Compositions and methods for controlling pain

Abstract

The present disclosure provides compositions and methods for controlling pain. The present disclosure provides methods for identifying agents that control pain.

1 . A method for controlling pain in an individual, the method comprising introducing into a primary afferent neuron of the individual a nucleic acid comprising a nucleotide sequence encoding an opsin polypeptide that provides for hyperpolarization of the primary afferent neuron in response to light of a wavelength that activates the opsin. 
     
     
         2 . The method of  claim 1 , wherein the primary afferent neuron is a nociceptor. 
     
     
         3 . The method of  claim 1 , wherein the light is delivered transdermally. 
     
     
         4 . The method of  claim 1 , wherein the opsin comprises an amino acid sequence having at least about 75% amino acid sequence identity to one of SEQ ID NOs:1, 3, 4, 6, 15, and 16. 
     
     
         5 . The method of  claim 1 , wherein the pain is neuropathic pain. 
     
     
         6 . The method of  claim 1 , wherein said introducing is via injection into a nerve or via intramuscular injection, or wherein said introducing is via topical, intradermal, intravenous, intrathecal, or intrapleural administration. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 2 , wherein the nociceptor is one that is normally activated by a thermal, mechanical, or chemical stimulus. 
     
     
         9 . The method of  claim 1 , wherein the nucleic acid is a recombinant expression vector. 
     
     
         10 .- 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the nucleotide sequence is operably linked to a promoter that provides for selective expression in a neuron. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 1 , wherein the individual is a mammal. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein activation of the opsin provides for an at least 10% reduction in pain. 
     
     
         18 . A non-human animal model of pain, wherein the non-human animal expresses in a primary afferent neuron of the animal a nucleic acid comprising a nucleotide sequence encoding an opsin polypeptide that provides for depolarization of the nociceptor in response to light of a wavelength that activates the opsin. 
     
     
         19 . The non-human animal model of  claim 18 , wherein the primary afferent neuron is a nociceptor. 
     
     
         20 . The non-human animal model of  claim 18 , wherein the opsin comprises an amino acid sequence having at least about 75% amino acid sequence identity to one of SEQ ID NOs:8-14 and 19-21. 
     
     
         21 . The non-human animal model of  claim 18 , wherein the nucleic acid is a recombinant expression vector. 
     
     
         22 .- 24 . (canceled) 
     
     
         25 . The non-human animal model of  claim 18 , wherein the nucleotide sequence is operably linked to a promoter that provides for selective expression in a neuron. 
     
     
         26 . The non-human animal model of  claim 25 , wherein the promoter is a synapsin-I promoter, a human synuclein 1 promoter, a human Thy1 promoter, or a calcium/calmodulin-dependent kinase II alpha (CAMKIIα) promoter. 
     
     
         27 . The non-human animal model of  claim 18 , wherein the animal is a rat or a mouse. 
     
     
         28 . A method of identifying an agent that reduces pain, the method comprising:
 a) administering a test agent to the non-human animal of  claim 18 ; and   b) determining the effect, if any, of the test agent on pain when the depolarizing light-activated polypeptide is activated with light, wherein a test agent that reduces pain in the non-human animal, compared to the level of pain induced by light activation of the depolarizing light-activated polypeptide in the absence of the test agent, indicates that the test agent is a candidate agent for reducing pain.   
     
     
         29 . A method of identifying an agent that reduces pain, the method comprising:
 a) administering a test agent to the non-human animal of  claim 18 ; and   b) determining the effect, if any, of the test agent on the amount of light required to induce pain following administration of the test agent,   wherein a test agent that increases the amount of light required to induce pain is a candidate agent for reducing pain.