Methods for treating pain

Abstract

Methods of treating pain by delivery of anti-inflammatory cytokines, proinflammatory cytokine antagonists, and agents that act to reduce or prevent proinflammatory cytokine actions, to the nervous system are described. These agents can be delivered using gene therapy techniques. Alternatively, the agents can be delivered in protein compositions.

1 . A method of treating pain in a vertebrate subject comprising administering to the nervous system of said subject a recombinant vector comprising a polynucleotide encoding an agent selected from the group consisting of an anti-inflammatory cytokine, a proinflammatory cytokine antagonist, and an agent that acts to reduce or prevent inflammatory cytokine actions, operably linked to expression control elements, under conditions that result in expression of said polynucleotide in vivo to reduce pain.  
     
     
         2 . The method of  claim 1 , wherein the subject is administered a polynucleotide encoding an anti-inflammatory cytokine.  
     
     
         3 . The method of  claim 1 , wherein said agent is selected from the group consisting of interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1ra), interleukin-4 (IL-4), interleukin-13 (IL-13), tumor necrosis factor soluble receptor (TNFsr), alpha-MSH, and transforming growth factor-beta 1 (TGF-β1).  
     
     
         4 . The method of  claim 2 , wherein said anti-inflammatory cytokine is IL-10.  
     
     
         5 . The method of  claim 4 , wherein the IL-10 is fused to the Fc portion of an IgG.  
     
     
         6 . The method of  claim 2 , wherein said vertebrate subject is a human and said anti-inflammatory cytokine is human IL-10.  
     
     
         7 . The method of  claim 1 , wherein said recombinant vector is a recombinant virus.  
     
     
         8 . The method of  claim 7 , wherein said recombinant virus is a recombinant adenovirus.  
     
     
         9 . The method of  claim 7 , wherein said recombinant virus is a recombinant adeno-associated virion.  
     
     
         10 . The method of  claim 1 , wherein said recombinant vector is plasmid DNA.  
     
     
         11 . The method of  claim 1 , wherein said administering is by intraparenchymal delivery.  
     
     
         12 . The method of  claim 1 , wherein said administering is by intrathecal delivery.  
     
     
         13 . The method of  claim 1 , wherein said administering is by epidural delivery.  
     
     
         14 . The method of  claim 1 , wherein the pain is neuropathic pain.  
     
     
         15 . A method of treating pain in a mammalian subject comprising intrathecally administering to the central nervous system of said subject a recombinant virus or plasmid comprising a polynucleotide encoding IL-10, operably linked to expression control elements, under conditions that result in expression of said polynucleotide in vivo to reduce pain.  
     
     
         16 . The method of  claim 15 , wherein the IL-10 is fused to the Fc portion of an IgG.  
     
     
         17 . The method of  claim 15 , wherein said vertebrate subject is a human and said IL-10 is human IL-10.  
     
     
         18 . The method of  claim 15 , wherein said subject is administered a recombinant virus.  
     
     
         19 . The method of  claim 18 , wherein said recombinant virus is a recombinant adenovirus.  
     
     
         20 . The method of  claim 18 , wherein said recombinant virus and is a recombinant adeno-associated virion.  
     
     
         21 . The method of  claim 1 , wherein said agent is a fragment of IL-10 comprising the sequence of SEQ ID NO:4.  
     
     
         22 . The method of  claim 21 , wherein said agent consists of the sequence of SEQ ID NO:4.  
     
     
         23 . The method of  claim 15 , wherein said agent is a fragment of IL-10 comprising the sequence of SEQ ID NO:4.  
     
     
         24 . The method of  claim 23 , wherein said agent consists of the sequence of SEQ ID NO:4.