EP0679090A1 - Procede de traitement du syndrome de costen - Google Patents

Procede de traitement du syndrome de costen

Info

Publication number
EP0679090A1
EP0679090A1 EP94906673A EP94906673A EP0679090A1 EP 0679090 A1 EP0679090 A1 EP 0679090A1 EP 94906673 A EP94906673 A EP 94906673A EP 94906673 A EP94906673 A EP 94906673A EP 0679090 A1 EP0679090 A1 EP 0679090A1
Authority
EP
European Patent Office
Prior art keywords
muscle
pain
agent
patient
syndrome
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP94906673A
Other languages
German (de)
English (en)
Inventor
Gary E. Borodic
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
INTERACTIVE BIOLOGICS ASSOCIATES
Original Assignee
Interactive Biologics Associates
Associated Synapse Biologics
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Interactive Biologics Associates, Associated Synapse Biologics filed Critical Interactive Biologics Associates
Publication of EP0679090A1 publication Critical patent/EP0679090A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the invention relates to a method for treating the symptoms of myofascial pain syndrome by specific partial, reversible chemical denervation of the myofascial pain source.
  • Myofascial pain syndrome is a chronic pain condition with often widespread pain complaints, trigger points and tender points.
  • Trigger points in particular are characteristic of the syndrome.
  • a trigger point is an area which, when pressed by a pressure gauge or finger, produces pain in a distribution in which the symptoms appear to occur.
  • Tender points are areas of the muscle that, when pressed, create pain at the site of compression. Tender points differ from trigger points in that pressure on a tender point does not reproduce or "trigger" the distribution of pain associated with the original complaint.
  • Muscles afflicted with myofascial pain often demonstrate tender tight bands upon palpation. The pain is usually localized to the muscular area and is not associated with tenderness over bone articulation or anatomic areas occupied by tendon structures.
  • Myofascial syndrome sometimes is misdiagnosed as fibromyalgia or fibrositis syndrome. These terms in older literature may have been interchangeable with chronic muscular pain; therefore, myofascial pain sometimes can be viewed as localized fibromyalgia.
  • Fibromyalgia is a generalized syndrome characterized by tenderness within diffuse distribution of muscle groups and associated systemic complaints such as sleep disturbances, generalized fatigue, chronic headaches and irritable bowel symptoms. These characteristics distinguish it from myofascial pain syndrome.
  • Localized fibromyalgia also has been referred to as "fibrositis", which may be considered almost the same as fibromyalgia.
  • a palpable trigger point is essential to the diagnosis of myofascial pain syndrome.
  • Pain referred from the trigger point is usually described as a subcutaneous location with slightly blurred edges; 2.
  • Several muscles including the deltoid, gluteus maximus, oseratus posterior/inferior) refer pain locally in the immediate vicinity of the trigger point;
  • Trigger points in the limb muscles refer pain distally rather than proximally;
  • Pain occurring in certain muscles is referred into adjacent joints, occasionally mimicking arthritis
  • Aching pain in the pltysma muscle secondary to myofascial causes is described as a "prickling" sensation
  • Trigger points may refer hypesthesia (numbness) or anesthesia instead of pain.
  • Myofascial pain syndrome often is associated with reduced range of motion. The pain complaint can be reproduced by digital pressure or by needle penetration of the trigger point. Pain is thought to be caused by unusual tension, tone and afferent receptors within muscle which carry the impulse perception of pain. These pain receptors have been termed “nociceptors. " Nociceptors are microanatomic elements within muscle which sense stretch and perhaps pain. Myofascial pain syndrome can be a cause of post ⁇ operative pain. For example, myofascial pain syndrome may arise after temporomandibular joint surgery or acoustic neuroma surgery.
  • Myofascial pain is specifically distinguishable from pain arising from joint and bone by the absence of arthritis or other forms of joint pathology, as demonstrated on routine radiographs, computerized tomography (CT) or magnetic resonance imaging (MRI).
  • CT computerized tomography
  • MRI magnetic resonance imaging
  • the trigger points in myofascial pain are clearly within the palpable body of the muscle. Tight bands are palpable in muscles demonstrating this particular syndrome, which often are associated with trigger points. Electrophysiologic measurement of changes at the trigger points have been attempted, but the results have not been consistent. Durett et al.. Am J Phys Med Rehabil, 70(3) :154-156 (1991); Fricton et al. , Arch Phys Med Rehabil, 66(5) ;314-317 (1985)
