This is an unblinded, sequential study of subjects; all participants will receive an infusion of oxytocin with blood samples taken thereafter in order to create a formula to describe the concentrations of oxytocin in the blood over time (pharmacokinetics). In this study healthy volunteers and people with knee arthritis so severe that they may need joint replacement are recruited for a one day study. Participants will come to the Clinical Research Unit (CRU) and have two IVs inserted; one in each arm. Participants will get a 10 minute infusion through one of the IVs of oxytocin and blood will be taken several times over the next 120 minutes and the amount of oxytocin measured in the blood samples. This information will be analyzed by another group at Stanford University in the Pharmacokinetics/Pharmacodynamics (PK/PD) Core part of this application. Mathematics will be utilized to fit the amount of oxytocin over time as it disappears from blood to a formula, called pharmacokinetics. The effect of subject age, sex, race, ethnicity and weight on the pharmacokinetics of oxytocin will be tested for, since these things can affect how quickly drugs circulate in the blood and are important to better adjust the dose of drug to the individual.~The main purpose of this study is to sample the blood and calculate the pharmacokinetics of oxytocin. Investigators will also do some tests to get a rough idea of how oxytocin changes perceptions on the skin and how this relates to the amount of oxytocin in the blood at the same time. Two kinds of perceptions will be studied. In the first the study team will study a painful perception by placing a probe on the skin and heating it to 113 degrees F for 5 minutes. Subjects will score any pain felt on a 0 to 10 scale, and most people find that pain rises during the 5 minutes, but remains mild, usually around only 1 or 2 on the 0 to 10 scale. In the second, the study team will study the perception of vibration, like one feels with a tuning fork on the skin. For this the study team will put a controlled vibration device on the arm and start the vibration at such a high frequency (1000 times per second) that it cannot be felt as vibrating. The study team will slow the frequency until the subject first feels vibration, then turn off the machine and record this threshold frequency where the participant first feels it. Investigators do these two tests because they test the response of two kinds of nerve fibers - pain fibers and touch fibers - which oxytocin might affect in different ways. With this information investigators will compare the amount of oxytocin in blood over time to its effects on pain and vibration over time using mathematics.~The research participants will not benefit from this study, but the knowledge investigators get will be important not only to adjust oxytocin dose to individuals, but to study its possible effects on pain in a very standardized way. The sample size chosen is needed to get an accurate estimate for the parameters in the pharmacokinetic model for the population, not just the subjects in this study.
The main purpose of this study is to sample the blood and calculate the pharmacokinetics (PK) of oxytocin.~This is an unblinded, sequential study of subjects, all of whom will receive an intravenous (IV) infusion of oxytocin (naturally occurring hormone that is made in the brain) with blood samples taken thereafter in order to create a formula to describe the concentrations of oxytocin in the blood over time (pharmacokinetics).~In this study healthy volunteers and people with knee arthritis so severe that they may need joint replacement are recruited for a one day study. Each study participant will have 2 IV catheters placed (one in each arm). After placement of the IV catheters and infusion of oxytocin will be given over a 10 minute period. Blood samples will be taken before the infusion begins and several times during and after the infusion. The blood will be drawn through the second IV catheter.~The investigators will also do some tests to get a rough idea of how oxytocin changes perceptions on the skin and how this relates to the amount of oxytocin in the blood at the same time. Two kinds of perceptions will be studied. First, the investigators will study a painful perception by placing a probe on the skin and heating it to 113 degrees Fahrenheit for 5 minutes. Each study participant will score any pain that is experienced on a 0 to 10 scale, and most people find that pain rises during the 5 minutes, but remains mild, usually around only 1 or 2 on the 0 to 10 scale. Secondly, the investigators will study the perception of vibration, like one feels with a tuning fork on the skin. For this the investigators will put a controlled vibration device on the arm and start the vibration at such a high frequency (1000 times per second) that it cannot be felt as vibrating. The investigators will slow the frequency until the study participant first feels vibration, then turn off the machine and record this threshold frequency where it is first felt.