US 20100184685A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0184685 A1 Zavala, JR. et al. (43) Pub. Date: Jul. 22, 2010

(54) SYSTEMS AND METHODS FORTREATING Publication Classification POST OPERATIVE, ACUTE, AND CHRONIC (51) Int. Cl. PAIN USING AN INTRA-MUSCULAR A638/16 (2006.01) CATHETERADMINISTRATED A6IP 29/00 (2006.01) COMBINATION OF A LOCAL ANESTHETIC A6M 25/00 (2006.01) AND ANEUROTOXIN (52) U.S. Cl...... 514/12: 604/523 (57) ABSTRACT (76) Inventors: Gerardo Zavala, JR., San Antonio, TX (US); Gerardo Zavala, SR. Systems, and methods for the use of Such systems, are San Antonio, TX (US) described that allow for the administration of a combination of a Sustained release local anesthetic compound (such as bupivicaine) through a catheter based administration device Correspondence Address: and direct visualization or percutaneous injection of a neuro JACKSON WALKER LLP toxic protein compound (such as botulinum ) for post 901 MAIN STREET, SUITE 6000 operative and refractory treated muscle pain and discomfort DALLAS, TX 75202-3797 (US) in patients having undergone spinal Surgery and other muscle splitting or treatments aimed at improving muscle pain. The (21) Appl. No.: 12/689,381 systems utilize specific catheter-based administration proto cols and methods for placement of the catheter in association with muscles Surrounding the spine and other anatomical (22) Filed: Jan. 19, 2010 sites within the patient. The utilization of an initial bolus of a specific combination of medications (local anesthetic com Related U.S. Application Data pound and\or neurotoxic protein compound) followed by a dosage pump administration through the catheter is antici (60) Provisional application No. 61/145,621, filed on Jan. pated. A variety of local anesthetics (in addition to bupivic 19, 2009, provisional application No. 61/257,724, aine) and a number of different (in addi filed on Nov. 3, 2009, provisional application No. tion to the ) may be utilized in the 61/295,960, filed on Jan. 18, 2010. medicament administration protocols described.

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SYSTEMS AND METHODS FOR TREATING especially the Surrounding muscle. Surgical pain and trauma POST OPERATIVE, ACUTE, AND CHRONIC is experienced not only by those muscles directly cut at the PAIN USING AN INTRA-MUSCULAR Surgical site but also indirectly to the Surrounding muscles CATHETERADMINISTRATED that tend to contract and/or stress in an effort to compensate COMBINATION OF A LOCAL ANESTHETIC for those muscles directly weakened by the Surgical proce AND ANEUROTOXIN PROTEIN dure. 0005. Therefore, while local anesthetics and general anal gesics can address pain associated with the post-operative 0001. This application claims priority to U.S. Provisional patient in the acute pain setting (4-6 hours post operative), Patent Application Ser. No. 61/145,621, filed Jan. 19, 2009, they often fail to fully address the ongoing pain that follows entitled SYSTEMS AND METHODS FOR TREATING the 4-6 hours directly post-Surgery, especially Surgery involv POST OPERATIVE, ACUTE, AND CHRONIC PAIN ing the muscles attached to the spine and other muscle split USING AN INTRA-MUSCULAR CATHETERADMINIS ting procedures. Therefore, it becomes necessary to repeat TERED COMBINATION OF ANESTHETIC AND ANEU administration of these pain relievers (local anesthetics and/ ROTOXIN PROTEIN, and U.S. Provisional Patent Applica or systemic analgesics and/or muscle relaxants) for extended tion Ser. No. 61/257,724, filed Nov. 3, 2009, entitled periods of time, and for longer than what might be preferred. SYSTEMS AND METHODS FOR TREATING POSTOP This is necessary because these medications alone fail to ERATIVE, ACUTE, AND CHRONIC PAIN USING AN address one or more of the ongoing causes of post-operative INTRA-MUSCULAR CATHETER ADMINISTERED pain, including that muscle spasm and pain deriving from the COMBINATION OF ANESTHETIC AND A NEURO direct and indirect trauma discussed above. TOXIN PROTEIN, and U.S. Provisional Patent Application 0006 For chronic muscular pain patients, current treat Ser. No. 61/295,960, filed Jan. 18, 2010, entitled DECREAS ments available are comprised of one or a combination of the ING POST OPERATIVE PAIN, the entire content of each is following: over-the-counter (“OtC) medications, prescrip hereby incorporated by reference. tion medication, occupational/physical therapy, massage treatments, and invasive anesthetic delivery treatments to the FIELD OF THE INVENTION epidural space, facet, or intramuscular spaces and other regionally affected areas. Although most patients’ symptoms 0002 The present invention relates generally to methods are improved with these interventions there remains a number for treating muscle pain related to spasm, post operative and of patients that would benefit from the introduction of a other types of muscle pain. The present invention relates more combination of catheter administration of anesthetic with specifically to systems and methods for treating post-opera neurotoxin protein. tive and chronic pain using a subfacial and intra-muscular 0007 Local anesthetics are agents which prevent trans catheter administered local anesthetic and injection of a neu mission of nerve impulses without causing unconsciousness. rotoxin protein. Local anesthetics typically act by binding to fast sodium channels from within (in an open state). Local anesthetics can BACKGROUND be either ester or amide based, or combination aminefester 0003. There is a need for the more effective administration based or natural anesthetics like and . of pain relief medication to two types of patients: 1) those Ester local anesthetics (for example, procaine, amethocaine, who have undergone Surgical and other muscle splitting pro cocaine) are generally unstable in solution but are fast-acting. cedures, especially those involving the spine and Surrounding Unfortunately allergic reactions are common with ester local tissue (i.e. post-operative patients); and 