  • the following represents a summary of clinical criteria for diagnosing myofascial pain syndrome caused by active trigger points.
  • the five major criteria include:
  • the history of therapy for myofascial syndrome has included the use of oral analgesics such as aspirin and acetominophen, the use of non-steroidal anti- inflammatory systemic drugs such as ibuprofen, injection of a local anesthetic such as LidocaineTM , physical therapy, biofeedback, and use of sensory stimulating devices such as acupuncture or TENS units for blocking sensory pain and reducing immobilization.
  • oral analgesics such as aspirin and acetominophen
  • non-steroidal anti- inflammatory systemic drugs such as ibuprofen
  • injection of a local anesthetic such as LidocaineTM
  • physical therapy such as a local anesthetic
  • biofeedback a local anesthetic
  • sensory stimulating devices such as acupuncture or TENS units for blocking sensory pain and reducing immobilization.
  • the present invention relates to a method for alleviating pain and other symptoms associated with myofascial pain syndrome.
  • the method comprises administering locally to a muscle of the patient affected by the syndrome an amount of a chemodenervating agent sufficient to alleviate the symptoms of the syndrome, wherein the chemodenervating agent deactivates impulse transmission at the neural motor endplates in the muscle.
  • the present method provides localized relief from myofascial pain which is sustained over a period of time.
  • the invention in another aspect, relates to producing an analgesic effect in a patient experiencing myofascial pain by administering locally to a muscle of the patient an analgesically effective amount of the chemodenervating agent.
  • the analgesic effect so produced is sustained for a prolonged period of time, e.g., for at least 7 days, generally for between 2 and 12 weeks, and up to as long as about 16 weeks.
  • Chemodenervating agents useful in the present invention are agents which specifically block release of acetylcholine from the neural motor end plates of the treated muscle.
  • Botulinum-derived toxins are preferred agents for this purpose.
  • Botulinum toxins block release of acetylcholine from neural motor endplates, resulting in induction of muscle fiber atrophy and muscle weakness, while retaining muscle function.
  • Botulinum toxin affects the axonal terminal of motor nerves without having any known effect on the sensory nervous system.
  • collateral axonal sprouting accour, and new neuromuscular junctions are established in the muscle, generally over a 10 to 12 week period.
  • the effects of botulinum toxin are temporary and generally run a course of about 12 weeks. After the twelve week period, normal innervation returns to the muscle and there is regeneration of muscle fiber size. Another round of treatment can be administered at this time, if necessary or desirable.
  • a therapeutic amount of a botulinum toxin preparation is administered locally to a muscle of a patient suffering from myofascial pain syndrome.
  • the toxin preparation is injected directly into the muscle or muscles affected by the syndrome.
  • a dose in the range of from about 5 to about 1000 IU of botulinum-derived toxin generally is effective for this purpose.
  • the present method provides a therapy which confers localized, sustained relief from myofascial pain over a period of several weeks or months.
  • the method has several advantages over traditional treatments for myofascial pain. For example, it avoids the need for surgery or other invasive procedures, which carry considerable risk, and avoids the use of systemic drugs, which may have undesirable side effects.
  • Chemodenervating pharmaceuticals such as botulinum toxin
  • central nervous system functions such as cognitive reasoning, sleep patterns, appetite, affective disposition or other central nervous system functions.
  • the present invention is distinctly different from all prior therapies in that blockage of neuromuscular transmission is the only effect of the toxin without sensory and neural effects. Reduction in tone, resting tension, and contractility in the muscle creates a secondary effect at the nociceptors resulting in decreased afferent "pain" output to the central nervous system.
  • the present method provides a therapeutic treatment for alleviating pain having a myofascial origin by chemically inducing denervation of a muscle or muscles.
  • myofascial refers to a sheet of fibrous tissue (the "fascia") which encloses muscles or groups of muscles and separates muscular layers or groups.
  • Myofascial pain syndrome is a well-defined syndrome having a characteristic set of symptoms, as set out in detail hereinabove.
