Generation of hairless rat pain models

DESCRIPTION provided by applicant Pain is the most common reason for individuals to seek medical care This epidemic leads to the expenditure of billions of dollars for prescription and over the counter analgesics and alternative therapies Several hundred billion more dollars are spent due to lost productivity as a result of pain In a recent report the Institute of Medicin recommended that research on pain and pain therapies be improved and diversified in order to address this growing problem Velocity Laboratories LLC was established to employ novel state of the art techniques to help researchers rapidly identify new pain treatments In establishing protocols for testing analgesic agents it was recognized that one of the main quality of life issues for pain patients is to decide if a particular activity is worth the pain they will have to endure to perform that activity These decisions are critical to the welfare of the patient and as pain worsens the patients become less capable of caring for themselves The resulting psychological toll of pain compounds the suffering and may lead to thoughts of suicide To model these life decisions made by pain sufferers Velocity Labs utilizes a reward conflict rodent assay in which mice or rats must make decisions about the value of a reward relative to a nociceptive stimulus to their face This operant orofacial nociception assay is automated and high throughput allowing a technician to test hundreds of rodents a day To reduce costs of preparing animals for this assay hairless strains of mice and rats are used Unfortunately the only commercially available hairless rat is a natural knockout of the gene frizzy which imparts a hairless phenotype but also reduces the fecundity of the animals In contrast the SKH mice used by Velocity Labs are a natural knockout of the gene hairless which does not impact reproduction or pup care Rats however are often a more desirable species for nociception studies thus this phase project will generate a hairless knockout rat colony to compliment the SKH mouse colony at Velocity labs These animals are expected to reproduce more reliably than the frizzy knockout animals The knockouts will be produced using transcriptional activator like effector nucleases TALEN These animals will then be used to generate several unique pain models in phase for screening novel analgesic agents The specific aims of this phase project are to create the hairless knockout rats and to establish a colony at Velocity Labs and then to evaluate the animals in the operant orofacial nociception assay thermal hind paw nociception assay and the hind paw von Frey mechanical allodynia assay to verify that the animalsandapos nociceptive systems are functionally normal These hairless knockout animals will provide a valuable platform to address one of the most significant quality of life issues facing pain patients and will aid researchers from around the world in developing therapies to address this issue PUBLIC HEALTH RELEVANCE Pain is the most common reason for individuals to seek medical care This epidemic leads to the expenditure of billions of dollars for prescription and over the counter analgesics and alternative therapies Several hundred billion more dollars are spent due to lost productivity as a result of pain This phase project will generate a hairless knockout rat colony for use in novel pain models to address the most pressing issues that impact the quality of life of pain patients