2) those patients who anesthetics. Amide local anesthetics (for example, lidocaine, have been refractory to current conventional treatments to prilocalne, bupivicaine, levobupivacaine, ropivacaine and alleviate muscle pain (i.e. chronic pain Sufferers). At present, dibucaine) are generally heat-stable, with a long shelf life most treatment protocols call for the intermittent, or periodic, (around 2 years). They have a slower onset and longer half administration of local anesthetic compounds to the Surgical life than ester anesthetics. These agents are generally used site or area of pain in order to alleviate pain as it arises in a within regional and epidural or spinal techniques, due to their postoperative or conventionally-treated chronic muscular longer duration of action, which can often provide adequate pain patient. In some cases, systems have been developed for analgesia for Surgery, labor, and symptomatic relief. the administration of a Sustained release of a local anesthetic 0008 Lidocaine (as an example) is a common local anes compound, Such as through the use of a medication infusion thetic and antiarrhythmic drug and is often used topically to catheter. A typical example of such an existing infusion cath relieve itching, burning and pain from skin inflammations, as eter directed toward Supra and Subfacial administration of a well as being injected as a dental anesthetic, and in minor local anesthetic or a narcotic is provided by the ON-QR Surgery. Lidocaine, the first amino amide type local anes Painball infusion catheter system developed and marketed by thetic, was first synthesized in 1943 and was first marketed in I-Flow Corporation of Lake Forest, Calif. (hereinafter, the On 1948. As an anesthesia, lidocaine alters depolarization in Q System). Other efforts attempt to treat post-operative pain neurons by blocking the fast voltage gated sodium (Na) with periodic administrations (injections) of local anesthetic channels in the cell membrane. With sufficient blockade, the compounds and/or the use of local and systemic analgesics. membrane of the presynaptic neuron will not depolarize and 0004. In post-operative patients, the choices of pain relief So fail to transmit an , leading to its anesthetic medications are aimed only at treating the multiple sources of effects. the pain felt by most post-operative patients. This is not 0009 While conventional pain management systems as always effective. The trauma caused by a Surgical procedure described above may benefit from the sustained release of a can result in pain derived directly from the site of intervention local anesthetic, such systems fail to fully and efficiently and from the indirect involvement of the Surrounding tissue, address the pain associated with muscle splitting Surgical US 2010/0184685 A1 Jul. 22, 2010

intervention procedures in a post-operative patient or in those been some more recent use of BTX-A for the treatment of patients who have refractory painto current treatments to help spasticity and muscle pain disorders, with approvals pending alleviate pain. A more complete combination of pain treat in many European countries and studies on headaches (in ment compounds, administered in an effective manner, would cluding migraine), prostatic symptoms, asthma, obesity and serve to more efficiently and effectively address the pain and other indications ongoing. Botox R is manufactured in the discomfort of a patient having undergone Surgical or other U.S. by Allergan, Inc. for both therapeutic as well as cosmetic related invasive procedures, and it would serve as an alterna use. Botulinum Toxin Type B (BTX-B) received FDA tive to current treatments of chronic pain. approval for treatment of cervical dystonia in December 0010 Most muscular pain, in particular refractory treated 2000. Trade names for BTX-B are Myobloc R in the United muscle pain and post-operative pain, is often comprised of States, and NeuroblocR) in the European Union. two or more components, including incisional pain and 0016. There are seven serologically distinct toxin types, muscle spasm. Severe pain can last for greater than 7 days if designated A through G3 subtypes of Ahave been described. proper measures are not taken to address it. Long periods of The toxin is a two-chain polypeptide with a 100-kDa heavy post-operative pain and refractory muscular pain increase chain joined by a disulfide bond to a 50-kDa light chain. This hospitalization, worsen patient outcomes and elevate total light chain is an enzyme (a protease) that attacks one of the medical costs. fusion proteins (SNAP-25, syntaxin or synaptobrevin) at a 0011 Common conventional pain treatments include neuromuscular junction, preventing vesicles from anchoring opioids, non-steroidal anti-inflammatory drugs (NSAIDs), to the membrane to release acetylcholine. By inhibiting ace and muscle relaxants, and multimodal analgesic treatments tylcholine release, the toxin interferes with nerve impulses are considered Superior to monotherapy in improving pain. and causes flaccid (sagging) paralysis of muscles in botulism Preferred routes of delivery for analgesics include intrave as opposite to the spastic paralysis seen in . It was nous, patient-controlled analgesia (PCA) bolus, oral, intra discovered in the 1950s that injecting overactive muscles with muscular, and epidural. minute quantities of botulinum toxin type-A decreased 0012 Conventional post-operative and chronic pain treat muscle activity by blocking the release of acetylcholine at the ments have several disadvantages, impacting the gastrointes neuromuscular junction, thereby rendering the muscle unable tinal (GI) system (constipation, post op illus, nausea, GI to contract for a period of time. bleed), the respiratory system (atelectasis, pneumonia, pull (0017 BOTOX(R) (Botulinum Toxin) is indicated for the monary emboli), neurological system (altered mental status), treatment of cervical dystonia in adults to decrease the sever