  • the term “myofascial pain syndrome” may include disorders diagnosed as localized fibromyalgia or localized fibrositis. The term is intended to include any disorders which meet the diagnostic criteria characteristic of myofascial pain syndrome.
  • the present method involves administering to a muscle of a patient afflicted with myofascial pain syndrome an amount of a chemical denervating agent which specifically denervates the neural motor endplates in the muscle sufficient to alleviate the pain symptoms.
  • the present method produces a localized, sustained analgesic effect in a patient experiencing myofascial pain by administering locally to the afflicted muscle or muscles an analgesically effective amount of a chemical denervating agent sufficient to denervate neural motor endplates of the afflicted muscle.
  • Chemical denervating agents which are effective for this purpose are agents which specifically denervate neural motor endplates of the affected muscles, for example, by blocking the release of acetylcholine from the endplates.
  • the chemical denervating agent induces a number of changes in the muscle, including diffuse muscular atrophy, elongation of muscle fiber units and a decrease in the output of afferent impulses from the treated muscle. Injection of the denervating agent causes the treated muscle to loosen and elongate and decreases its resting tone, thereby increasing the amount of passive stretch in the muscle. Without wishing to be bound by theory, it is believed that decreasing the resting tone within muscle by chemodenervation reduces the afferent impulses transmitted to the central nervous system.
  • the chemical denervating agent loosens muscle tone and contractility which in turn influences nociceptors in the affected muscles, thereby blocking transmission of the pain impulses.
  • the effects of the denervating agent are sustained for a period of time which can be influenced by several factors, including the amount of the agent administered, it's extent of diffusion in the muscle, the amount and type of diluent and the patient's individual reaction to the agent. The effect in most patients will last for at least 7 days, and typically up to about 12 weeks, thus affording prolonged pain relief.
  • Botulinum toxins are a family of toxins derived from Clostridium botulinum. There are seven known serotypes of botulinum toxins, designated types A through G. Pharmaceutical grade type A toxin is commercially available from Allergan Pharmaceuticals, Inc. under the tradename Oculinum . However, the method of the invention can be practiced using any physiologically acceptable injectable substance which interrupts neuromuscular transmission at the neuromuscular junction.
  • the chemodenervating agents of this invention can be processed in accordance with conventional methods of pharmacy to produce medicinal agents for administration to patients, e.g., humans.
  • the agents typically are employed in admixture with conventional excipients and/or diluents, i.e., pharmaceutically acceptable carrier substances suitable for injection which do not deleteriously affect the active agent.
  • suitable carriers include, but are not limited to, water, salt solutions, and physiologic buffers. For parenteral application, injectable sterile solutions are preferred.
  • the agent can be administered by any method suitable for locally administering a drug, including, for example, transdermal diffusion, transcutaneous injection, intramuscular injection or implantation of a device which releases the substance into the desired area.
  • Transcutaneous injection directly into the afflicted muscle is the preferred method.
  • a botulinum toxin preparation is injected into a muscle of a patient afflicted with myofascial pain syndrome. Injection of a botulinum toxin preparation into the muscle deposits a bolus of the material at the injection point which diffuses outwardly. The distance of diffusion is not clearly understood and seems to depend upon a number of factors, including the nature and amount of diluent, the mass of the toxin molecule, the population of presynaptic receptors about the site of the injection and the physiological condition of the patient.
  • the therapeutic and analgesic effects are achieved at dosage levels in the range of about 5 international units (IU) to about 1000 IU of the chemodenervating agent.
  • a preferred dosage for this purpose is less than 500 IU, and most preferably about 300 IU or less.
  • the dosage preferably is administered as a plurality of injections about the trigger point in the afflicted muscle or muscle group.
  • An international unit is defined as the LD 5Q for a standard 20 gram white mouse. Dosages also can be administered based upon the volume of muscle denervated by a unit quantity of a chemodenervating agent as described in above-referenced patent application USSN 07/570,395.
