Methods for treatment of headaches by administration of oxytocin

Abstract

The present invention relates to methods for the treatment of headache and headache disorders. The methods comprise administration of an oxytocin peptide for the treatment of primary and secondary headaches or trigeminal neuralgia.

1 . A method for the treatment of headache pain comprising administering to an individual in need thereof an effective dose of an oxytocin peptide.  
   
   
       2 . A method according to  claim 1 , wherein said treatment comprises prevention of headache pain.  
   
   
       3 . A method according to  claim 1 , wherein said treatment comprises alleviation of headache pain.  
   
   
       4 . A method according to  claim 1 , wherein the headache is a primary or secondary type headache.  
   
   
       5 . A method according to  claim 1 , wherein the headache is a vascular type or tension type headache.  
   
   
       6 . A method according to  claim 1 , wherein the headache is selected from the group consisting of a migraine headache, a cluster headache or a tension headache.  
   
   
       7 . A method according to  claim 1 , wherein the headache pain is caused by trigeminal neuralgia.  
   
   
       8 . A method according to  claim 1 , wherein the oxytocin peptide is administered via mucosal administration, wherein mucosal administration comprises intranasal administration, buccal administration, sublingual administration and conjunctival administration.  
   
   
       9 . A method according to  claim 1 , wherein the oxytocin peptide is administered via transdermal administration, wherein transdermal administration comprises administering the agent to the skin.  
   
   
       10 . A method according to  claim 1 , wherein the oxytocin peptide is administered via intradermal or subcutaneous injection.  
   
   
       11 . A method according to  claim 1 , wherein the administration is targeted to the trigeminal nerve system.  
   
   
       12 . A method according to  claim 1 , wherein the oxytocin peptide is administered via intranasal administration.  
   
   
       13 . A method according to  claim 12 , wherein the oxytocin peptide is administered to the lower two thirds of the nasal cavity.  
   
   
       14 . A method according to  claim 1 , wherein the oxytocin peptide is administered via buccal or sublingual administration.  
   
   
       15 . A method according to  claim 1 , wherein the oxytocin peptide is administered via conjunctival administration or via other tissues around the eye.  
   
   
       16 . A method according to  claim 1 , wherein the effective dose is about 4 IU to about 24 IU.  
   
   
       17 . A method according to  claim 1 , wherein the oxytocin peptide is administered as a pharmaceutical composition.  
   
   
       18 . A method according to  claim 17 , wherein the pharmaceutical composition further comprises at least one additional active agent.  
   
   
       19 . A method according to  claim 17 , wherein the pharmaceutical composition further comprises at least two additional active agents.  
   
   
       20 . A method according to  claim 17 , wherein the pharmaceutical composition further comprises an additional active agent selected from the group consisting of non-peptide opioids, opioid and opioid-like peptides and their analogs, NMDA-receptor antagonists, sodium channel blockers, calcium channel blockers, adrenergic antagonists, gabaergic agonists, glycine agonists, cholinergic agonists, adrenergic agonists, such as epinephrine, anticonvulsants, Rho kinase inhibitors, PKC inhibitors, p38-MAP kinase inhibitors, ATP receptor blockers, endothelin receptor blockers, pro-inflammatory cytokine, chemokine, interleukin and tumor necrosis factor blockers, pro-inflammatory cytokines, tricyclic antidepressants, serotonergic antagonists, serotonergic agonists, NSAIDs and COXIBs, acetaminophen; analgesic peptides, toxins, TRP channel agonists and antagonists, cannabanoids, antagonists of pro-nociceptive peptide neurotransmitter receptors CGRP 1  and CGRP 2 , antagonists of pro-nociceptive peptide neurotransmitter receptor NK 1 , antagonists of pro-nociceptive peptide neurotransmitter receptor NK 2 , antagonists of pro-nociceptive peptide neurotransmitter receptor Y 1 - 5 , antagonists of pro-nociceptive peptide neurotransmitter receptors VPAC 2 , VPAC 1  and PAC 1 , antagonists of pro-nociceptive peptide neurotransmitter receptors Gal 1 - 3  or GalR 1 - 3 , agonists or antagonists of vasopressin, corticotropin releasing hormone (CRH), growth hormone releasing hormone (GHRH), luteinizing hormone releasing hormone (LHRH), somatostatin growth hormone release inhibiting hormone, thyrotropin releasing hormone (TRH), glial-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), pancreatic polypeptide, peptide tyrosine-tyrosine, glucogen-like peptide-1 (GLP-1), peptide histidine isoleucine (PHI), pituitary adenylate cyclase activating peptide (PACAP), brain natriuretic peptide, cholecystokinin (CCK), islet amyloid polypeptide (IAPP) or amylin, melanin concentrating hormone (MCH), melanocortins (ACTH, α-MSH and others), neuropeptide FF (F8Fa), neurotensin, parathyroid hormone related protein, calcitonin, Agouti gene-related protein (AGRP), cocaine and amphetamine regulated transcript (CART)/peptide, 5-HT-moduline, hypocretins/orexins, nociceptin/orphanin FQ, ocistatin, prolactin releasing peptide, secretoneurin, urocortin and derivatives and analogues thereof.  
   