and cardiovascular system (hypotension, tachycardia, myo ity of abnormal head position and neck pain associated with cardial infarction). In addition, prolonged periods of immo cervical muscular spasms. BOTOXOR) is also indicated for the bility can cause deep venous thrombosis, pneumonia, pain, treatment of severe primary axillary hyperhidrosis that is and spasm. For these reasons, conventional post-operative inadequately managed with topical agents. Finally, treatments can prolong hospital stays and increase healthcare BOTOX(R) is indicated for the treatment of strabismus and COStS. blepharospasm associated with dystonia, including benign 0013. One third of all patients who underwent spinal Sur essential blepharospasm or VII nerve disorders in patients 12 gery experienced severe bouts of nausea and Vomiting post years of age and above. operatively, prolonging hospital stays. Post-operative nausea 0018 BOTOXOR) temporarily stops muscle spasms in a non and vomiting (PONV) can cause electrolyte imbalance, dehy sedating manner. It also has been reported to have secondary dration, general malaise, and can require prolonged physical effects of lessening the sensation of pain. therapy intervention. PONV is worsened by conventional 00.19 U.S. Pat. No. 6,447,787 teaches methods for post-operative treatments such as opioids and muscle relax enhancing would healing. ants. NSAIDs can also cause GI irritation, increase bleeding (0020 U.S. Pat. No. 3,966,934 teaches synergistic local and platelet inhibition, worsen renal failure, and decrease the anesthetic compositions. fusion rate of spinal instrumentation. (0021 U.S. Pat. No. 4,029,793 teaches synergistic local 0014 Subfascial pain catheters are FDA-approved or anesthetic compositions. FDA-cleared devices which can address post-operative pain 0022 United States Patent Publication No. 2008/0292612 through the introduction of subfascial catheters that deliver a teaches a composition containing several botulic . constant infusion of an anesthetic medication into the Sur 0023 United States Patent Publication No. 2007/0264373 rounding post operative paravertebral musculature. Such teaches toxin induced sympathectomy. catheters may be silver impregnated, decreasing infection 0024 United States Patent Publication No. 2009/002890 rates. teaches a process for providing a temperature-stable muscle 0015 There are several types of neurotoxin proteins relaxant on the basis of the neurotoxic component of botuli described in the literature which could be a potential substi num toxin in a Solid form. tute for Botox. Our description will mention Botox but is not 0025 United States Patent Publication No. 2008/0213315 limited to Botox. The Botulinum toxin is a neurotoxin protein teaches clostridial toxin pharmaceutical compositions. produced by the bacterium botulinum. In 0026. United States Patent Publication No. 2008/0021051 December 1989, BTX-A (Botox(R) was approved by the U.S. teaches phytotoxins and uses thereof. Food and Drug Administration (FDA) for the treatment of 0027 United States Patent Publication No. 2007/0026019 Strabismus, blepharospasm, and hemifacial spasm. In April teaches Botulinum toxin compositions. 2002, the FDA announced the approval of botulinum toxin 0028. The present invention seeks to combine the benefi type A (Botox Cosmetic(R) to temporarily improve the cial effects of a local anesthetic compounds (such as appearance of moderate-to-severe frown lines between the lidocaine) administered through a catheter-based device and eyebrows (glabellar lines). BTX-A has also been approved injection of a neurotoxic protein compound (such as Botuli for the treatment of excessive underarm Sweating. There has num toxin) for the treatment of post-operative and chronic US 2010/0184685 A1 Jul. 22, 2010

pain in patients. The invention provides an improved post anesthetic. The molecule which inhibits the release of acetyl operative and chronic pain management strategy, which choline at a neuromuscular junction may be a neurotoxin decreases post-operative and chronic pain, increases patient protein, preferably a Botulinum toxin, preferably BTX-A, mobility, decreases the duration of hospital stays, and BTX-B, BTX-C, BTX-D, BTX-E, BTX-F, BTX-G, most decreases the overall medical costs incurred, improving eco preferably BTX-A or B. In a preferred embodiment, the mol nomic recuperation and improving overall patient satisfac ecule which inhibits release of acetylcholine at a neuromus tion. cular junction may be delivered concurrently with a local anesthetic, preferably lidocaine or bupivicaine, and adminis SUMMARY tered interior to the fascia of a subject. Neurotoxin proteins 0029. The present invention provides for systems, and appropriate for use in the present invention include any toxin methods for the use of such systems, that allow for the admin that acts specifically on nerve cells, especially by interacting istration of a Sustained release of a local anesthetic compound with membrane proteins such as ion channels, including: (such as, but not limited to, lidocaine or bupivicaine) through , , Botulinum toxin, , a catheter-based administration system in combination with , , Domoic acid, Hefutoxin, direct injection of a neurotoxic protein compound (such as Kokoi , , , PhTx3, Saxitoxin, Botulinum toxin) for post-operative and refractory muscular , , , and Tetrodotoxin. pain. The systems utilize specific catheter-based administra 0035. In a preferred embodiment, the invention may com tion protocols and methods for placement of the catheter in prise a molecule which inhibits the release of acetylcholine at association with muscles Surrounding the spine. The utiliza a neuromuscular junction concurrently with a local anes tion of an initial bolus of a specific combination of medica thetic, preferably an ester or amide based local anesthetic. In tions (local anesthetic compound and/or neurotoxic protein a preferred embodiment, the local anesthetic may be compound) followed