Methods of treatment of opioid tolerance, physical dependence, pain, and addiction with inhibitors of certain growth factor receptors

Abstract

Methods of preventing the development and reversing or partially reversing opioid tolerance in a subject are provided herein. Such methods include the step of administering to a subject in need thereof a therapeutically effective amount of a PDGFR modulator or EGFR modulator alone or together with an opiate analgesic. The methods can also be used for the treatment of refractory neuropathic pain, physical dependence or addiction.

1 .- 17 . (canceled) 
     
     
         18 . A method of treating μ opioid tolerance in a subject comprising the step of administering to a subject in need thereof a therapeutically effective amount of a PDGFR or EGFR tyrosine kinase small molecule inhibitor to the subject in a pharmaceutical formulation comprising cyclodextrin, cyclodextran, or other cycloamylose. 
     
     
         19 . The method of  claim 18 , wherein the tyrosine kinase inhibitor is imitanib, gefitinib or erlotinib or lapatinib. 
     
     
         20 . The method of  claim 18 , wherein the tyrosine kinase inhibitor is administered to the subject in combination with a μ opioid selected from morphine, fentanyl, codeine, thebaine, diacetylmorphine (heroin), dihydrocodeine, hydrocodone, hydromorphone, nicomorphine, oxycodone, oxymorphone, alphamethylfentanyl, alfentanil, sufentanil, remifentanil, carfentanyl, and ohmefentanyl. 
     
     
         21 . The method of  claim 18 , wherein the tyrosine kinase inhibitor is administered spinally, intravenously, intraperitoneally, intramuscularly, subcutaneously, or orally. 
     
     
         22 . The method of  claim 18 , wherein the formulation comprises a cyclodextrin, and the cyclodextrin is cyclodextrin sulfobutyl ether. 
     
     
         23 . The method of  claim 22 , wherein the cyclodextrin sulfobutyl ether is sulfobutylether-7-b-cyclodextrin.