Abstract: The invention provides agents useful for treating pain. An exemplary agent comprises or consists of the a portion of a retroviral Tat protein. One such agent is the peptide Tat-NR2B9c. This peptide has previously been described as an agent for inhibiting damaging effects of stroke and similar conditions via inhibition of PSD95 interactions with NMDA receptors and/or NOS. The present application provides data showing that the Tat-NR2B9c peptides is effective in alleviation of pain. The alleviation of pain can be obtained at a dose of the peptide below the dose required to inhibit PSD-95 interactions with NMDAR or NOS.

Abstract: The present invention provides agents for inhibiting binding of a pro-neurotrophin to a Vps1 Op-domain receptor, in particular the binding of a pro-NGF or a pro-BDNF to a Sortilin receptor. The invention thus provides agents for the manufacture of a medicament, for treating and/or preventing disease or disorders such as but not limited to neurological, neuropsychiatric and ocular diseases, disorders, and degeneration as well as obesity, diabetes, pain and/or nociception in an individual.

Abstract: Disclosed is a drug effective in the treatment of fibromyalgia. Basically, the disclosed therapeutic agent was created on the basis of experiments showing improvement in symptoms when etanercept was administered to patients suffering from fibromyalgia. Etanercept is known as a therapeutic agent for rheumatoid arthritis, and the JFIQ score of patients not suffering from fibromyalgia improved considerably in the preferred embodiment. In other words, a therapeutic agent for fibromyalgia is disclosed that contains etanercept as an active ingredient in an effective amount.

Abstract: The invention relates to cyclic peptide agonists that bind to the mu (morphine) opioid receptor and their use in the treatment of acute and/or chronic pain. Embodiments of the invention are directed to cyclic pentapeptide and hexapeptide analogs of endomorphin that have (i) a carboxy-terminal extension with an amidated hydrophilic amino acid and (ii) a substitution in amino acid position 2. These peptide analogs exhibit decreased tolerance relative to morphine, increased solubility compared to similar tetrapeptide analogs, while maintaining favorable or improved therapeutic ratios of analgesia to side effects.

Abstract: TRPV1 antagonists and associated methods are provided. A TRPV1 channel antagonist can have the structure: Formula (I) wherein R1 can be —CH3, —(CH2)X(CH)YCH3 where x+y=1-20, an aromatic, a (CH2)n aromatic where n can be less than or equal to 6, a lipid, or a linker, and wherein R2 can be either Formula (II) or Formula (III) Additionally, R3 can be —O—R4 or —NH—R4 and R4 can be —H, —CH3, an ester, a cyclic ester, or an amide.

Abstract: The present invention is directed to a method of producing analgesia in a mammalian subject. The method includes administering to the subject an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl 1, buprenorphine, and sufentanil, or its pharmaceutically acceptable salts thereof, wherein the ?-conopeptide retains its potency and is physically and chemically compatible with the analgesic compound. A preferred route of administration is intrathecal administration, particularly continuous intrathecal infusion. The present invention is also directed to a pharmaceutical formulation comprising an omega conopeptide, preferably ziconotide, an antioxidant, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil.

Abstract: The present invention provides a method for inhibiting NF-?B activity in a subject, the method comprising providing an agent capable of inducing expression of annexin 1, whereby said agent induces expression of annexin 1 and whereby said induced expression of annexin 1 inhibits NF-?B activity. Also provided are annexin 1 mimetics capable of binding to NF-?B and pharmaceutical compositions of such inducing and mimetic agents.

Abstract: The present invention provides methods for treating sinus-evoked headaches using botulinum toxin injected or applied in multiple subcutaneous locations over divisions of the trigeminal nerve in soft tissues and dermatomes overlying the corresponding effected sinuses implicated in the etiology of the pain.