by a dosage pump administration lidocaine, prilocalne, bupivicaine, levobupivacaine, ropiv through the catheter is anticipated. A variety of local anes acaine, or dibucaine, most preferably lidocaine or bupivic thetics (in addition to lidocaine or bupivicaine) and a number aine. Local anesthetics appropriate for use in the present of different neurotoxin proteins (in addition to the Botulinum invention include esters, for example Benzocaine, Chlorop toxin mentioned above) may be utilized in the medicament rocaine, Cocaine, Cyclomethycaine, Dimethocaine, administration protocols described. It is the combination of Larocaine, Propoxycaine, Procaine, Novocaine, Propara these two interventions that is a novel idea in providing caine, Tetracaine, and Amethocaine; amides, for example improved pain relief in a non-sedating manner as an alterna Articaine, Bupivacaine, Carticaine, Cinchocaine, Dibucaine, tive to current treatments to chronic and post operative pain Etidocaine, Levobupivacaine, Lidocaine, Lignocaine, Mepi treatmentS. vacaine, Piperocaine, Prilocalne, Ropivacaine, Trimecaine; BRIEF DESCRIPTION OF THE DRAWINGS and naturally occurring anesthetics including Saxitoxin, and Tetrodotoxin. 0030 The following drawings form part of the present 0036. The present invention contemplates the use of a specification and are included to further demonstrate certain Botulinum toxin at a dose of between 1 unit and 900 units, aspects of the present invention. The invention may be better administered in a concentration of 0.001 units/kg-30 units/kg. understood by reference to one or more of these drawings in Preferably the Botulinum toxin will be administered at a dose combination with the detailed description of specific embodi of between 10 units and 350 units, administered in a concen ments presented herein. tration of 0.01 units/kg-20 units/kg, most preferably at a dose 0031 FIG. 1 is a partially schematic diagram showing a of 20-200 units, and in a concentration of 1 units/kg-10 units/ system for administering the medicament combination asso kg. ciated with the methods in an embodiment of the present 0037. The present invention contemplates the use of an invention; and amide based local anesthetic at a therapeutically effective 0032 FIG. 2 is a flow chart diagram describing the basic dose, preferably between 0.01% and 8. steps in the method of administration of the compound of the 0038. In a preferred embodiment, the invention may com system in an embodiment of the present invention. prise a method for treating chronic pain. The pain may be in DETAILED DESCRIPTION OF PREFERRED a Subject that has undergone a Surgical or muscle splitting EMBODIMENTS procedure, or the pain may be refractory or chronic pain in a Subject that has undergone one or more treatments for pain, 0033. The present invention relates to systems and meth Such as massage, physical therapy, occupational therapy, or ods for treating pain by delivering a local anesthetic concur pain management treatments including epidural, facet, or rently with a neurotoxin protein. Pain may result from a intramuscular injections. In a preferred embodiment, the Surgical or muscle splitting procedure, or may be refractory to invention may be used to treat chronic pain or use to treat pain conventional treatment as in chronic pain symptoms. In a in a Subject that has undergone Surgery, including neurosur preferred embodiment, the local anesthetic may be lidocaine gery, spinal Surgery, a caesarian section, joint Surgery, or bupivicaine, and the neurotoxin protein may be Botulinum abdominal Surgery, orthopedic Surgery, general Surgery, car toxin. In a preferred embodiment of the invention, the local diothoracic Surgery, obstetric or gynecologic Surgery, plastic anesthetic may be delivered via a catheter system, and the Surgery, podiatric Surgery or any type of muscle splitting neurotoxin protein may be delivered via direct or percutane Surgery. It is contemplated that the present invention may ous injection. provide treatment for pain derived from incisions, bruises, 0034. In a preferred embodiment, the present invention inflammatory responses, general tenderness, and muscle may comprise a molecule which inhibits the release of ace overuse, as well as pain derived from muscle spasm or those tylcholine at a neuromuscular junction combined with a local from chronic or refractory pain. US 2010/0184685 A1 Jul. 22, 2010

0039. In a further preferred embodiment, the present 0046. In a preferred embodiment, the invention comprises invention may comprise a method for treating: acute and administration of a local anesthetic through an infusion cath chronic pain syndromes, muscle strains and sprains, tendon eter, preferably placed such that the anesthetic is delivered and ligament injury, fracture related pain, post operative pain, subfascially. The anesthetic is delivered concurrently with a causalgia/reflex sympathetic dystrophy, radiculopathic pain, neurotoxin protein, which is administered by direct injection. muscle spasms, myofascial pain syndromes, plexopathy pain An exemplary system that may be modified for use in con syndromes (i.e. brachial, Sacral), rheumatologic or immuno junction with the methods of the present invention is available logic diseases, spinal Stenosis, spondylosis, spondylolesthe through I-Flow Corporation under the ON-QR) Painbuster sis, rotator cuff pathology, muscle dystonia, fibromyalgia, Ball R infusion catheter. Although the referenced system is cerebral palsy, hemifacial spasm, rheumatoid pathology, directed to epidural placement of the catheter, the basic com osteoarthritis, neuropathic pain syndromes, musculoskeletal ponents of the system are operable in conjunction with the pain disorders and syndromes, back and neck pain, cauda methods of the present invention. This system can be modi equina syndrome, crush injuries, and other related disorders. fied to provide subfascial or intramuscular delivery. 