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 SKH1 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 1 project will generate a hairless knockout rat colony to compliment the SKH1 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 2 for screening novel analgesic agents.
The specific aims of this phase 1 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 animals' 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.
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 1 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.