Methods of alleviating neuropathic pain

Abstract

The invention provides a method of alleviating neuropathic pain in a subject by administering a neuropathic pain alleviating amount of prosaposin receptor agonist to the subject. The invention also provides a method of inhibiting the onset of neuropathic pain in a subject by administering neuropathic pain alleviating amount of prosaposin receptor agonist to the subject. The present invention also provides prosaposin receptor agonists and the use of these agonists for stimulating neurite outgrowth, inhibiting neural cell death, promoting myelination and inhibiting neural demyelination. In addition, there is provided a method of inhibiting sensory or motor neuropathy by contacting neuronal cells with a composition comprising an effective inhibiting amount of prosaposin receptor agonist.

We claim:  
     
         1 . A prosaposin receptor agonist having from about 14 to 50 amino acids and comprising the amino acid sequence LIRX 1 NNX 2 TX 3 X 4 X 3 X 1 X 1 , wherein: 
 X 1  is any amino acid;    X 2  is any amino acid, but not L or R;    X 3  is a charged amino acid; and    X 4 , when present, is a charged amino acid.    
     
     
         2 . The prosaposin receptor agonist of  claim 1 , wherein LIRX 1 NNX 2 TX 3 X 4 X 3 X 1 X 1  has the amino acid sequence shown in SEQ ID NO:2.  
     
     
         3 . The prosaposin receptor agonist of  claim 1 , wherein the prosaposin receptor agonist consists of the sequence shown in SEQ ID NO:1 or SEQ ID NO:2.  
     
     
         4 . A pharmaceutical composition comprising the prosaposin receptor agonist of  claim 1  in a pharmaceutically acceptable carrier.  
     
     
         5 . The composition of  claim 4  in a controlled release formulation.  
     
     
         6 . The composition of  claim 4  in a liposomal form.  
     
     
         7 . The composition of  claim 4  in a lyophilized form.  
     
     
         8 . The composition of  claim 4  in a unit dosage form.  
     
     
         9 . A method of alleviating neuropathic pain in a subject, comprising administering a neuropathic pain alleviating amount of a prosaposin receptor agonist to the subject.  
     
     
         10 . The method of  claim 9 , wherein the prosaposin receptor agonist has from about 14 to 50 amino acids and comprises the amino acid sequence LIRX 1 NNX 2 TX 3 X 4 X 3 X 1 X 1 , wherein: 
 X 1  is any amino acid;    X 2  is any amino acid, but not L or R;    X 3  is a charged amino acid; and    X 4 , when present, is a charged amino acid.    
     
     
         11 . The method of  claim 10 , wherein LIRX 1 NNX 2 TX 3 X 4 X 3 X 1 X 1  has the amino acid sequence shown in SEQ ID NO:2.  
     
     
         12 . The method of  claim 10 , wherein the prosaposin receptor agonist is an amino acid sequence selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:2.  
     
     
         13 . The method of  claim 9 , wherein prosaposin receptor agonist is an amino acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO: 5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18 and SEQ ID NO:19.  
     
     
         14 . The method of  claim 9 , wherein the neuropathic pain results from a peripheral nerve disorder.  
     
     
         15 . The method of  claim 14 , wherein the peripheral nerve disorder is selected from the group consisting of neuroma; nerve compression; nerve crush, nerve stretch and incomplete nerve transsection; mononeuropathy and polyneuropathy.  
     
     
         16 . The method of  claim 9 , wherein the neuropathic pain results from a disorder selected from the group consisting of a disorder of dorsal root ganglia, spinal cord, brainstem, thalamus and cortex.  
     
     
         17 . The method of  claim 9 , wherein the administering is selected from the group consisting of intravenous, intramuscular, intradermal, subcutaneous, intracranial, intracerebrospinal, topical, oral, transdermal, transmucosal and transnasal.  
     
     
         18 . A method of inhibiting the onset of neuropathic pain in a subject, comprising administering a neuropathic pain alleviating amount of a prosaposin receptor agonist to the subject.  
     
     
         19 . The method of  claim 18 , wherein the prosaposin receptor agonist has from about 14 to 50 amino acids and comprises the amino acid sequence LIRX 1 NNX 2 TX 3 X 4 X 3 X 1 X 1 , wherein: 
 X 1  is any amino acid;    X 2  is any amino acid, but not L or R;    X 3  is a charged amino acid; and    X 4 , when present, is a charged amino acid.    
     
     
         20 . The method of  claim 19 , wherein LIRX 1 NNX 2 TX 3 X 4 X 3 X 1 X 1  has the amino acid sequence shown in SEQ ID NO:2.  
     
     
         21 . The method of  claim 18 , wherein the prosaposin receptor agonist consists of the amino acid sequence shown in SEQ ID NO:1 or SEQ ID NO:2.  
     
     
         22 . A method of stimulating neurite outgrowth, inhibiting neural cell death, promoting myelination or inhibiting demyelination, comprising: 
 contacting neuronal cells with a composition comprising an effective amount of a prosaposin receptor agonist, wherein the prosaposin receptor agonist has from about 14 and 50 amino acids and comprises the sequence shown in SEQ ID NO:2.    
     
     
         23 . The method of  claim 22 , wherein the composition comprises a peptide having the sequence shown in SEQ ID NO:2.  
     
     
         24 . The method of  claim 22 , wherein the contacting is in vitro.  
     
     
         25 . The method of  claim 22 , wherein the contacting is in vivo.  
     
     
         26 . A method of inhibiting sensory or motor neuropathy, comprising: 
 contacting neuronal cells with a composition comprising an inhibiting effective amount of a prosaposin receptor agonist.    
     
     
         27 . The method of  claim 26 , wherein the prosaposin receptor agonist has from about 14 to 50 amino acids and comprises the amino acid sequence LIRX 1 NNX 2 TX 3 X 4 X 3 X 1 X 1 , wherein: 
 X 1  is any amino acid;    X 2  is any amino acid, but not L or R;    X 3  is a charged amino acid; and    X 4 , when present, is a charged amino acid.    
     
     
         28 . The method of  claim 27 , wherein LIRX 1 NNX 2 TX 3 X 4 X 3 X 1 X 1  has the amino acid sequence shown in SEQ ID NO:2.  
     
     
         29 . The method of  claim 26 , wherein the prosaposin receptor agonist is selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:2.  
     
     
         30 . The method of  claim 26 , wherein the contacting is in vitro.  
     
     
         31 . The method of  claim 26 , wherein the contacting is in vivo.