0040. The present invention may represent: an alternative 0047. An exemplary protocol associated with the to conventional pain treatment regiments; a pain control described system and which is appropriate for the adminis mechanism for post Surgical use including pain secondary to tration of compounds in the present invention may be muscle splitting procedures; a pain management strategy for described as follows. An initial bolus of medications as pain which is refractory to minimally invasive pain manage described below is administered viaan intramuscular catheter ment regiments including percutaneous epidural steroid to the Surgical region of the patient. In a preferred embodi injections, percutaneous facet injections, percutaneous ment, the bolus of medications may be delivered subfascially. muscle injections with lidocaine or other general anesthetic; For example, an effective amount of local anesthetic, prefer and a treatment option for pain which is refractory to conven ably lidocaine or bupivicaine, may be delivered subfascially, tional pain management strategies. and a neurotoxin, preferably Botulinum toxin, may be com 0041. In a preferred embodiment, the neurotoxin protein bined in a normal Saline solution and introduced according to may be administered directly into the muscle, preferably via the method of the present invention. injection. The local anesthetic may be administered continu 0048. A further exemplary protocol associated with the ously, preferably via a catheter which is connected outside the described system and which is appropriate for the adminis skin to a reservoir of the local anesthetic. tration of compounds in the present invention may be 0042. In a preferred embodiment, the invention utilizes an described as follows. An initial bolus of neurotoxin protein is administration system that includes a catheter that is placed injected subfascially into the subject. The subject is then fitted within the patient and is supplied with a local anesthetic from with a catheter that is placed within the subject and is supplied an infusion pump or a drip administration system at a regu with a local anesthetic, preferably from an infusion pump or latable dosage. A neurotoxin protein is concurrently admin a drip administration system at a regulatable dosage. istered by subfascial direct injection. In a preferred embodi 0049. The present invention further contemplates a diag ment, the catheter is placed subfascially or intramuscularly. nostic tool for differentiating between pain resulting from The catheter preferably delivers medication below the fascia. muscle abnormalities and pain resulting from skeletal abnor 0043. The present invention further contemplates both malities, such as osteoarthritis, facet degeneration or other Subfascial administration of a neurotoxin protein, and bony abnormalities. A local anesthetic and a neurotoxin pro Suprafascial administration Such that the neurotoxin can be tein may be administered to a patient experiencing pain. If the indirectly delivered to the subfascial space. The invention pain improves, the pain is Suspected to originate in the includes any mechanism for delivering a neurotoxic protein muscle, and the patient may continue treatment for an appro to the Subfasical space, including Subfasical injection, or priate period of time, preferably approximately 6 months. In other forms of Subfasical administration, and also Suprafas a preferred embodiment, the patient may receive the local cial injection, or other forms of Suprafascial administration anesthetic for a period of approximately 5-7 days after begin which may result in delivery of neurotoxin protein to the ning treatment, and may receive the neurotoxin protein peri Subfasical space. odically for approximately 6 months, preferably every 4 to 6 0044. In another preferred embodiment, the invention uti weeks. If the patient does not improve using the treatment of lizes an administration system which includes a percutaneous the present invention, the pain is suspected to be related to injection of neuroprotein to the subject, preferably below the joint pain, and other appropriate action can be taken more fascia, preferably by a pain management physician, chiro quickly as a result of this diagnosis. Therefore, the present practor, anesthesiologist, neuroSurgeon, general Surgeon, invention may serve as a diagnostic tool for differentiating interventional radiologist, orthopedic Surgeon, or a family patients with a bone abnormality, such as might benefit from practitioner. A Subfacial intramuscular catheter which is con epidural or facet joint injections, or muscular pain, which nected to a reservoir of local anesthetic may then be placed in would benefit from treatment according to the present inven the subject. tion as described by the mechanism of action of Botox. 0045 FIG. 1 shows the intramuscular placement of the 0050. Without wishing to be bound by theory, it is con catheter in an embodiment of the invention, although the templated that the local anesthetic numbs the muscular pain invention contemplates alternate placements of similar cath after subfascial injection or delivery by a catheter. The mol eters depending upon the specific Surgical procedure that was ecule which inhibits the release of acetylcholine at a neuro carried out. In general, the system of the present invention muscular junction may then paralyze the muscle after percu finds optimal utilization in conjunction with post-operative taneous administration or direct intra muscular injection by patients recovering from Surgical procedures, most typically direct visualization. Both medications may be administered those associated with the spine, abdominal, joint, obstetric/ in low doses intramuscularly such that they do not affect the gynecologic or other muscle splitting operations. entire muscle. It is contemplated that the paralytic effect US 2010/0184685 A1 Jul. 22, 2010