Abstract: The invention provides novel potent inhibitors of the ternary protein complex of nNOS, PSD-95, and the NMDA receptor and pharmaceutical compositions comprising the inhibitors for prophylaxis and/or treatment of excitotoxic-related disease and chronic pain conditions in a subject. The inhibitors are dimeric PSD-95 inhibitors comprising a first peptide or peptide analogue linked to a second peptide or peptide analogue by a linker, wherein the first and the second peptide or peptide analogue comprise at least four amide-bonded residues having a sequence YTXV or YSXV, wherein a. Y is selected from among E, Q, and A, or an analogue thereof, and b. X is selected from among A, Q, D, N,N-Me-A, N-Me-Q, N-Me-D, and N-Me-N or an analogue thereof, and wherein a Cell Penetrating Peptide (CPP) is linked to the linker or to an amino acid side chain of the first and second peptide or peptide analogue. The linker can be a PEG or NPEG linker.

Abstract: Disclosed here is the rational design and use of potent and specific GPCR antagonist pepducins based on GPCR regions such as the third intracellular loop and adjacent regions.

Abstract: The present invention provides improved formulations of botulinum toxin that increase delivery of the botulinum toxin to neural and associated tissues and exhibit a higher specific neurotoxicity and higher potency (in LD50 Units) than available formulations of botulinum toxins. These improved formulations enable physicians to treat a wide variety of pathological conditions with a lower toxin load that reduces the risk of inducing an immune response against the toxin and its associated proteins that may ultimately lead to the development of toxin resistance. These benefits are particularly important in the treatment of conditions that require high-dose or chronic administration of botulinum toxin. Additionally, the decreased in LD50 Unit doses of inventive formulations allows for controlled administration limits diffusion. The present invention also provides methods of treating neuromuscular diseases and pain, using low-dose botulinum toxin.

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7 and/or Nav1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract: In order to provide a composition for treating, improving, or preventing pain, it has been found out that a metallothionein protein is expressed in a normal peripheral nerve, and that the expression is not observed in a peripheral nerve producing pain. Moreover, it has been found out that administering metallothionein to rats having neuropathic pain suppresses the pain in the rats.

Abstract: Botulinum toxin, among other presynaptic neurotoxins is used for the treatment and prevention of migraine and other headaches associated with vascular disorders. Presynaptic neurotoxins are delivered focally, targeting the sphenopalatine ganglion. Exemplary delivery is carried out by way of injection.

Abstract: Disclosed is a pharmaceutical composition for preventing or treating TRPV1 activity-related or inflammation-related, diseases or conditions, containing a Maillard peptide separated from well-aged traditional soy sauce as an active ingredient. The Maillard peptide in the present invention functions both as a TRPV1 agonist and a TRPV1 antagonist, and further functions as a TRPV1 activity modulator. Therefore, the Maillard peptide can be used for preventing or treating TRPV1 activity-related diseases such as pain, neurological diseases, urgent defecation, inflammatory bowel disease, respiratory diseases, urinary incontinence, overactive bladder, neurogenic / allergic / inflammatory skin diseases, skin, eye or mucosal irritation, hyperacusis, tinnitus, vestibular hypersensitivity, heart disease, etc.

Abstract: The present invention is directed to a method of producing analgesia in a mammalian subject. The method includes administering to the subject an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil, or its pharmaceutically acceptable salts thereof, wherein the ?-conopeptide retains its potency and is physically and chemically compatible with the analgesic compound. A preferred route of administration is intrathecal administration, particularly continuous intrathecal infusion. The present invention is also directed to a pharmaceutical formulation comprising an omega conopeptide, preferably ziconotide, an antioxidant, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil.

Abstract: Therapeutic peptides having guanylyl cyclase C agonist activity are disclosed. The therapeutic peptides are analogues of the E. coli STa peptide with non-natural amino acid, isosteric or D-amino acid substituents. The therapeutic peptides are useful in the treatment of chronic ideopathic constipation, inflammatory bowel disease, and other diseases. Pharmaceutical compositions comprising comprising the therapeutic peptides are also disclosed.

Abstract: The following class of molecule is disclosed: a dimer containing a first neublastin polypeptide and a second neublastin polypeptide, wherein: (a) at least one of the polypeptides is glycosylated; (b) at least one of the polypeptides is conjugated at its N-terminus to a water-soluble synthetic polymer; and (c) neither of the polypeptides is conjugated to a water-soluble synthetic polymer at a position other than the N-terminus. Such dimers possess the biological activity of wild-type neublastin while displaying enhanced serum half-life and enhanced potency relative to wild-type neublastin.

