1952, Dr. Michel Pistor, a generalist practicing in rural France,
administered 10 ml of procaine intravenously in an attempt to abort
an acute asthmatic attack in a patient. While the treatment did
not ameliorate the patient's respiratory status, upon follow-up,
the patient reported a significant improvement in his impaired hearing.
Soon thereafter, Dr. Pistor began experimenting with superficial
injections of procaine around the ear of hearing-impaired patients
and experienced some success. Soon his practice was full of hearing-impaired
patients seeking treatment. His results were mixed, however. Many
of these patients saw improvement in seemingly unrelated concomitant
conditions, such as eczema of the auditory canal and TMJ pain. Additionally,
patients reported improvement with tinnitus, which can be related
to hearing impairment.1
Dr. Pistor continued experimenting with superficial injections of
procaine for the treatment of a spectrum of disorders, and on June
4th of 1958, he published an article describing his clinical success
with this novel procedure in which he stated, "the action on
the tissues originating from the mesoderm is so extensive that these
treatments should be called mesotherapy" (author's translation).
This was the first time the term "mesotherapy" appeared
in print. Dr. Pistor described mesotherapy as, "smallest dose,
infrequently, in the correct location."2
The first international conference on mesotherapy took place in
1976, which was also the year when mesotherapy was first used in
in-patient settings in France. In 1981, Dr. Jacques LeCoz introduced
mesotherapy into the orthopedic clinic at the Institute Nationale
du Sports (National Institute of Sports) in Paris. In 1987, the
French Academy of Medicine officially recognized mesotherapy as
a legitimate treatment modality within conventional medicine.3
Currently, in France, although still viewed as experimental and
unproven, mesotherapy is recognized as a legitimate treatment modality
by the French Academy of Medicine and is reimbursable by their national
social security medical coverage. It has been integrated into France's
largest sports medicine facility4 and is practiced in
a number of pain management centers in France5 as well
as in North Africa.6 Apart from the French Society of
Mesotherapy, some of the more established national mesotherapy associations
or societies are in Algeria, Argentina, Belgium, Brazil, Colombia,
Great Britain, Germany, Greece, Israel, Italy, Mexico, Portugal,
Russia, Switzerland, Spain, Tunisia, Turkey, and Venezuela. Cosmetic
mesotherapy is currently exploding with popularity in Asia, with
new national associations and societies being formed every year.
Basic Tenets of
Mesotherapy is characterized by its unique styles of injection:
various superficial injections, using specialized short needles
and specific techniques, into the epidermis, dermis, and hypodermis
directly over the sites of the affected structures.7 Dr. Pistor
described this treatment as mesotherapy. The mesoderm is one of
the three embryologic histological classifications – namely
endoderm, mesoderm, and ectoderm. The cells of the endoderm morph
primarily into the internal organs. The cells of the mesoderm level
develop into dermis and hypodermis, fatty tissues, and the musculoskeletal
system, and the ectoderm becomes, among other tissues, the brain
and epidermis. The term mesotherapy therefore is in reference to
injecting into those tissues that originate from the mesoderm, namely
the dermis and hypodermis. It is important to understand that the
mesoderm exists only in embryos. Contrary to a current, common erroneous
statement made by English language mesotherapists, there is no mesoderm
layer of the human skin. One is not "injecting into the mesoderm,"
rather one is injecting into those structures that have arisen from
The proposed mechanism of action of mesotherapy is that solutions
injected intracutaneously remain in the area longer than they would
by deeper injection because they are slower to be cleared by general
circulation. Further, it is felt that these solutions injected superficially
continually penetrate into the deeper tissues.
Kaplan and Raincourt injected radioisotope-marked calcitonin and
found, upon serial scans, that the more superficial the injections,
the longer the solution remained in the area.8 LeCoz and DuPont
conducted an experiment on patients scheduled to undergo arthroscopic
surgery of the knee. The subjects were divided into three groups.
The first group received intra-epidermic papules of a diluted non-steroidal
anti-inflammatory drug (NSAID), the second group received sub-cutaneous
injections of the same solution using 4 mm needles, and the third
received deep intramuscular injections of the same solution. At
hours one and three post-injection, venous blood draws were performed
to determine serum levels of the NSAID. It was found that, uniformly,
the more shallow the injection, the lower the level of the substance
present in venous circulation at both one-hour and three-hours post-injection.