causes less spasm of the muscle and therefore lessens the pain operative patients recovering from muscle splitting Surgical a patient or Subject feels related to muscle spasm. Moreover, procedures, most typically those associated with the spine, it is contemplated that the sensation of pain may be lessened abdomen, joint, and ob?gyn and other muscle splitting proce by administration of the molecule which inhibits the release dures. of acetylcholine at a neuromuscular junction, because inhi 0055. The present invention further contemplates admin bition of the release of acetylcholine from the nerve endings istration of a molecule which inhibits the release of acetyl may decrease nerve impulses or transmission. choline at a neuromuscular junction combined with a local 0051. The present invention further contemplates that pain anesthetic via any method which can deliver the combination in a subject may be managed in distinct stages. Within 3 to 5 to the interior of a fascia of a subject. This may include days of beginning treatment, a subject may receive local topical, enteral, or parenteral, delivery, for example epicuta anesthetic via catheter which is fixed within the subject. This causes numbness of the muscle during this time. A neurotoxin neous, intranasal, oral, intravenous, intraarterial, intramuscu protein, preferably Botulinum toxin, may be administered lar, vaginal, intracerebral, intracerebroVentricular, intracar immediately or within the first 5 days of beginning treatment diac, rectal, Subcutaneous, intraosseous infusion, by direct injection. This functions to decrease muscle spasm intradermal, intrathecal, intraperitoneal, intravesical, intrac and the sensation of pain. Second, within 5 days to 6 weeks of avernosal, transdermal, transmucosal, insufflational, Sublin beginning treatment, administration of anesthetic may be gual, buccal, inhalational, intracisternal, epidural, or intrav ceased while the neurotoxin protein continues to exert effects itreal administration. In a preferred embodiment, delivery of decreasing muscle spasm and sensation of pain. It is con may occur via a catheter system placed subfascially or intra templated that decreasing muscle spasm during recovery may muscularly within a Subject. speed recovery by aiding in healing, and caused decreased scar formation. In a preferred embodiment, a Subject may Example 1 recover post-operatively without having muscle spasm for approximately 4-6 weeks. 0056 Botulinum toxin in a dose of 1-2 units/kg is admin 0052. The catheter in the system for use with the present istered subfascially at the site of pain via direct injection to a invention is first secured at the insertion site with an appro Subject experiencing pain. A catheter is placed subfascially at priate dressing to prevent catching or pulling secure tubing the site of pain within the subject and is supplied with bupiv from a lateral position on the back with tape or steristrips. The icaine at a concentration of 0.5%, from an infusion pump at a pump may be externally Supported (as With a convalescing dosage of 2 ml/hr. patient) or may be secured to the patient on a carrying clip. 0057 With wound open, the fascia and paraspinal muscles Such systems allow the patients to sponge bathe while the are identified. The length of catheter needed is estimated. A catheter is in place, although the wound site should not be trocaris placed 2 cm lateral to the midline incision. The trocar Subjected to bathing, showering, or Swimming. Light activity is bent to allow placement of catheters past fascia and into the is recommended for the patient until the catheter is removed. paravertebral muscles. Catheters are placed in the thoracic 0053 FIG. 2 provides the basic method steps associated and lumbar spine (rostral to caudal insertion) or cervical spine with the use and administration of the medication compound (caudal to rostral insertion). Catheters are secured with ster of the present invention. In the initial step, the medication istreps and dermabond or tegaderm. The procedure is compound comprising pharmaceutically effective quantities repeated on the opposite side. of the local anesthetic, Such as lidocaine or bupivicaine, in saline solution is prepared. The second basic step in the pro cess comprises positioning an intramuscular fluid delivery Example 2 catheter in the post-operative patient adjacent to the Surgical site and connecting a metered reservoir of the prepared medi 0.058 A subject undergoes spinal surgery. After the proce cation compound. The third basic step in the established dure is complete, the Surgeon locates the fascia. The Surgeon therapy is the administration of an initial bolus of the local bends the trocar, and inserts the trocar into paraspinal anesthetic to the patient for the immediate treatment of post muscles. The Surgeon threads the catheter, and holds the operative pain. The initial composition and/or rate of admin catheter with non-tooth forceps against the skin. The Surgeon istration may preferably be different for the initial bolus and pulls and peals tips of plastic equally in opposite directions. the Subsequent metered dosage. In a fourth basic step, a 0059 Botulinum toxin in a dose of 1-2 units/kg is admin neurotoxin protein may be delivered, preferably by direct istered subfascially at the site of pain via direct injection to the injection, either before, after, or during administration of the Subject experiencing pain. A catheter is placed subfascially at local anesthetic. Finally, the method of the present invention the site of pain within the subject and is supplied with bupiv comprises the establishment and administration of an ongo icaine at a concentration of 0.5%, from an infusion pump at a ing post-operative therapy which would, in the preferred dosage of 2 ml/hr. embodiment, include a progressive reduction in the dosages of both the local anesthetic and/or the neurotoxin protein. Example 3 0054 The catheter system and combination of a neuro toxin protein administered concurrently with a local anes 0060 A patient with muscle or back pain which does not thetic of the present invention may be used in any area respond to conventional treatment is fitted with a catheter throughout the body where subfascial or intramuscular which administers bupivicaine subfascially. The patient also administration can be accomplished. In a preferred embodi receives an injection of Botulinum toxin subfascially. Bupiv ment, the invention is used in conjunction with a spinal icaine is administered via the catheter at a concentration of Surgical procedure. In general, the system of the present 0.5% for a period of 5-7 days. Botulinum toxin is adminis invention finds optimal utilization in conjunction with post tered via injection at a concentration of 1-2 units/kg at the US 2010/0184685 A1 Jul. 22, 2010