Abstract: Methods are disclosed for treating osteoarthritis in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-human NGF antibody, or antigen-binding fragment thereof, wherein at least one symptom associated with osteoarthritis is prevented, ameliorated or improved.

Abstract: Provided is a modified human tumor necrosis factor receptor-1 polypeptide or a fragment thereof that binds to a tumor necrosis factor in vivo or ex vivo. The modified human tumor necrosis factor receptor-1 polypeptide or fragment exhibits improved ability to bind tumor necrosis factor and resistance to proteases.

Abstract: A method for treating a patient with migraine headache includes administering to the patient a therapeutically effective amount of an invertebrate presynaptic neurotoxin in a pharmaceutically safe form. The administration includes extramuscular injection of the neurotoxin to emerging nerve points including foraminal sites for enabling neurotoxin access to concentrated nerve bundles at exit points of the foramina.

Abstract: A human antibody or antigen-binding fragment of an antibody which specifically binds human nerve growth factor (NGF) with KD of 5 pM or less, as measured by surface plasmon resonance, wherein the antibody or fragment thereof binds human NGF with an affinity of about 2-10-fold higher than the antibody or fragment binds rat and mouse NGF. The antibodies are useful in treating pain, including inflammatory pain, post-operative incision pain, neuropathic pain, fracture pain, osteoporotic fracture pain, post-herpetic neuralgia, osteoarthritis, rheumatoid arthritis, cancer pain, pain resulting from burns, gout joint pain, as well as diseases, such as hepatocellular carcinoma, breast cancer, and liver cirrhosis.

Abstract: The present invention relates to compounds which inhibit or antagonize the binding of methylglyoxal (MG) and/or other reactive carbonyl species (RCS) to an arginine- or lysine- containing protein, preferably an arginine- or lysine-containing cellular protein, such as a sodium ion channel, e.g. the sodium ion channel Na(v)1.8. Preferred scavenger compounds are peptides comprising several or multiple repeats of the amino acid sequence motif Gly-Glu-X-Pro (GEXP), wherein X is Arg or Lys, and pharmaceutical compositions thereof. The present invention furthermore relates to the use of the compounds as scavenger or antagonists of methylglyoxal and/or related reactive carbonyl species (RCS). The present invention furthermore relates to the use of the compounds for the prevention and/or treatment of pain, hyperalgesia and pain related diseases, in particular pain and/or hyperalgesia caused by or associated with methylglyoxal and/or reactive carbonyl species (RCS).

Abstract: Botulinum toxin, among other presynaptic neurotoxins is used for the treatment and prevention of migraine and other headaches associated with vascular disorders. Presynaptic neurotoxins are delivered focally, targeting the nerve endings of the trigeminal nerve, the occipital nerve and the intranasal terminals of the parasympathetic fibers originating in the Sphenopalatine ganglion. The administration preferably targets the extracranial nerve endings of the trigeminal nerve in the temporal area, the extracranial occipital nerve endings in the occipital area, and the intranasal terminals of the trigeminal nerve and parasympathetic fibers originating in the Sphenopalatine ganglion. The delivery is carried out by way of injection or topically.

Abstract: A method and solution for perioperatively inhibiting a variety of pain and inflammation processes during arthroscopic procedures. The solution preferably includes a vasoconstrictor that exhibits alpha-adrenergic activity and one or more additional pain and inflammation inhibitory agents at dilute concentration in a physiologic carrier, such as saline or lactated Ringer's solution. The solution is applied by continuous irrigation of a wound during a surgical procedure for peripheral vasoconstriction and inhibition of pain and/or inflammation while avoiding undesirable side effects associated with systemic application of larger doses of the agents.

Abstract: The use of flagellin and flagellin related polypeptides for reducing cancer treatment side effects in mammals is described.

Abstract: The present invention relates to compounds of Formula (I) and their pharmaceutically acceptable salts, wherein the substituents are as described herein, and their use in medicine, in particular as opioid agonists.

