharmacopoeia and by specific
Arnica monographs included in the pharmacopoeias of
the individual member states. Pharmaceutical compa-
nies which produce homeopathic medicines containing
Arnica in compliance with these standards are able to
guarantee its efficacy and safety. Specifically, Arnica use
in various clinical settings is achieving a wider reputa-
tion supported by an arising number of open studies,
even if comparison of this compound with traditional
drugs has been rarely performed.
CONCLUSIONS
Cumulative evidence suggests that both Arnica in gel
formulation and in homeopathic dilutions are more
effective than placebo in treating several inflamma-
tory conditions, in pain management and postopera-
tive settings. Its clinical efficacy in these fields and its
high tolerability make it a potential therapeutic alter-
native target to non-steroidal anti-inflammatory
drugs, especially for patients undergoing pharmaco-
logical polytherapy as they are more exposed to the
risk of drug interactions and, consequently, to their
toxicity. The wide variability of formulations and
therapeutic settings precludes a meta-analysis that
could assess the efficacy of specific protocols. Further
trials involving larger cohorts of patients are needed
to support a possible effect of Arnica in several
inflammatory conditions, in pain management and
postoperative settings.
ACKNOWLEDGMENTS
JCMM acknowledges CONACyT-Mexico for its
membership.
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