beginning of treatment, and periodically at intervals of trocar needles were aided by shaping of the catheters and by approximately 4-6 weeks for a total treatment time of feeling the catheters midline with my thumb as it progressed approximately 6 months. thru the paraspinal muscles. Visual inspection of each side of the midline incision was done to verify that no part of the Example 4 plastic sheath covering the trocar needles could be seen thru the paraspinal muscle. 0061. A subject experiencing pain is treated with bupivic 0.066 Once the trocar needles were positioned into the aine at a concentration of 0.5% administered through the paraspinal muscles, the trocar needles were removed and the catheter at a rate of 2 ml/hr for a time period of 5 days. The plastic sheath was left in place. Then silver impregnated Subject also receives an injection of botulinum toxin at a infusion catheters were introduced thru the plastic sheath concentration of 1-2 units/kg. The pain improves using this where the trocar needles had been. As the infusion catheters treatment, and bupivicaine treatment is discontinued after 7 reached the end of the plastic sheath, resistance from the days, and the subject receives further injections of botulinum paraspinal muscles prevented the infusion catheter from pro toxin every 6 weeks for a total period of 6 months. gressing any further. Example 5 0067. Holding the infusion catheters against the skin, the plastic sheaths were peeled off the infusion catheters bilater 0062. A subject experiencing pain is treated with bupivic ally. This was accomplished because the plastic sheath has aine at a concentration of 0.5% administered through the two tabs at the portion exposed at the skin which split in two catheter at a rate of 2 ml/hr for a time period of 5 days. The as the plastic sleeve was elevated out, leaving behind only the Subject also receives an injection of botulinum toxin at a infusion catheters. The infusion catheters were then attached concentration of 1-2 units/kg. The pain does not improve, and to a 400 cc reservoir containing Marcaine 0.5% without epi the Subject begins treatment for joint pain. nephrine. 0063 Although the present invention has been described in terms of the foregoing preferred embodiments, this Postoperative Course: description has been provided by way of explanation only and 0068. On post operative day 0, the patient was ambulating is not intended to be construed as a limitation of the invention. the halls of the hospital and participating in occupational and Those skilled in the art will recognize modifications of the physical therapy evaluations. On postoperative day 3, the compounds, systems, and methods of the present invention patient's pain was Sufficiently controlled to be discharged that might accommodate specific Surgical and post-operative home. He rated his pain3-4/10 on the visual analog pain scale requirements with the patient. As indicated above, the specific and did not require any patient controlled analgesic (PCA) local anesthetic and the specific neurotoxin protein may be administration during his hospitalization. varied in their composition ratios and dosages. In addition, the specific manner of administration, including the initial 0069. On post op day #15 the patient was seen for suture administration and the metered administration, may be varied removal without signs of infection of the previous infusion according to the mobility of the patient and the quantities of catheter sites. There were no markings noted were the infu medication required. These modifications do not necessarily sion catheters had been. depart from the spirit and scope of the methodology of the Example 7 present invention. 0070 A 66 year old male was suffering from significant Example 6 progressive low back and radiating leg pain. On further diag nostic work up he was noted to have lumbar levoscoliosis Intraoperative Placement of Infusion Pain Catheters with coronal imbalance and the apex of the imbalance at L4-5. into the Paraspinal Muscles and not into the Lumbar The MRI of the lumbar spine demonstrated significant bilat Fascia eral foramenal compression of the L4-S1, loss of disk height 0064. A 57 year old presented with progressive numbness, and significant disk degeneration of L5-S1. After discussion tingling and weakness of bilateral arms and progressive gait with the patient, a L4-S1 decompressive laminectomies with difficulties. After further investigative studies he was diag bilateral foraminotomies, L5-S1 transforaminal interbody nosed with cervical myelopathy secondary to cervical Steno fusion and coronal correction of his anatomical imbalance sis, cervical spinal cord contusion with radiographic cord with pedicle instrumentation from L3-S1 with posterior lat signal abnormalities. Because most of his compression was eral arthodesis from L3-S1 was proposed. posterior, a C3-7 posterior cervical laminectomy and fusion was done to decompress the spinal cord. Intraoperative Description: Intraoperative Description: 0071. After decompression of the central canal of L4-S1 with bilateral foramenotomies, L5-S1 transforaminal inter 0065. After decompression of the spinal