Pharamaceutical compositions for treating chronic pain and pain associated with neuropathy

Abstract

The present invention provides methods and compositions for the treatment of neuropathic pain. In certain embodiments, compositions comprising an dextromethorphan (or other N-methyl-D-aspartate receptor antagonist), tramadol, and gabapentin can synergistically act to reduce pain in a human patient. Pharmaceutical compositions may also comprise a capsaicinoid, an esterified capsaicinoid, and/or a tricyclic antidepressant.

1 . A pharmaceutical composition comprising a combination of:
 a) tramadol or a tramadol analog;   b) an NMDA antagonist; and   c) gabapentin or a gabapentin analog.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the NMDA antagonist is dextromethorphan, dextrorphan, ketamine, amantadine, memantine, eliprodil, ifenprodil, phencyclidine, MK-801, dizocilpine, CCP ene, flupirtine, or derivatives or salts thereof. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the NMDA antagonist is dextromethorphan. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the composition comprises tramadol, gabapentin, and dextromethorphan. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the tramadol is present at a dose of from about 20 mg to about 60 mg. 
     
     
         6 . The pharmaceutical composition of  claim 4 , wherein the dextromethorphan is present at a dose of from about 25 mg to about 75 mg. 
     
     
         7 . The pharmaceutical composition of  claim 4 , wherein the gabapentin is present at a dose of from about 20 mg to about 100 mg. 
     
     
         8 . The pharmaceutical composition of  claim 4 , wherein the composition comprises from about 28.5 mg to about 40 mg of tramadol, from about 34 mg to about 51 mg of dextromethorphan, and from about 30 mg to about 90 mg of gabapentin. 
     
     
         9 . The pharmaceutical composition of  claim 4 , wherein the amount of any one of the tramadol, dextromethorphan, or gabapentin would be sub-therapeutic when administered without the other two agents. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is formulated for oral administration, a solution, a sustained release formulation, a suspension or elixir for oral administration, an injectable formulation, comprised in an implantable device, a topical preparation, comprised in a solid state or depot type transdermal delivery device, a suppository, a buccal tablet, or an inhalation formulation. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the pharmaceutical composition is formulated for oral administration as a tablet or encapsulated multiparticulate formulation. 
     
     
         12 - 20 . (canceled) 
     
     
         21 . The pharmaceutical composition of  claim 1 , wherein the composition is a tablet or multiparticulate capsule comprising from about 28.5 mg to about 40 mg of tramadol, from about 34 mg to about 51 mg of dextromethorphan, and from about 30 mg to about 90 mg of gabapentin. 
     
     
         22 . A method of treating pain in an individual, comprising administering to a subject an amount of agents including:
 a) tramadol or a tramadol analog;   b) an NMDA antagonist; and   c) gabapentin or a gabapentin analog;   wherein the combined amount of said agents is effective to treat pain.   
     
     
         23 . The method of  claim 22 , wherein the pain results from fibromyalgia syndrome, diabetic neuropathy syndrome, multiple sclerosis, post-surgery pain, arachnoiditis syndrome, trigeminal neuralgia, post-herpetic neuralgia, a cancer, chemotherapy or a radiation therapy. 
     
     
         24 . The method of  claim 22 , wherein the method comprises administering the agents simultaneously or essentially simultaneously. 
     
     
         25 . The method of  claim 24 , wherein the agents are adminstered in a single formulation. 
     
     
         26 . The method of  claim 22 , wherein the method comprises administering the agents sequentially. 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 1 , wherein the agents are administered orally, intravenously, by means of an implant, parenterally, sub-dermally, sublingually, rectally, topically, or via inhalation. 
     
     
         29 . The method of  claim 28 , wherein the agents are administered orally in a tablet or capsule formulation. 
     
     
         30 . The method of  claim 22 , wherein the subject is a human. 
     
     
         31 - 39 . (canceled)