During arthroscopy, synovial biopsies were performed, and all groups
were found to have NSAID present, although tissue concentration
levels were not determined.9 Mesotherapy therefore appears to be
a novel technique to administer medicines local to the pathology
while the skin acts as a natural time-release system.
Three principle mesotherapy injecting techniques currently exist:
namely, point by point, nappage (French for "covering"),
Point by point
was first described in the context of mesotherapy by Dr. Pistor.
It is very simply the injection of 0.02cc to 0.05cc of solution
after perpendicularly inserting a 4 mm, 6 mm, or 12 mm needle its
entire depth. Point by point injections are generally given 1-2
cm apart and sparingly.
first described by Bourguignon and Ravily,10 is a more superficial
technique that takes practice to master. With the syringe held at
a 45-degree angle from the skin and while applying light, constant
positive pressure on the syringe's plunger, the practitioner rapidly
flicks the wrist in a way that can mimic the shaking of a salt shaker
or the action of a sewing machine while covering a large area of
skin. Generally, a 4 mm needle is used and is not fully inserted,
only 0.5-2 mm deep, and only a drop of solution is introduced at
each site at approximately 0.25 cm-0.5 cm intervals. In this way,
one is able to infuse a large area of skin with the solution while
achieving a profound cutanous stimulation that mimics certain ancient
acupuncture practices. When performed correctly, one will perform
a "sweep" of nappage, and pinpoint bleeding will occur
five to ten seconds later. Nappage is, without a doubt,the least
comfortable technique for the patient.
first described by Perrin,11 is the most superficial of the techniques.
When performed correctly, the basal layer is not penetrated. Dr.
Perrin developed this technique in 1989 in order to be able to perform
mesotherapy on children without pain. A 13 mm (or half-inch) 27-31
gauge needle is positioned at a very steep angle to the surface
of the skin. Then, with the bevel oriented away from the skin, it
is dragged along the skin while light positive pressure is applied
to the syringe's plunger. The needle will bend slightly from the
angle and the pressure. When treating certain anatomical contours
such as the cervical spine and the occipital ridge, the practitioner
may bend the needle before treating in order to maintain a correct
needle position. Most practitioners will use a slight bouncing action
described as "Parkinsonian."
Epidermic technique is intended to produce a shallow groove in the
uppermost layers of keratinized epithelial cells ,which in turn
is covered with a bead of solution. When performed correctly, there
is no bleeding or scratching, but one is able to see the solution
quickly absorb into the skin. Epidermic technique is done in a grid
pattern at 1 cm intervals over the entire affected area. When either
nappage or epidermic technique are performed, the patient must be
advised to avoid "spray-on tanning" for a minimum of 24
hours post-treatment to avoid a visually bizarre result.
the Treatment of Pain
While the clinical applications of mesotherapy outside the realm
of non-surgical cosmetic medicine are almost entirely unheard of
in the US, in France, the birthplace of mesotherapy, mesotherapy
is first and foremost a pain and sports medicine modality. Mesotherapy
is of particular interest to clinicians due to its safety, tolerability
to patients, cost-effectiveness, and seeming efficacy when compared
to conventional treatment protocols. This discussion is meant to
give an overview of mesotherapy as it is practiced in France for
the treatment of chronic pain and acute injury.
Local anesthetics are used in the vast majority of mesotherapy protocols.
Either lidocaine 1% or procaine 1%, always without epinephrine is
used. Local anesthetics are used for their anesthetic properties
that are believed to be longer-acting when injected mesotherapeutically.
As is taught by the French Society of Mesotherapy, lidocaine is
generally indicated for treatment of acute conditions, while procaine
is indicated for chronic conditions because of its additional vasodilatory
In France, mesotherapists commonly use the vasodilatory medication
buflomedil (Fonzylane) when treating pain. Buflomedil is not available
in the US. Pentoxifylline (Trental), also commonly used in France,
is an FDA-approved medication that is not a true vasodilator but
may be used in place of buflomedil in the US.