cord, placement body fusion and correction of the coronal imbalance was of both lateral mass screw instrumentation, and the posterior accomplished, the pain catheters were then placed. Placement lateral arthothesis, the pain catheters were placed. Placement of the catheters was done in the following way: From the of the catheters was done in the following way: From the midline incision, two five inch silver impregnated catheters, midline incision, two five inch silver impregnated catheters, which deliver 2 cc/hr of Marcaine 2% without epinephrine which deliver 2 cc/hr of Marcaine 2% without epinephrine were introduce bilaterally 2 cm lateral and inferior of the was introduce bilaterally 2 cm lateral and inferior of the superior end of the wound. Trocar needles covered with a inferior end of the wound. Trocar needle which are covered disposable plastic sheath were fashioned to be introduced into with a disposable plastic sheath were fashioned to be intro the paraspinal lumbar muscles. Direction of the trocar needles duced into the paraspinal cervical muscles. Direction of the were aided by shaping of the catheters and by feeling the US 2010/0184685 A1 Jul. 22, 2010

catheters midline with the Surgeon's thumb as it progressed 0083 United States Patent Publication No. 2008/0021051 thru the paraspinal muscles. Visual inspection of each side of with Wilson listed as the inventor, published Jan. 24, 2008 the midline incision was done to verify that no part of the 0084 United States Patent Publication No. 2007/0026019 plastic sheath covering the trocar needles could be seen thru with Hunt listed as the inventor, published Feb. 1, 2007 the paraspinal muscle. What is claimed: 0072. Once the trocar needles were positioned into the 1. A composition for the treatment of post-operative and paraspinal muscles, the trocar needles were removed and the chronic pain, comprising: plastic sheath was left in place. Then silver impregnated a) a local anesthetic; and infusion catheters were introduced through the plastic sheath b) a neurotoxin. where the trocar needles had been. As the infusion catheters 2. The composition of claim 1, wherein the local anesthetic reached the end of the plastic sheath, resistance from the is lidocaine or bupivicaine. paraspinal muscles prevented the infusion catheter from pro 3. The composition of claim 2, wherein the lidocaine is at gressing any further. a concentration of between 0.01% and 8%. 0073 Holding the infusion catheters against the skin, the 4. The composition of claim 2, wherein the bupivicaine is plastic sheaths were peeled off the infusion catheters bilater at a concentration of between 0.01% and 8%. ally. This was accomplished because the plastic sheath has 5. The composition of claim 1, wherein the neurotoxin is two tabs at the portion exposed at the skin which split in two Botulinum toxin. as the plastic sleeve was elevated out, leaving behind only the 6. A method for treating chronic and post-operative pain, infusion catheters. The infusion catheters were then attached comprising the steps of to a 400 cc reservoir containing Marcaine 0.5% without epi a) administering a neurotoxin protein Subfascially to a nephrine. Subject; and b) administering a local anesthetic Subfascially to a Subject. Post Operative Course: 7. The method of claim 6, wherein administration of the 0074. On post operative day 1 the patient was ambulating neurotoxin protein is via injection. with physical therapy and the PCA was discontinued. On post 8. The method of claim 6, wherein administration of the operative day 3 the patient was accepted to rehab and trans anesthetic is via a catheter. ferred to rehab on post operative day 4. The patient had rated 9. The method of claim 6, wherein either the neurotoxin his pain level at a 5-6/10 on the visual analog pain scale on protein or the local anesthetic are administered indirectly to POD #1 and on the day of discharge rated his pain as 4/10 and the subfascial space and allowed to diffuse into the subfascial well controlled with pain medications. Space. 10. The method of claim 6, wherein administration of the REFERENCES CITED neurotoxin protein is directly or percutaneously into a muscle of the subject. 0075. The following references, to the extent that they 11. The method of claim 6, wherein the local anesthetic is provide exemplary procedural or other details Supplementary lidocaine or bupivicaine. to those set forth herein, are specifically incorporated herein 12. The method of claim 11, wherein the lidocaine is at a by reference. concentration of between 0.01% and 8%. 13. The method of claim 11, wherein the bupivicaine is at U.S. Patent Documents a concentration of between 0.01% and 8%. 0076 U.S. Pat. No. 6,447,787 to Gassneret al., issued Sep. 14. The method of claim 6, wherein the neurotoxin is 10, 2002: Botulinum toxin. 0077 U.S. Pat. No. 3,966,934 to Adams, et al., issued Jun. 15. A kit for the treatment of chronic and post operative 29, 1976: pain, comprising: 0078 U.S. Pat. No. 4,029,793 to Adams, et al., issued Jun. a) a local anesthetic; and 14, 1977; b) a neurotoxin. 0079 United States Patent Publication No. 2008/0292612 16. The kit of claim 15, further comprising a catheter. with Berrutet listed as the inventor, published Nov. 27. 17. The kit of claim 15, wherein the local anesthetic is 2008: lidocaine or bupivicaine. 0080 United States Patent Publication No. 2007/0264373 18. The kit of claim 17, wherein the lidocaine is at a with Carrolletal.listed as the inventors, published Nov. 15, concentration of between 0.01% and 8%. 2007 19. The composition of claim 17, wherein the bupivicaine 0081 United States Patent Publication No. 2009/0028906 is at a concentration of between 0.01% and 8%. with Grein et al. listed as the inventors, published Jan. 29, 20. The composition of claim 15, wherein the neurotoxin is 2009 Botulinum toxin. 0082 United States Patent Publication No. 2008/0213315 with Hunt listed as the inventor, published Sep. 4, 2008