  • active compound in a specific case will vary according to the agent utilized, the particular compositions formulated and the particular site and patient being treated. Dosages for a given patient can be determined using customary, clinical practices. Botulinum toxin preparations have been used in the past to treat certain spasmodic conditions of muscle. However, these preparations have not been indicated for the management of specific pain syndromes. The present invention demonstrates that chemodenervating agents such as botulinum toxins can be applied for the localized, sustained relief of pain resulting from myofascial pain syndrome.
  • the present method can be used to treat any muscle or muscle group in a patient afflicted with myofascial pain syndrome.
  • Anatomic regions in which myofascial pain syndrome has been described include, but are not limited to, the following muscles with associated restrictions in range of motion and/or referred pain:
  • Lateral pterygoid Refers pain to ears, temporomandibular joint, cheek and jaw
  • Medial pterygoid Refers pain to ears and temporomandibular joint, cheek, jaw, throat and front of neck
  • Multifidi Refers pain to back of neck Occipitalis Refers pain to back of head and eye area
  • Orbicularis oculi Refers pain to eye area, cheek and jaw
  • Temporalis Refers pain to back of head, temporal area, eye area and teeth
  • Zygomaticus major Refers pain to front of head, cheek and jaw
  • the present method can be used to treat post operative myofascial pain.
  • Myofascial pain syndrome is a principal component of post operative complaints.
  • Traditional treatments for post-operative pain include physical therapy and non-steroidal anti-inflammatory medications, which have met with varying degrees of success.
  • the present method is effective in post ⁇ operative relieving myofascial pain syndrome and has the advantage of providing localized refief to the pain source without administering systemic drugs which may induce unwanted side effects.
  • An example of the efficacy of the present method in treating post ⁇ operative myofascial pain is shown in Example 2.
  • E.C. is an otherwise healthy 26 year old woman with a history of chronic pain.
  • the pain has been characterized as a dull ache primarily within the region of the left shoulder that has been radiating up the posterior aspect of her skull and down towards the mid position of the low back.
  • the pain has been very severe and has prevented the patient from maintaining gainful employment for approximately two years. She has undergone extensive evaluation at the Pain Clinic at the University of Massachusetts Hospital, Massachusetts General Hospital and Spaulding Rehabilitation Hospital.
  • the pain was characterized as radiating to the inner aspect of her arm as well as to the region of the left portion of her neck. Although there was no posture abnormality associated with the pain, the patient felt stiffness in her neck movement when trying to make rotation excursions to the right and left. There was no evidence of dystonia or involuntary movement present.
  • Tense bands were palpated within her left trapezius muscle in a region of a consistent trigger point. Some generalized increase in muscle tone was also noted in this region. Pressing on the trigger point produced pain in the same region which the pain was spontaneously present. Pressing on the trigger point also produced pain in the same quality as that experienced by the patient. Extensive neuroradiographic work-up of the cervical spine, cervical dorsal and lumbar spine failed to show any substantial bone or joint pathology.
  • botulinum A toxin Allergan Pharmaceuticals, Inc.
  • the patient underwent a second injection receiving a 5 point injection of botulinum toxin at a total dose of 100 IU over the left trapezius muscle.
  • the patient was able to increase her activity to part-time employment and increase her demands of physical therapy.
  • Her physical therapist noticed a clear improvement in her ability to function and noted that there had been clear progress after the injections.
  • the patient noticed increased strength in her muscles and experienced less headache pain.
  • LF LF is an unfortunate 36 year old woman with a 15 year history of temporomandibular joint disease and chronic pain along the masseter and temporalis muscles. Fifteen years prior to evaluation she noted increased immobility of the jaw associated with pain and jaw opening and closing and tenderness along each side of the face. The left side was originally thought to be worse than the right. She was diagnosed as having temporomandibular joint (TMJ) dysfunction with subluxation of the joint and was treated with surgical orthoplasty meniscusectomy and condyle resection.
  • TMJ temporomandibular joint