Pentoxifylline's on-label use is for the treatment of intermittent
claudication, and it improves microcirculation by decreasing the
blood's viscosity and by improving erythrocyte flexibility. Pentoxifylline
has been shown to increase leukocyte deformability and inhibit neutrophil
adhesion and activation. Tissue oxygen levels have been shown to
significantly increase with therapeutic doses of pentoxifylline
in patients with peripheral arterial disease.13
Mesotherapists believe that, by increasing microcirculation of localized
tissue beds, the elimination of metabolic waste is facilitated,
and there is an increase in the delivery of the mesotherapeutic
solution and oxygen. By injecting pentoxifylline mesotherapeutically,
it is believed to exercise its therapeutic effect for a longer period
of time compared to other routes of administration.14
Pentoxifylline has been shown in animal studies to exert antinociceptive
activities. It is a tumor necrosis factor-alpha and interleukin-1-beta
antagonist,15 and it has been shown to be an interleukin-1-alpha
receptor agonist, which thereby limits inflammatory hyperalgesia.16
Local administration of pentoxifylline causes inhibition of proinflammatory
cytokine synthesis and antagonizes hyperalgesia in formalin-injected
Of particular interest is French mesotherapists' liberal use of
salmon calcitonin (sCT) for the treatment of a broad spectrum of
chronic pain disorders. sCT is best known as an anti-osteoporotic
agent administered as a nasal spray, but its analgesic effects in
the treatment of acute osteoporotic fracture has been well-documented.18-21
Researchers have examined the anti-nocioceptive properties of sCT
for a range of disorders including advanced metastasic malignancy,22-24
reflex sympathetic dystrophy,25 phantom limb pain,26-28 and diffuse
sclerosing osteomyelitis of the humerus.29 One animal study demonstrated
sCT's ability to increase the analgesic effect of amitriptyline
The mechanisms of analgesic action of sCT are believed to be multifactorial.
An anti-inflammatory action has been suggested.31 Studies in animals
and in humans demonstrate that in some, but not all, cases, calcitonin
increases plasma beta-endorphin levels.32 It is possible that specific
binding sites for salmon calcitonin exist in the brain.33
It merits mention that while the clinical use of sCT appears safe,
it is not without risk of side effect or adverse reaction. Nausea
without vomiting and mild local inflammatory reactions at the site
of injection occurs in approximately ten percent of patients receiving
sCT, and transient severe nausea and vomiting occurs in approximately
one in 300 patients. Flushing of face or hands, skin rashes, nocturia,
pruritus of the ear lobes, feverish sensation, pain in the eyes,
poor appetite, abdominal pain, edema of feet, and salty taste have
been reported. Administration of sCT has been reported in isolated
cases to cause hypersensitivity reactions.34
The majority of scientific data in the field of mesotherapy in the
treatment of pain and sports medicine currently are in the French
language and consist of clinical case series. These papers are published
in the journal of the French Society of Mesotherapy, which is not
MedLine-indexed but has been in continual print for 30 years. One
such clinical case series showed mesotherapy to be beneficial in
the treatment of 65 patients suffering from chronic thoracic back
pain from arthritis, spinal stenosis, and sprain/strain not adequately
controlled with conventional methods – namely, NSAIDs, narcotic
analgesics, muscle relaxants, and physiotherapy.35 Another clinician
describes his results of having treated 267 cases of degenerative
arthritic pain and suggests that mesotherapy appears to be an effective
and reasonable treatment option, especially in light of the complete
absence of adverse side effects or reactions in the treatment group.36
One paper describes the mesotherapeutic treatment of 210 patients
with various soft tissue musculoskeletal pain not satisfactorily
controlled with conventional methods. These patients were treated
mesotherapeutically with local anesthetics, NSAIDs, sCT, and a non-sedating
centrally acting muscle relaxant (thiocolchicoside), and the results
suggest mesotherapy to be a reasonably effective treatment option,
especially in light of poor patient toleration to injection of corticosteroids.37
Another paper that describes the use of mesotherapy on 132 cases
of patients with back and neck pain not ameliorated after three
months of conventional treatment also shows mesotherapy to be a
promising treatment option in terms of safety and efficacy.38 Mesotherapy
has been shown to be helpful in a variety of commonly seen sports
medicine conditions, such as Achilles tendonitis.39 Lambert describes
his success in treating 48 cases of Osgood Schlatters.40
A systematic review and descriptive analysis of the current data
and better-constructed large scale trails are needed. However, mesotherapy
appears to be a promising modality in the treatment of a spectrum
of painful disorders. It is of particular interest to clinicians
because of its excellent safety profile, tolerability to the patient,
cost-effectiveness, and seeming efficacy.
In France, a spectrum of condition-specific protocols exists, however,
I encourage those learning mesotherapy for the treatment of pain
to use the following treatment solution. I have presented this formula
to the entire board of directors of the French Society of Mesotherapy,
and they have agreed that this protocol may be considered appropriate
for both acute injury and chronic pain. I teach this protocol as
it consists of ingredients that are at the same time safe, effective,
and readily available internationally:
50IU salmon calcitonin
1cc Pentoxifylline 20mg/mL
1cc lidocaine 2%
0.5cc multivitamin (optional – available as a "meso-multi"
from a number of US compounding pharmacies)
Those interested should view "Mesotherapy
Instructional Text and DVD" to see condition-specific injecting
techniques. For more information, please visit http://www.mesotherapyworldwide.com/Adelson_Training.htm.
1. LeCoz J. Mésothérapie
en Médecine Générale. Ed Masson: 1993.
4. Laurens D. [Suivi traumatologique des perchistes de l'INSEP de
juillet 1998 a juillet 2000.] Presented at the 9th" International
Mesotherapy meeting of the French Society of Mesotherapy, Paris,
October 20-22, 2000. Conference manual. 2000;145-162.
5. Roch FX. [Place de la Mesotherapie dans un centre anit-douleur.]
Presented at the 9th International Mesotherapy meeting of the French
Society of Mesotherapy, Paris, October 20-22, 2000. Conference manual.
6. Belhocine M. Oussedik E. [Dix annees de mesotherapie en traumatologie
du sport au C.N.M.S.] Presented at the 9th International Mesotherapy
conference of the French Society of Mesotherapy, Paris, October
20-22, 2000. Conference manual. 2000;199-206
7. LeCoz, op cit.
8. Kaplan A, Raincour. [Devernir d'un produit marque injecte par
quatre voies differentes.] Bulletin SFM. 1985: 62.
9. LeCoz J, Dupont J-Y. [L'injection en regard du genou par voie
mesotherapique donne de bonnes concentrations intra-articularires.]
Quotidien du Medecin. September
10. Mrejen D, Perrin JJ. Mesotherapie et
Rachis. Editions S.F.M. CERM Ile de France, CRM Champagne,
12. La Pharmacopee en Mesotherapie.
3rd edition. Societe Francaise de Mesotherapie, 2001.
13. Mosby's Drug Consult. St. Louis,
Missouri: Mosby, Inc., an Elsevier Science Company.
14. LeCoz, op cit.
15. Vale ML, et al. Antihyperalgesic effect of pentoxifylline on
experimental inflammatory pain. Br J Pharmacol.
2004 Dec;143(7):833-44. Epub 2004 November 1.
16. Cunha JM. Cytokine-mediated inflammatory hyperalgesia limited
by interleukin-1 receptor antagonist. Br
J Pharmacol. 2000 Jul;130(6):1418-24.
17. Dorazil-Dudzik M, et al. The effects of local pentoxifylline
and propentofylline treatment on formalin-induced pain and tumor
necrosis factor-alpha messenger RNA levels in the inflamed tissue
of the rat paw. Anesth Analg. 2004
18. Gennari C. Analgesic effect of calcitonin in osteoporosis. Bone.
2002 May;30(5 Suppl):67S-70S.
19. Silverman SL, Azria M. The analgesic role of calcitonin following
osteoporotic fracture. Osteoporos Int.
20. Lyritis GP, Ioannidis GV, Karachalios T, Roidis N, Kataxaki
E, Papaioannou N, Kaloudis J, Galanos A. Analgesic effect of salmon
calcitonin suppositories in patients with acute pain due to recent
osteoporotic vertebral crush fractures: a prospective double-blind,
randomized, placebo-controlled clinical study. Clin
J Pain. 1999 Dec;15(4):284-9.
21. Mehta NM, Malootian A, Gilligan JP. Calcitonin for osteoporosis
and bone pain. Curr Pharm Des. 2003;9(32):2659-76.
22. Allan E. Calcitonin in the treatment of intractable pain from
advanced malignancy. Pharmatherapeutica.
23. Mystakidou K, Befon S, Hondros K, Kouskouni E, Vlahos L. Continuous
subcutaneous administration of high-dose salmon calcitonin in bone
metastasis: pain control and beta-endorphin plasma levels. J
Pain Symptom Manage. 1999 Nov;18(5):323-30.
24. Szanto J, Jozsef S, Rado J, Juhos E, Hindy I, Eckhardt S. Pain
killing with calcitonin in patients with malignant tumours. Oncology.
25. Appelboom T. Calcitonin in reflex sympathetic dystrophy syndrome
and other painful conditions. Bone.
2002 May;30(5 Suppl):84S-86S.
26. Wall GC, Heyneman CA. Calcitonin in phantom limb pain. Ann
Pharmacother. 1999 Apr;33(4):499-501.
27. Simanski C, Lempa M, Koch G, Tiling T, Neugebauer E. [Therapy
of phantom pain with salmon calcitonin and effect on postoperative
patient satisfaction.] Chirurg.
28. Jaeger H, Maier C. Calcitonin in phantom limb pain: a double-blind
study. Pain. 1992; 48:21–27.
29. Donnelly S, Doyle DV. Chronic diffuse sclerosing osteomyelitis
of the humerus: novel treatment with calcitonin. J
Rheumatol. 1993 Jun;20(6):1073-6.
30. Ormazabal MJ, Goicoechea C, Sanchez E, Martin MI. Salmon calcitonin
potentiates the analgesia induced by antidepressants. Pharmacol
Biochem Behav. 2001 Jan;68(1):125-33.
31. Azria M. Possible mechanisms of the analgesic action of calcitonin.
Bone. 2002 May;30(5 Suppl):80S-83S.
32. Franceschini R, Cataldi A, Cianciosi P, Garibaldi A, Corsini
G, Barreca T, Rolandi E. Calcitonin and beta-endorphin secretion.
Biomed Pharmacother. 1993;47(8):305-9.
33. Lyritis GP, Trovas G. Analgesic effects of calcitonin. Bone.
2002 May;30(5 Suppl):71S-74S.
34. Mosby's Drug Consult, op cit.
35. Smail H. [Douleurs thoraciques anterieures d'origine vertebrale.]
Presented at 9th International Mesotherapy conference held by the
French Society of Mesotherapy, Paris, October 20-22, 2000.
36. Leah da Silva J, Mesquita ME. [Resultants de l'evaluation de
deux annees de traitemment de la douleur par mesotherapie dans les
rhumatismes degeneratifs chroniques.] Presented at 9th International
Mesotherapy conference held by the French Society of Mesotherapy,
Paris, October 20-22, 2000.
37. Chos D. [Enquete retrospective des tendino-myalgies du rachis
rencontrees dans une consultation de rhumatologue dans le cadre
d'n centre anti douleur.] Presented at 9th International Mesotherapy
conference held by the French Society of Mesotherapy, Paris, October
38. Messedi-Kamoun N, Ben Salah FZ, Dziri C. [La Mesotherapie dans
les douleurs rachidiennes experience Tunisienne a propos de 132
cas.] Presented to 9th international mesotherapy conference held
by the French Society of Mesotherapy, Paris, October 20-22, 2000.
39. Bourit G, Guerin P. [Propositions therapeutiques dans la pathologie
du tendon calcaneen. Presented in 9th International Mesotherapy
conference held by the French Society of Mesotherapy, Paris, October
40. Lambert Y. [Place de las mesotherapie dans le concert therapeutique
de la douleur chronique.] Lave Revue de Mesotherapie. 2000;1.