Administration of capsaicinoids

Abstract

Disclosed in certain embodiments is a method for relieving pain at a site in a human or animal in need thereof, comprising administering by injection or infiltration, a dose of a capsaicinoid and coadministering a vasodilator.

What is claimed is:  
     
         1 . A method for relieving pain at a site in a human or animal in need thereof, comprising: 
 administering at a discrete painful site in a human or animal in need thereof a single injectable or implantable dose of a capsaicinoid in an amount effective to denervate said discrete site without eliciting an effect outside the discrete location and to attenuate pain emanating from said site, said effective dose being from about 1 μg to about 5000 μg of capsaicin or a therapeutically equivalent dose of a capsaicinoid other than capsaicin; and coadministering an amount of a vasodilator.    
     
     
         2 . The method of  claim 1 , wherein the non-anesthetic vasodilator is in the same formulation as the capsaicinoid.  
     
     
         3 . The method of  claim 1 , wherein the vasodilator is in a different formulation than the capsaicinoid.  
     
     
         4 . The method of  claim 1 , wherein the vasodilator is administered by a different route than the capsaicinoid.  
     
     
         5 . The method of  claim 1 , wherein the vasodilator is administered by the same route as the capsaicinoid.  
     
     
         6 . The method of  claim 1 , wherein the vasodilator is administered orally, via implant, parenterally, sublingually, rectally, topically, or via inhalation.  
     
     
         7 . The method of  claim 3 , wherein the administration of the capsaicinoid and the coadministration of the vasodilator have overlapping durations of effect.  
     
     
         8 . The method of  claim 1 , wherein the vasodilator is a nitrate vasodilator.  
     
     
         9 . The method of  claim 1 , wherein the vasodilator is selected from the group consisting of clonitrate, erythrityl tetranitrate, isobutyl nitrate, isoidide dinitrite or mononitrite, isomannide dinitrite or mononitrite, isosorbide dinitrate or mononitrate, mononitrate, mannitol hexanitrate, nitroglycerin, pentaeryhtritol tetranitrate, pentaeryhtritol trinitrate or dinitrite or mononitrite, pentrinitrol, propatyl nitrate, sodium nitroprusside, trolnitrate phosphate, 1,3-propane dinitrite, 1,7-heptane dinitrite, cyclohexylmethyl nitrite, 2-phenylethyl nitrite, 3-chloro-2,2 dimethylpropyl nitrite, tert-amyl nitrite, 2-methyl-2-hexyl nitrite, hexyl nitrite, 2-methyl-1,3-propane dinitrite, 2,2,dimethyl-1,3-propane dinitrite, 2-methyl-2-propyl-1,3-propane dinitrite, 3-hexyl nitrite, octyl nitrite, 4-methyl-2-pentyl nitrite, 4-methyl-1-pentyl nitrite, 2-heptyl nitrite, 3-octyl nitrite, 2-methyl-2-pentyl nitrite, 5-methyl-2-hexyl nitrite, 6-methyl-2-heptyl nitrite pharmaceutically acceptable salts thereof and mixtures thereof.  
     
     
         10 . The method of  claim 8 , wherein the vasodilator is administered orally.  
     
     
         11 . The method of  claim 8 , wherein the vasodilator is administered parenterally.  
     
     
         12 . The method of  claim 1 , wherein the vasodilator is in an effective amount to diffuse the capsaicinoid throughout the desired site of action.  
     
     
         13 . The method of  claim 1 , further comprising administering a local anesthetic to the human or animal.  
     
     
         14 . The method of  claim 13 , wherein the local anesthetic is administered at a site distal to the administration of the capsaicinoid to provide a regional blockade.  
     
     
         15 . The method of  claim 14 , further comprising administering a vasoconstrictor with the local anesthetic to prolong the duration of effect of the local anesthetic.  
     
     
         16 . The method of  claim 1 , wherein said dose of capsaicinoid is administered in a pharmaceutically acceptable vehicle for injection or implantation.  
     