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'on traite la douleur associée au syndrome de Costen en administrant à un muscle d'un patient atteint du syndrome une quantité thérapeutiquement efficace d'un agent chimiodénervatif qui bloque sélectivement la libération de l'acétylcholine au niveau des plaques motrices, ce qui provoque la décontraction et l'atrophie du muscle traité. Le traitement produit un effet analgésique prolongé, localisé au niveau du site de la source de la douleur myofasciale.
EP94906673A 1993-01-15 1994-01-13 Procede de traitement du syndrome de costen Withdrawn EP0679090A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US5040 1987-01-20
US504093A 1993-01-15 1993-01-15
PCT/US1994/000626 WO1994015629A1 (fr) 1993-01-15 1994-01-13 Procede de traitement du syndrome de costen

Publications (1)

Publication Number Publication Date
EP0679090A1 true EP0679090A1 (fr) 1995-11-02

Family

ID=21713832

Family Applications (1)

Application Number Title Priority Date Filing Date
EP94906673A Withdrawn EP0679090A1 (fr) 1993-01-15 1994-01-13 Procede de traitement du syndrome de costen

Country Status (5)

Country Link
EP (1) EP0679090A1 (fr)
JP (1) JP4381477B2 (fr)
AU (1) AU6030494A (fr)
CA (1) CA2153781A1 (fr)
WO (1) WO1994015629A1 (fr)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9120306D0 (en) 1991-09-24 1991-11-06 Graham Herbert K Method and compositions for the treatment of cerebral palsy
US6974578B1 (en) 1993-12-28 2005-12-13 Allergan, Inc. Method for treating secretions and glands using botulinum toxin
EP1477183B1 (fr) * 1993-12-28 2005-11-02 Allergan, Inc. Composante neurotoxique de la toxine botulinique pour la modulation des secretions controllées par le système cholinergique
US8557256B2 (en) 1993-12-28 2013-10-15 Allergan, Inc. Treatment for cervical dystonia with the neurotoxic component of a botulinum toxin
US8187612B2 (en) 1993-12-28 2012-05-29 Allergan, Inc. Use of the neurotoxic component of a botulinum toxin for treating a spastic muscle
US5766605A (en) * 1994-04-15 1998-06-16 Mount Sinai School Of Medicine Of The City University Of New York Treatment of autonomic nerve dysfunction with botulinum toxin
EP0758900B1 (fr) * 1994-05-09 2002-04-10 BINDER, William J. Toxine de Botulinum pour la REDUCTION DES CEPHALEES DE LA MIGRAINE
GB9508204D0 (en) 1995-04-21 1995-06-07 Speywood Lab Ltd A novel agent able to modify peripheral afferent function
US5721215A (en) * 1996-03-20 1998-02-24 Allergan Injectable therapy for control of muscle spasms and pain related to muscle spasms
US6113915A (en) * 1999-10-12 2000-09-05 Allergan Sales, Inc. Methods for treating pain
US6464986B1 (en) 2000-04-14 2002-10-15 Allegan Sales, Inc. Method for treating pain by peripheral administration of a neurotoxin
US6565870B1 (en) 2000-04-28 2003-05-20 Allergan, Inc. Methods for treating bone tumors
US6306423B1 (en) 2000-06-02 2001-10-23 Allergan Sales, Inc. Neurotoxin implant
US6903187B1 (en) 2000-07-21 2005-06-07 Allergan, Inc. Leucine-based motif and clostridial neurotoxins
US7491799B2 (en) 2000-07-21 2009-02-17 Allergan, Inc. Modified botulinum neurotoxins
US7691983B2 (en) 2000-07-21 2010-04-06 Allergan, Inc. Chimera botulinum toxin type E
US6423319B1 (en) 2000-10-04 2002-07-23 Allergan Sales, Inc. Methods for treating muscle injuries
US20020086036A1 (en) 2000-12-05 2002-07-04 Allergan Sales, Inc. Methods for treating hyperhidrosis
US7255865B2 (en) 2000-12-05 2007-08-14 Allergan, Inc. Methods of administering botulinum toxin
US7255866B2 (en) 2001-09-17 2007-08-14 Allergan, Inc. Botulinum toxin therapy for fibromyalgia
US6623742B2 (en) 2001-09-17 2003-09-23 Allergan, Inc. Methods for treating fibromyalgia
US20150258183A1 (en) 2006-06-07 2015-09-17 Botulinum Toxin Research Associates, Inc. Botulinum Toxin and the Treatment of Primary Disorders of Mood and Affect

