Chronic pain is an ongoing medical condition that results in over $600B annual medical costs in the US. The most effective medications for chronic pain remain opioid-based treatments that have significant side effects and potential for abuse and addiction. Dr. John Pintar, Professor of Neuroscience and Cell Biology at Rutgers Robert Wood Johnson Medical School, leads the only group in the world that uses specific genetic models that they have developed to indicate novel targets for treating chronic pain independent of the opioid system. Considering that over 2,500 youths/day abuse a prescription drug for the first time and 25% of teens are reported to have abused pain-related prescription drugs, Dr. Pintar’s research in identifying new targets to treat pain potentially devoid of other side effects will greatly advance healthcare and reduce risks for addiction.

Dr. Pintar’s molecular and genetic approach is very novel and unique in that it recognizes the importance of genetic strain background in modifying the response to mutations in genes that mediate the opioid response in mice. By breeding these mutant genes onto different strain backgrounds, Dr. Pintar and his team have been able to identify totally unexpected analgesic responses and discovered that there are very few and even potentially only one unknown gene that controls theses unique analgesic responses in each of these strains. Applying this approach to two different mutant genes as well as to an individual strain whose mutation to not feel pain arose independently, Dr. Pintar’s group continues to make strides by locating the region of the chromosome in which the modifying mutations are found, and hopes to identify the precise targets that mediate these analgesic responses. In two to three years, the team expects to identify specific genes for all three projects, with subsequent functional analysis to follow.
   
The three projects include:

• Characterizing novel delta opioid receptor (DOR) agonist targets: Dr. Pintar and his team have discovered that DOR knockout mice surprisingly express DOR-like analgesic activity that is strain-background dependent. They have used genetic analysis of strain crosses to define a chromosome region which underlies this analgesic response and in the next step, Dr. Pintar hopes to design and validate methods to measure the expression levels of genes within this specific chromosome region as well as directly compare the relevant DNA sequences of the two strains to identify the gene controlling analgesia.
• Identifying novel morphine-6-glucronide (M-6-G) targets that are present in mu opioid receptor (MOR-1) knockout mice: Just like in the previous project, this analgesia is remarkably strain-specific. Here, Dr. Pinter and his team want to confirm identity of a chromosome region that appears to be mediating the analgesic effect of the opioid compound, and then use the same general approach as in Project 1 to identify the relevant gene controlling this analgesia.  
• Mapping genes underlying high-basal thermal responses in “no-pain” mice: Dr. Pintar’s group has identified mice that do not feel pain when exposed to high heat, and that these mice can pass this trait onto their offspring. Dr. Pintar hopes to 1.) identify the gene that is responsible for this analgesia, and 2.) understand the mechanisms by which this  gene works, and 3.) determine if the same mechanism can mediate other pain responses like surgical pain or injury pain.