     
         17 . The method of  claim 16 , wherein said pharmaceutically acceptable vehicle is an aqueous vehicle is selected from the group consisting of Sodium Chloride Injection, Ringers Injection, Isotonic Dextrose Injection, Sterile Water Injection, Dextrose, Lactated Ringers Injection and any combinations or mixtures thereof.  
     
     
         18 . An injectable or implantable pharmaceutical composition for attenuating pain at a site in a human or animal in need thereof, comprising from 1 μg to 5000 μg of a capsaicinoid, an effective amount of a vasodilator to diffuse the capsaicinoid throughout the desired site of action, and a pharmaceutically acceptable vehicle for injection or implantation.  
     
     
         19 . The composition of  claim 18 , wherein the vasodilator is a nitrate vasodilator.  
     
     
         20 . The composition of  claim 18 , wherein the vasodilator is selected from the group consisting of clonitrate, erythrityl tetranitrate, isobutyl nitrate, isoidide dinitrite or mononitrite, isomannide dinitrite or mononitrite, isosorbide dinitrate or mononitrate, mononitrate, mannitol hexanitrate, nitroglycerin, pentaeryhtritol tetranitrate, pentaeryhtritol trinitrate or dinitrite or mononitrite, pentrinitrol, propatyl nitrate, sodium nitroprusside, trolnitrate phosphate, 1,3-propane dinitrite, 1,7-heptane dinitrite, cyclohexylmethyl nitrite, 2-phenylethyl nitrite, 3-chloro-2,2 dimethylpropyl nitrite, tert-amyl nitrite, 2-methyl-2-hexyl nitrite, hexyl nitrite, 2-methyl-1,3-propane dinitrite, 2,2,dimethyl-1,3-propane dinitrite, 2-methyl-2-propyl-1,3-propane dinitrite, 3-hexyl nitrite, octyl nitrite, 4-methyl-2-pentyl nitrite, 4-methyl-1-pentyl nitrite, 2-heptyl nitrite, 3-octyl nitrite, 2-methyl-2-pentyl nitrite, 5-methyl-2-hexyl nitrite, 6-methyl-2-heptyl nitrite pharmaceutically acceptable salts thereof and mixtures thereof.  
     
     
         21 . A method for relieving pain at a site in a human or animal in need thereof, comprising: 
 administering at a discrete painful site in a human or animal in need thereof a single injectable or implantable dose of a capsaicinoid in an amount effective to denervate said discrete site without eliciting an effect outside the discrete location, said effective dose being from about 1 μg to about 5000 μg of capsaicin or a therapeutically equivalent dose of a capsaicinoid other than capsaicin; and coadministering an amount of a vasodilator.    
     
     
         22 . The method of  claim 21 , wherein the non-anesthetic vasodilator is in the same formulation as the capsaicinoid.  
     
     
         23 . The method of  claim 21 , wherein the vasodilator is in a different formulation than the capsaicinoid.  
     
     
         24 . The method of  claim 21 , wherein the vasodilator is administered by a different route than the capsaicinoid.  
     
     
         25 . The method of  claim 21 , wherein the vasodilator is administered by the same route as the capsaicinoid.  
     
     
         26 . The method of  claim 21 , wherein the vasodilator is administered orally, via implant, parenterally, sublingually, rectally, topically, or via inhalation.  
     
     
         27 . The method of  claim 23 , wherein the administration of the capsaicinoid and the coadministration of the vasodilator have overlapping durations of effect.  
     
     
         28 . The method of  claim 21 , wherein the vasodilator is a nitrate vasodilator.  
     