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5053005A (en) * 1989-04-21 1991-10-01 Gary E. Borodic Chemomodulation of curvature of the juvenile spine
US5183462A (en) * 1990-08-21 1993-02-02 Associated Synapse Biologics Controlled administration of chemodenervating pharmaceuticals

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9415629A1 *

Also Published As

Publication number Publication date
AU6030494A (en) 1994-08-15
JP4381477B2 (ja) 2009-12-09
WO1994015629A1 (fr) 1994-07-21
CA2153781A1 (fr) 1994-07-21
JPH08508241A (ja) 1996-09-03

Similar Documents

Publication Publication Date Title
WO1994015629A1 (fr) Procede de traitement du syndrome de costen
US6632433B2 (en) Method for treating cervical dystonia with botulinum toxin type B
EP1757325B1 (fr) Utilisation de la toxine botulinique pour traiter les douleurs myofasciales
Meythaler et al. Prospective assessment of continuous intrathecal infusion of baclofen for spasticity caused by acquired brain injury: a preliminary report
US8187612B2 (en) Use of the neurotoxic component of a botulinum toxin for treating a spastic muscle
WO2003073994A2 (fr) Methodes de traitement de syndromes nerveux compressifs
Ward et al. The management of pain in spasticity
US8557256B2 (en) Treatment for cervical dystonia with the neurotoxic component of a botulinum toxin
Wilk Surgical management of refractory craniomandibular pain using radiofrequency thermolysis: a report of thirty patients
Minciu Cerebral palsy management
Glenn et al. Chemical denervation for the treatment of hypertonia and related motor disorders: phenol and botulinum toxin
DO WEBB et al. Current Concepts in Treating Hemiplegic Shoulder Pain
Morton et al. The role of botulinum toxin in the management of cerebral palsy
AU727737B2 (en) Method for treating dysphagia
Patil et al. Application of Botulinum Toxin in Myofascial Pain Dysfunction Syndrome
AU2005200248B2 (en) Method for treating dystonia with botulinum toxin type B
CA2300703C (fr) Methode pour traiter la sudation excessive
Kanji Convergent referred muscle pain: a case series using a segmental approach for chronic pain without pathology
CA2589987C (fr) Methode pour traiter une secretion cholinergique influencee
Guerri A SYSTEMATIC REVIEW OF OBSERVATIONAL STUDIES OF PATIENTS WITH OCULAR HYPERTENSION OR GLAUCOMA RECEIVING LONG TERM TOPICAL EYE THERAPIES
Center et al. Home/Blog/Where does back pain come from?
AU1636700A (en) Method for treating dystonia with botulinum toxin type B
AU2923402A (en) Method for treating dystonia with botulinum toxin type B

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19950727

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL PT SE

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: INTERACTIVE BIOLOGICS ASSOCIATES

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

17Q First examination report despatched

Effective date: 19971024

18D Application deemed to be withdrawn

Effective date: 19970801