Generate a Pharmacodynamic Model of Oxytocin for Peripheral Analgesic Effects

This is a study of participants that will receive an intravenous (IV) infusion of oxytocin (naturally occurring hormone that is made in the brain).

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 an IV catheter placed. After placement of the IV catheter oxytocin will be given by IV infusion. Investigators will perform some tests to evaluate how oxytocin changes perceptions on the skin. Investigators will study a painful perception by placing a probe on the skin and heating it to 113 -117 degrees Fahrenheit (F) 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. The 5 minute heating temperature will be determined according to the subjects pain rating during the screening visit.

The main goal of the study is to determine the effect of oxytocin during and after a fixed rate intravenous infusion on reduction in pain to a sustained heat stimulus in order to generate a model for peripheral analgesia.

In this study healthy people or those with knee arthritis so severe that they may need joint replacement are recruited for a one day study. Study participants will come to the Clinical Research Unit (CRU) and one intravenous (IV) catheter will be inserted in the forearm for oxytocin infusion. Participants in this study will receive oxytocin at a steady rate for 30 minutes. This information will be analyzed by another group at Stanford University in the Pharmacokinetic/Pharmacodynamic (PK/PD) Core part of this application. Mathematics will be utilized to calculate how quickly oxytocin moves from the blood to where it reduces pain.

Investigators will also do a pain test to determine how much oxytocin reduces pain. For this Investigators will place a probe on the skin and heat it to 113 - 117 degrees for 5 minutes. Study participants will score any pain they feel 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.

Eligibility Criteria:
Inclusion Criteria:

1. Male or female \> 18 and \< 75 years of age, Body Mass Index (BMI) \<40.
2. