21P H A R M A C Y

French Mesotherapyfor the Treatment of Pain

Harry Adelson, ND 2005

The clinical applications of mesotherapy outside the realmof nonsurgical cosmetic medicine are almost entirely unheardof in the United States. However, in France, the birthplace ofmesotherapy, it is first and foremost a pain and sports medicinemodality. Mesotherapy is of particular interest to clinicians dueto its safety, tolerability, cost effectiveness and seeming efficacywhen compared to conventional treatment protocols. This dis-cussion is intended to provide an overview of mesotherapy as itis practiced in France for the treatment of chronic pain andacute injury.

History of MesotherapyIn 1952, Dr. Michel Pistor, a generalist practicing in rural France,

administered 10 mL of procaine intravenously in an attempt to abortan acute asthma attack in a patient. While the treatment did notameliorate the patient’s respiratory status, upon follow-up, the pa-tient reported a significant improvement in his impaired hearing. Soonthereafter, Dr. Pistor began experimenting with superficial injectionsof procaine around the ears of hearing-impaired patients and experi-enced some success. Soon his practice was full of hearing-impairedpatients seeking treatment. His results were mixed. However, manyof these patients saw improvement in seemingly unrelated conditionssuch as eczema of the auditory canal and temporomandibular joint(TMJ) pain. In addition, patients reported improvement in tinnitus,which can be related to hearing impairment.1

Dr. Pistor continued experimenting with superficial injections ofprocaine for the treatment of a variety of disorders. On June 4, 1958,he published an article describing his clinical success with this novelprocedure in which he stated, “the action on the tissues originatingfrom the mesoderm is so extensive that these treatments should becalled mesotherapy” (author’s translation). This was the first timethe term “mesotherapy” appeared in print. Dr. Pistor described me-sotherapy as “smallest dose, infrequently, in the correct location.” 2

The mesoderm is one of the three embryologic, histological classi-fications-- endoderm, mesoderm and ectoderm. The cells of the endo-derm develop primarily into the internal organs while the cells of themesoderm level develop into dermis and hypodermis, fatty tissuesand the musculoskeletal system. The ectoderm becomes, among othertissues, the brain and epidermis. The term “mesotherapy” thereforerefers to injections into the dermis and hypodermis, which originate

from the mesoderm. As will be discussed later, one mesotherapytechnique developed after Dr. Pistor’s 1958 paper involves injectingthe epidermis, which originates from the ectoderm. However, it isimportant to note that the mesoderm exists only in embryos; there isno mesoderm layer of the human skin--a statement commonly madein error by English language mesotherapists. One is not “injectinginto the mesoderm.” Rather, one is injecting into those structures thathave arisen from mesoderm.

The first international conference on mesotherapy took place in1976—also the year in which mesotherapy was first used in inpa-tient settings in France. In 1981, Dr. Jacques Le Coz introducedmesotherapy into the orthopedic clinic at the Institue Nationale duSports (National Institute of Sports) in Paris. In 1987, the FrenchAcademy of Medicine officially recognized mesotherapy as a legiti-mate treatment modality within conventional medicine.3

Currently in France, although still viewed as experimental andunproven, mesotherapy is recognized as a legitimate treatmentmodality by the French Academy of Medicine and is reimbursableby that country’s national social security medical coverage. It hasbeen integrated into France’s largest sports medicine facility4 andis practiced in a number of pain management centers in France5 aswell as in North Africa6 . Apart from the French Society of Meso-therapy, some of the more established national mesotherapy asso-ciations or societies can be found in Algeria, Argentina, Belgium,Brazil, Colombia, Great Britain, Germany, Greece, Israel, Italy,Mexico, Portugal, Russia, Switzerland, Spain, Tunisia, Turkeyand Venezuela. The popularity of cosmetic mesotherapy is cur-rently exploding in Asia, with new national associations and soci-eties being formed every year.

Basic tenants of mesotherapyMesotherapy is characterized by its unique styles of injection--

various superficial injections using specialized short needles and spe-cific techniques directly over the sites of the affected structures.7 Theproposed mechanism of action of mesotherapy is that solutions thatare injected intracutaneously remain in the area longer than they wouldif delivered via deeper injection because they are cleared moreslowly by the general circulation. In addition, it is felt that thesesuperficially injected solutions continue to penetrate into the deepertissues. Kaplan and Raincourt injected radioisotope-marked calci-

A CLINICIAN’S VIEWPOINT

A CLINICIAN’S VIEWPOINT

22 A M E R I C A N J O U R N A L O F M E S O T H E R A P Y

tonin and found, upon serial scans, that the more superficial theinjections, the longer the solution remained in the area.8 Le Coz andDuPont conducted an experiment on patients scheduled to undergoarthroscopic surgery of the knee. The subjects were divided intothree groups. The first group received intraepidermic papules of adiluted NSAID, the second group received subcutaneous injectionsof the same solution using 4-mm needles, and the third receiveddeep intramuscular injections of the same solution. At 1 and 3 hourspost injection, venous blood draws were performed to determineserum levels of the NSAID. It was found that uniformly, the shal-lower the injection, the lower the level of the substance present invenous circulation at both 1 and 3 hours post injection. Duringarthroscopy, synovial biopsies were performed and all groups werefound to have NSAID present, though tissue concentration levelswere not determined.9 Mesotherapy therefore appears to be a noveltechnique for administering medicines locally to the area of thepathology with the skin acting as a natural time-release system.

There are currently three principal mesotherapy injecting tech-niques--point by point, nappage (French for “covering”) and epider-mic. Point by point was first described in the context of mesotherapyby Dr. Pistor. It is very simply the injection of 0.02 cc to 0.05 cc ofsolution after perpendicularly inserting a 4-mm,

6-mm or 12-mm needle its entire depth. Point-by-point injec-tions are generally given 1 cm to 2 cm apart and sparingly. Nappage,first described by Bourguignon and Ravily10, is a more superficialtechnique that takes practice to master. With the syringe held at a45-degree angle from the skin and while applying light, constantpositive pressure on the syringe’s plunger, the practitioner rap-idly flicks the wrist (which can mimic shaking a salt shaker or theaction of a sewing machine) while covering a large area of skin.Generally a 4-mm needle is used and is not fully inserted, perhapsonly 0.5 mm to 2 mm deep, and only a drop of solution is intro-duced at each site at approximately 0.25-cm to 0.5-cm intervals.In this way, one is able to infuse a large area of skin with thesolution while achieving a profound cutanous stimulation thatmimics certain ancient acupuncture practices. When done correctly,the practitioner performs a “sweep” of nappage. Pinpoint bleed-ing occurs 5 to 10 seconds later. Nappage is without a doubt theleast comfortable technique for the patient. The third technique isepidermic, first described by Perrin.11 As the name implies, this isthe most superficial of the techniques. When performed correctly,the basal layer is not penetrated. Dr. Perrin developed this tech-nique in 1989 so that he could perform mesotherapy on childrenwithout pain, after a minor mishap treating his daughter for asinus infection. A 13-mm (or ½-inch) 27- to 31-gauge needle ispositioned at a very steep angle to the surface of the skin, then,with the bevel oriented away from the skin, it is dragged along theskin while light, positive pressure is applied to the syringe’splunger. The needle will bend slightly from the angle and the pres-sure. When treating certain anatomical contours such as the cervi-cal spine and the occipital ridge, the practitioner may bend theneedle before treating in order to maintain a correct needle posi-tion. Most practitioners will use a slight bouncing action describedas “Parkinsonian.” The epidermic technique is intended to pro-

duce a shallow groove in the uppermost layers of keratinized epi-thelial cells which in turn is covered with a bead of solution. Whenperformed correctly, there is no bleeding or scratching but one isable to see the solution quickly absorb into the skin. Epidermictechnique is done in a grid pattern at 1-cm intervals over the entireaffected area. When either nappage or epidermic technique isperformed, the patient must be advised to avoid “spray-on tan-ning” for a minimum of 24 hours post treatment.

Local anesthetics are used in the vast majority of mesotherapyprotocols--either lidocaine 1% or procaine 1%--always without epi-nephrine. Local anesthetics are used for their anesthetic propertiesthat are believed to be longer acting when injectedmesotherapeutically. As is taught by the French Society of Meso-therapy, lidocaine is generally indicated for the treatment of acuteconditions, while procaine is indicated for chronic conditions be-cause of its additional vasodilatory properties.12

In France, mesotherapists commonly use the vasodilatory medi-cation Fonzylane (buflomédil) when treating pain. Trental®(pentoxifylline), also commonly used in France, is an FDA-ap-proved medication that is not a true vasodilator but may be usedin the place of buflomédil in the United States. The approved usefor pentoxifylline is for the treatment of intermittent claudication.The drug improves microcirculation by decreasing the blood’s vis-cosity and by improving erythrocyte flexibility. Pentoxifyllinehas been shown to increase leukocyte deformability and inhibitneutrophil adhesion and activation. Tissue oxygen levels have beenshown to significantly increase with therapeutic doses ofpentoxifylline in patients with peripheral arterial disease.13

Mesotherapists believe that by increasing microcirculation of lo-calized tissue beds, the elimination of metabolic waste is facili-tated. Injecting pentoxifylline mesotherapeutically is believed toexercise the drug’s therapeutic effect for a longer period of timecompared to other routes of administration.14

Pentoxifylline has been shown in animal studies to demonstrateantinociceptive activity. It is a tumor necrosis factor-alpha andinterleukin-1-beta antagonist.15 It has been shown to be an interleukin-1alpha receptor agonist which therefore limits inflammatory hyper-algesia.16 Local administration of pentoxifylline causes inhibition ofproinflammatory cytokine synthesis and antagonizes hyperalgesia informalin-injected rats.17

Of particular interest is French mesotherapists’ liberal use ofsalmon calcitonin (sCT) for the treatment of a broad range ofchronic pain disorders. Salmon calcitonin is best known as anantiosteoporotic agent administered as a nasal spray, but its an-algesic effects in the treatment of acute osteoporotic fracturehave been well documented.18-21 Researchers have examinedthe anti-nocioceptive properties of sCT for a range of disordersincluding advanced metastatic malignancy22-24, reflex sympa-thetic dystrophy25, phantom limb pain26-28 and diffuse scle-rosing osteomyelitis of the humerus29. One animal study dem-onstrated sCT’s abilty to potentiate the analgesic effect of ami-triptyline and paroxetine30.

23A CLINICIAN’S VIEWPOINT

The mechanisms of analgesic action of sCT are believed to bemultifactorial. An anti-inflammatory action has been suggested31.Studies in animals and in humans demonstrate that, in some butnot all cases, calcitonin increases plasma beta-endorphin lev-els32. It is possible that specific binding sites for salmon calci-tonin exist in the brain33.

It‘s worth mentioning that while the clinical use of sCT appearssafe, it is not without risk of side effects or adverse reactions. Nauseawithout vomiting and mild local inflammatory reactions at the site ofinjection are encountered in approximately 10% of patients receivingsCT and transient severe nausea and vomiting occurs in approxi-mately 1 in 300 patients. Flushing of the face or hands, skin rashes,nocturia, pruritus of the ear lobes, feverish sensation, pain in theeyes, poor appetite, abdominal pain, edema of the feet and salty tastehave been reported in patients treated with salmon calcitonin. Ad-ministration of sCT has been reported in isolated cases to causehypersensitivity reaction34.

The majority of scientific data on mesotherapy in sports medicineand for the treatment of pain are currently written in French andconsist of clinical case studies. These papers are published in thejournal of the French Society of Mesotherapy, which is not Medlineindexed but which has been published for

30 years. One such clinical case study showed mesotherapy tobe beneficial in the treatment of 65 patients suffering from chronicthoracic back pain due to arthritis, spinal stenosis and sprain/strainthat was inadequately controlled using conventional methods,namely, NSAIDs, narcotic analgesics, muscle relaxants and physio-therapy35. Another clinician describes his results after treating 267cases of degenerative arthritic pain and suggests that mesotherapyappears to be an effective and reasonable treatment option, espe-cially in light of the complete absence of adverse events or reactionsin the treatment group36. One paper describes the mesotherapeutictreatment of 210 patients with soft tissue musculoskeletal pain notsatisfactorily controlled with conventional methods. These patientswere treated mesotherapeutically with local anesthetics, NSAIDs,sCT and a nonsedating, centrally acting muscle relaxant(thiocolchicoside). The results suggest mesotherapy to be a reason-ably effective treatment option, especially in light of poor patienttolerance of the commonly used interventive option--injection ofcorticosteroids37. Another paper which describes the use of meso-therapy in 132 cases of patients with back and neck pain that hadnot been ameliorated by at least 3 months of conventional treatmentalso shows mesotherapy to be a promising treatment option interms of safety and efficacy38. Mesotherapy has been shown to behelpful in a variety of commonly seen sports medicine conditionssuch as Achilles tendonitis39. Lambert describes his success in treat-ing 48 cases of Osgood-Schlatter’s40.

A systematic review and descriptive analysis of the current dataand better constructed, large scale trails are needed. However, meso-therapy appears to be a promising modality in the treatment of avariety of painful disorders. It is of particular interest because of itsexcellent safety profile, tolerability to the patient, cost effectivenessand seeming efficacy.

1. Le Coz, Mesotherapie in Medecine Generale, Masson, 1993.2. Le Coz, Mesotherapie in Medecine Generale, Masson, 1993.3. Le Coz, Mesotherapie in Medecine Generale, 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 Societyof Mesotherapy, Paris, October 20-22nd, 2000, pp145-162 of the conference manual.

5. Roch, F.X., “Place de la Mesotherapie dans un centre anit-douleur”, presented at the9th international mesotherapy meeting of the French Society of Mesotherapy, Paris,October 20-22nd, 2000, pp53-63 of the conference manual.

6. Belhocine, M. Oussedik, E. “Dix annees de mesotherapie en traumatologie du sportau C.N.M.S”. presented at the 9th international mesotherapy conference of the FrenchSociety of Mesotherapy, Paris, October 20-22nd, 2000, pp 199-106 of the confer-ence manual.

7. Le Coz, Mesotherapie in Medecine Generale, Masson, 1993.8. Kaplan A, Raincour. –Devernir d’un produit marque injecte par quatre voies

differentes, Bulletin SFM, 1985, p62.9. Le Coz J., Dupont J.-Y. _ L’injection en regard du genou par voie mesotherapique

donne de bonnes concentrations intra-articularires. Quotidien du Medecin, Sep-tember 20th, 1983.

10. Mrejen, D. Perrin, J.J. Mesotherapie et Rachis, Editions S.F.M. CERM Ile de France,CRM Champagne, 2003.

11. Mrejen, D. Perrin, J.J. Mesotherapie et Rachis, Editions S.F.M. CERM Ile de France,CRM Champagne, 2003.

12. La Pharmacopee en Mesotherapie, Societe Francaise de Mesotherapie, 3rd edition, 200113. Mosby's Drug Consult, Mosby, Inc. An Elsevier Science Company, St. Louis, Missouri.14. Le Coz, Mesotherapie in Medecine Generale, Masson, 1993.15. Vale ML et al., “Antihyperalgesic effect of pentoxifylline on experimental inflamma-

tory pain”, Br J Pharmacol. 2004 Dec;143(7):833-44. Epub 2004 Nov 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 RNAlevels in the inflamed tissue of the rat paw. Anesth Analg. 2004 Jun;98(6):1566-73.

18. Gennari C. Analgesic effect of calcitonin in osteoporosis. Bone. 2002 May;30(5Suppl ) :67S-70S.

19. Silverman SL, Azria M. The analgesic role of calcitonin following osteoporoticfracture. Osteoporos Int. 2002 Nov;13(11):858-67.

20. Lyritis GP, Ioannidis GV, Karachalios T, Roidis N, Kataxaki E, Papaioannou N,Kaloudis J, Galanos A. Analgesic effect of salmon calcitonin suppositories in pa-tients with acute pain due to recent osteoporotic vertebral crush fractures: a pro-spective 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. 1983;3(7):482-6.

23. Mystakidou K, Befon S, Hondros K, Kouskouni E, Vlahos L. Continuous subcu-taneous administration of high-dose salmon calcitonin in bone metastasis: paincontrol and beta-endorphin plasma levels. J Pain Symptom Manage. 1999Nov ;18 (5 ) :323 -30 .

24. Szanto J, Jozsef S, Rado J, Juhos E, Hindy I, Eckhardt S. Pain killing with calcitoninin patients with malignant tumours. Oncology. 1986;43(2):69-72.

25. Appelboom T. Calcitonin in reflex sympathetic dystrophy syndrome and other pain-ful conditions., Bone. 2002 May;30(5 Suppl):84S-86S.

26. Wall GC, Heyneman CA. Calcitonin in phantom limb pain. Ann Pharmacother. 1999Apr ;33(4 ) :499-501 .

27. Simanski C, Lempa M, Koch G, Tiling T, Neugebauer E. [Therapy of phantom painwith salmon calcitonin and effect on postoperative patient satisfaction] Chirurg.1999 Jun;70(6):674-81

28. Jaeger H, Maier C. Calcitonin in phantom limb pain: a doubleblind study. Pain1992; 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 potentiatesthe analgesia induced by antidepressants. Pharmacol Biochem Behav. 2001Jan;68(1) :125-33.

31. Azria M. Possible mechanisms of the analgesic action of calcitonin. Bone. 2002May;30(5 Suppl):80S-83S.

32. Franceschini R, Cataldi A, Cianciosi P, Garibaldi A, Corsini G, Barreca T, Rolandi E.Calcitonin and beta-endorphin secretionBiomed Pharmacother. 1993;47(8):305-9.

33. Lyritis GP, Trovas G. Analgesic effects of calcitonin. Bone. 2002 May;30(5Supp l ) :71S-74S

34. Mosby's Drug Consult, Mosby, Inc. An Elsevier Science Company, St. Louis, Missouri35. Smail, H. Douleurs thoraciques anterieures d’origine vertebrale, 9th international meso-

therapy conference held by the French Society of Mesotherapy, Paris, October 20-22nd, 2000.36. Leah da Silva, J., Mesquita, M.E. resultants de l’evaluation de deux annees de

traitemment de la douleur par mesotherapie dans les rhumatismes degeneratifschroniques, 9th international mesotherapy conference held by the French Societyof Mesotherapy, Paris, October 20-22nd, 2000.

37. Chos, D. Enquete retrospective des tendino-myalgies du rachis rencontrees dansune consultation de rhumatologue dans le cadre d’n centre anti douleur. 9th inter-national mesotherapy conference held by the French Society of Mesotherapy, Paris,October 20-22nd, 2000.

38. Messedi-Kamoun, N., Ben Salah F.Z., Dziri, C. La Mesotherapie dans les douleursrachidiennes experience Tunisienne a propos de 132 cas. 9th international meso-therapy conference held by the French Society of Mesotherapy, Paris, October 20-22nd, 2000.

39. Bourit, G. Guerin, P. Propositions therapeutiques dans la pathologie du tendoncalcaneen, 9th international mesotherapy conference held by the French Society ofMesotherapy, Paris, October 20-22nd, 2000.

40. Yves Lambert, Place de las mesotherapie dans le concert therapeutique de la douleurchronique, Lave Revue de Mesotherapie, vol 1, 2000.