   
       21 . A method according to  claim 17 , wherein the pharmaceutical composition further comprises an effective therapeutic amount of diclofenac.  
   
   
       22 . A method according to  claim 17 , wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients, adjuvants, diluents or stabilizers.  
   
   
       23 . A method according to  claim 17 , wherein the pharmaceutical composition is administered as a powder, a gel, a film, an ointment, a liquid, a suspension, a cream or a bioadhesive.  
   
   
       24 . A method according to  claim 17 , wherein the pharmaceutical composition further comprises at least one protease inhibitor or at least one absorption enhancer.  
   
   
       25 . A method according to  claim 17 , wherein the pharmaceutical composition further comprises at least one protease inhibitor and at least one absorption enhancer.  
   
   
       26 . A method for the treatment or prevention of migraine headache pain comprising administering to an individual in need thereof an effective dose of an oxytocin peptide wherein the oxytocin peptide is administered via intranasal administration.  
   
   
       27 . A method for the treatment of cluster headache pain comprising administering to an individual in need thereof an effective dose of an oxytocin peptide wherein the oxytocin peptide is administered via intranasal administration.  
   
   
       28 . A method for the treatment of tension headache pain comprising administering to an individual in need thereof an effective dose of an oxytocin peptide wherein the oxytocin peptide is administered via intranasal administration.  
   
   
       29 . A method for the treatment of trigeminal neuralgia comprising administering to an individual in need thereof an effective dose of an oxytocin peptide wherein the oxytocin peptide is administered via intranasal administration.  
   
   
       30 . A method for the treatment of secondary headache pain comprising administering to an individual in need thereof an effective dose of an oxytocin peptide wherein the oxytocin peptide is administered via intranasal administration.  
   
   
       31 . A method according to  claim 1 , wherein the effective dose is about 0.1 IU to about 150 IU.  
   
   
       32 . A method according to  claim 1 , wherein the effective dose is about 1 IU to about 100 IU.  
   
   
       33 . A method according to  claim 26 , wherein the effective dose is about 0.1 IU to about 150 IU.  
   
   
       34 . A method according to  claim 27 , wherein the effective dose is about 0.1 IU to about 150 IU.  
   
   
       35 . A method according to  claim 28 , wherein the effective dose is about 0.1 IU to about 150 IU.  
   
   
       36 . A method according to  claim 29 , wherein the effective dose is about 0.1 IU to about 150 IU.  
   
   
       37 . A method according to  claim 30 , wherein the effective dose is about 0.1 IU to about 150 IU.  
   
   
       38 . A method according to  claim 1 , wherein administration results in reduction of a pain rating on the VAS of 30% or more.  
   
   
       39 . A kit comprising an oxytocin peptide and instructions for treatment of headaches and headache disorders.  
   
   
       40 . A kit according to  claim 39 , further comprising at least one additional analgesic agent.  
   
   
       41 . A kit according to  claim 39 , further comprising a vasoconstrictor.  
   
   
       42 . A kit according to  claim 39 , further comprising at least one protease inhibitor or at least one absorption enhancer.  
   
   
       43 . A kit according to  claim 39 , further comprising at least one protease inhibitor and at least one absorption enhancer.  
   
   
       44 . A kit according to claims  39 , further comprising a delivery device.