Abstract: The present invention is directed to the use of compounds of the formula: for treating pain, in particular neuropathic pain, bipolar disease and migraine headaches.

Abstract: The present invention relates to Huwentoxin-IV variants, polynucleotides encoding them, and methods of making and using the foregoing.

Abstract: The present invention relates to the use of Meteorin for the treatment of allodynia, hyperalgesia, spontaneous pain and phantom pain. In a preferred embodiment the disorder to be treated is allodynia, and hyperalgesia, more preferably allodynia including thermal and tactile allodynia.

Abstract: The disclosure herein relates to modified ?PKC inhibitory peptides, methods of generating such peptides, and method for using ?PKC inhibitory peptides for the treatment of pain.

Abstract: The invention provides for methods and compositions for treatment of pain via craniofacial mucosal administration of an analgesic compound (e.g. a non-opioid analgesic peptide, an NOP agonist or N/OFQ). Intranasal administration of certain analgesic peptides such as N/OFQ results in global analgesic effects.

Abstract: A method for treating a patient who has a neutralizing antibody to a type A1 botulinum toxin. The method includes administering 150 kDa type A neurotoxin from type A2 Clostridium botulinum (A2 NTX) to the patient. In accordance with the present invention, a problem can be solved of decrease in clinical response caused by a neutralizing antibody to a type A1 botulinum toxin produced when a patient is treated with a pharmaceutical preparation containing a type A1 botulinum toxin.

Abstract: Disclosed are compositions and methods related to improving pharmacological properties of bioactive compounds targeting nervous system.

Abstract: The present invention is directed to the use of a class of peptide compounds for treating tumor pain, in particular bone cancer pain, for treating chemotherapy-induced pain and for treating nucleoside-induced pain.

Abstract: A method for treating a patient with migraine headache includes administering to the patient a therapeutically effective amount of an invertebrate presynaptic neurotoxin in a pharmaceutically safe form. The administration includes extramuscular injection of the neurotoxin to emerging nerve points including foraminal sites for enabling neurotoxin access to concentrated nerve bundles at exit points of the foramina.

Abstract: Botulinum toxin, among other presynaptic neurotoxins is used for the treatment and prevention of migraine and other headaches associated with vascular disorders. Presynaptic neurotoxins are delivered focally, targeting the sphenopalatine ganglion. Exemplary delivery is carried out by way of injection.

Abstract: The present invention relates to a method of delivering local anesthetic after dental extraction surgery. The present invention relates to packing the tooth socket with a tinned release local anesthetic which is coordinated with an initial local anesthetic and which lasts up to 5 days. The socket can be surgically sealed or the implant can act as the sealing means.

Abstract: The present invention is directed to a method of producing analgesia in a mammalian subject. The method includes administering to the subject an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil, or its pharmaceutically acceptable salts thereof, wherein the ?-conopeptide retains its potency and is physically and chemically compatible with the analgesic compound. A preferred route of administration is intrathecal administration, particularly continuous intrathecal infusion. The present invention is also directed to a pharmaceutical formulation comprising an omega conopeptide, preferably ziconotide, an antioxidant, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil.

Abstract: The present invention provides an active peptide purified from scorpions, and derivatives, analogues and active fragment which are produced by using genetic engineering technology. The analgesic active peptide VGG is extracted, separated and purified from scorpion, and its amino acid sequence is shown as below: VKDGYIADDRNCPYFCGRNAYCDGECKKNRAESGYCQWASKYGNACWCY KLPDDARIMKPGRCNGG. The present invention further provides a use of the peptides in preparation of an analgesic drug, where the peptide is mixed with a pharmaceutically acceptable carrier to prepare into forms for injection, oral administration, transdermal absorption, and transmucosal absorption.

Abstract: This invention relates in one aspect to non-natural desamino alkyl amino acid compounds, methods of making these compounds, and peptides containing these compounds. In one embodiment, the peptide is neurotensin (8-13) in which the N-terminus is an alpha-desamino, alpha-methyl-N,N-dimethyl-homolysine residue of the invention.

