Prolonged Analgesia in Rodents

DESCRIPTION (provided by applicant): Laboratory animals are often subjected to various painful surgical procedures as well as non-surgical procedures. It is the ethical obligation of all research personnel involved with the care and use of laboratory animals to reduce or preferably eliminate pain and distress by using analgesics, provided these analgesics do not interfere with the research objectives. Furthermore, the Institutional Animal Care and Use Committee (IACUC) must assure that appropriate anesthetics and/or analgesics are used to minimize or eliminate pain and distress for animals undergoing painful procedures. The most widely used laboratory animals for various types of research involving painful procedures are rodents. A survey of current literature indicates that buprenorphine is the most widely used narcotic analgesic for rodents because of its excellent analgesic activity and long duration of action. Moreover, unlike morphine, respiratory depression is not usually a problem with this opioid. However, to provide adequate analgesia, repeated parenteral administration is required for buprenorphine, a process that is inherently stressful to the animals. In order to reduce the frequency of handling and in turn, improve the well being of the animals under treatment, we propose to develop a long-acting formulation of buprenorphine that is capable of maintaining analgesia in mice and rats for 3 to 5 days following a single subcutaneous administration of the formulation. This long acting formulation will be a solution of buprenorphine base in an appropriate pharmaceutically acceptable, injectable, water-miscible solvents/vehicles. Upon subcutaneous injection, the buprenorphine base will precipitate at the injection site because of its poor aqueous solubility when the water-miscible solvent/vehicle in the buprenorphine solution is absorbed at the injection site or is carried away by the aqueous body fluid. The underlying hypothesis of our research is that a long acting formulation of buprenorphine will be able to maintain analgesia in rodents for a prolonged period of time (3-5 days) following a single subcutaneous injection. Such a formulation will not only significantly improve the well being of animals by reducing the dosing frequency and stress to the animals, but also save considerable time for veterinarians and their staff treating the animals. If this formulation is successful, it could be used for other laboratory animals such as rabbits, hamsters, guinea pigs, cats, dogs, pigs and non-human primates with appropriate dose adjustment. The novel long acting formulation of buprenorphine will be able to maintain analgesia in rodents for at least 3 days following a single subcutaneous injection. Such a formulation will improve the well-being of animals by reducing the dosing frequency and stress to the animals, and save considerable time for veterinarians and their staff treating the animals. If this formulation is successful, it could be used for other laboratory animals with appropriate dose adjustment.