     
         29 . The method of  claim 21 , wherein the vasodilator is selected from the group consisting of clonitrate, erythrityl tetranitrate, isobutyl nitrate, isoidide dinitrite or mononitrite, isomannide dinitrite or mononitrite, isosorbide dinitrate or mononitrate, mononitrate, mannitol hexanitrate, nitroglycerin, pentaeryhtritol tetranitrate, pentaeryhtritol trinitrate or dinitrite or mononitrite, pentrinitrol, propatyl nitrate, sodium nitroprusside, trolnitrate phosphate, 1,3-propane dinitrite, 1,7-heptane dinitrite, cyclohexylmethyl nitrite, 2-phenylethyl nitrite, 3-chloro-2,2 dimethylpropyl nitrite, tert-amyl nitrite, 2-methyl-2-hexyl nitrite, hexyl nitrite, 2-methyl-1,3-propane dinitrite, 2,2,dimethyl-1,3-propane dinitrite, 2-methyl-2-propyl-1,3-propane dinitrite, 3-hexyl nitrite, octyl nitrite, 4-methyl-2-pentyl nitrite, 4-methyl-1-pentyl nitrite, 2-heptyl nitrite, 3-octyl nitrite, 2-methyl-2-pentyl nitrite, 5-methyl-2-hexyl nitrite, 6-methyl-2-heptyl nitrite pharmaceutically acceptable salts thereof and mixtures thereof.  
     
     
         30 . The method of  claim 28 , wherein the vasodilator is administered orally.  
     
     
         31 . The method of  claim 28 , wherein the vasodilator is administered parenterally.  
     
     
         32 . The method of  claim 21 , wherein the vasodilator is in an effective amount to diffuse the capsaicinoid throughout the desired site of action.  
     
     
         33 . The method of  claim 21 , further comprising administering a local anesthetic to the human or animal.  
     
     
         34 . The method of  claim 33 , wherein the local anesthetic is administered at a site distal to the administration of the capsaicinoid to provide a regional blockade.  
     
     
         35 . The method of  claim 34 , further comprising administering a vasoconstrictor with the local anesthetic to prolong the duration of effect of the local anesthetic.  
     
     
         36 . The method of  claim 21 , wherein said dose of capsaicinoid is administered in a pharmaceutically acceptable vehicle for injection or implantation.  
     
     
         37 . The method of  claim 36 , wherein said pharmaceutically acceptable vehicle is an aqueous vehicle is selected from the group consisting of Sodium Chloride Injection, Ringers Injection, Isotonic Dextrose Injection, Sterile Water Injection, Dextrose, Lactated Ringers Injection and any combinations or mixtures thereof.  
     
     
         38 . An pharmaceutical composition for attenuating pain at a surgical site in a human or animal in need thereof, comprising a capsaicinoid selected from the group consisting of from 1 μg to 15,000 μg of capsaicin, a therapeutically equivalent amount of one or more other capsaicinoids, and therapeutically equivalent combinations thereof; an effective amount of a vasodilator to diffuse the capsaicinoid throughout the desired site of action; and from about 1 ml to about 100 ml of a pharmaceutically acceptable vehicle for infiltration.  
     
     
         39 . The composition of  claim 38 , wherein the vasodilator is a nitrate vasodilator.  
     
     
         40 . The composition of  claim 38 , wherein the vasodilator is selected from the group consisting of clonitrate, erythrityl tetranitrate, isobutyl nitrate, isoidide dinitrite or mononitrite, isomannide dinitrite or mononitrite, isosorbide dinitrate or mononitrate, mononitrate, mannitol hexanitrate, nitroglycerin, pentaeryhtritol tetranitrate, pentaeryhtritol trinitrate or dinitrite or mononitrite, pentrinitrol, propatyl nitrate, sodium nitroprusside, trolnitrate phosphate, 1,3-propane dinitrite, 1,7-heptane dinitrite, cyclohexylmethyl nitrite, 2-phenylethyl nitrite, 3-chloro-2,2 dimethylpropyl nitrite, tert-amyl nitrite, 2-methyl-2-hexyl nitrite, hexyl nitrite, 2-methyl-1,3-propane dinitrite, 2,2,dimethyl-1,3-propane dinitrite, 2-methyl-2-propyl-1,3-propane dinitrite, 3-hexyl nitrite, octyl nitrite, 4-methyl-2-pentyl nitrite, 4-methyl-1-pentyl nitrite, 2-heptyl nitrite, 3-octyl nitrite, 2-methyl-2-pentyl nitrite, 5-methyl-2-hexyl nitrite, 6-methyl-2-heptyl nitrite pharmaceutically acceptable salts thereof and mixtures thereof.