Abstract: The present invention is directed to a method of producing analgesia in a mammalian subject. The method includes administering to the subject an omega conopeptide, preferably ziconotide, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil, or its pharmaceutically acceptable salts thereof, wherein the ?-conopeptide retains its potency and is physically and chemically compatible with the analgesic compound. A preferred route of administration is intrathecal administration, particularly continuous intrathecal infusion. The present invention is also directed to a pharmaceutical formulation comprising an omega conopeptide, preferably ziconotide, an antioxidant, in combination with an analgesic selected from the group consisting of morphine, bupivacaine, clonidine, hydromorphone, baclofen, fentanyl, buprenorphine, and sufentanil.

Abstract: Methods of inducing antinociception in a human are described. The method includes the step of administering an effective dose of a polypeptide comprising L-neo-tryptophan to the human extracranially. The polypeptide containing L-neo-tryptophan could be, but is not limited to, NT64L, NT65L, NT66L, NT67L, NT69L, NT69L?, NT71, NT72, NT73, NT74, NT75, NT76, or NT77.

Abstract: A method for managing withdrawal from an addictive substance is described. The method involves administering one or more peptides having specific activity for the ? and/or ? isozyme of protein kinase C (PKC). The peptide(s) can be administered prior to, concurrent with, or subsequent to administration of the addictive substance. Also described is a kit having at least one container containing a peptide having isozyme-specific activity for ?PKC or ?PKC and instructions for use.

Abstract: In some aspects, the present invention provides methods of treating a subject in need of treatment for neuropathic pain, the method comprising administering a compstatin analog to the subject. In some embodiments, the compstatin analog is administered parenterally, e.g., intravenously.

Abstract: The present invention relates to novel isolated peptides which induce analgesia and which inhibit ASIC channels (Acid Sensing Ion Channels), to the polynucleotides encoding said peptides, and also to the pharmaceutical compositions, host cells and vectors comprising same. In particular, said peptides are isolated from the venom of the snake Dendroaspis polylepis. The present invention also relates to the use thereof as a diagnostic tool or as medicament, and in particular as an analgesic, or for identifying analgesic molecules or molecules which inhibit ASIC channels.

Abstract: There is disclosed an isolated nucleic acid molecule encoding a human neurotrophic growth factor designated enovin and having the amino acid sequence illustrated in FIG. 1, 21, 23 or 24 or encoding a functional equivalent, derivative or bioprecursor of said growth factor. The growth factor preferably comprises the amino acid sequence from position 27 to 139 of the sequence illustrated in FIG. 1, or a functional equivalent, derivative or bioprecursor thereof. The nucleic acid molecule encoding enovin can be used to transform a host cell, tissue or organism by including it in an appropriate vector. The host cell, tissue or organism and the vector also form part of the invention.

Abstract: The disclosure herein relates to modified ?PKC inhibitory peptides, methods of generating such peptides, and method for using ?PKC inhibitory peptides for the treatment of pain.

Abstract: The invention provides pharmaceutical compositions and methods of use thereof for preventing or ameliorating disorders of the nervous system. More specifically, the invention provides pharmaceutical compositions, including phosphopeptides, that when administered disrupt TrkB-mediated activation of PLC?1 phosphorylation. The invention further provides method of treatment comprising administering inhibitors of TrkB-mediated activation of PLC?1 phosphorylation alone or in combination with other pharmaceutical compositions to prevent or ameliorate nervous system disorders such as epilepsy, stroke, anxiety, migraine, and pain.

Abstract: The application provides data from a clinical trial of a PSD-95 inhibitor in subjects undergoing endovascular repair of an aneurysm in or otherwise affecting the CNS. The subjects were stratified by whether the aneurysm ruptured before performing the endovascular surgery. Rupture is associated with higher mortality or increased debilitation if a subject survives. The trial provided evidence of significant benefit in subjects with and without aneurysm rupture before endovascular was surgery performed. Surprisingly, the subjects benefiting most from treatment as judged both by pathology and neurocognitive outcome were those in which the aneurysm had ruptured causing a subarachnoid hemorrhage. These data constitute evidence that a PSD-95 inhibitor is beneficial not only in ischemic and hemorrhagic stroke but in forms of hemorrhage in or affecting the CNS, particularly, subarachnoid hemorrhage.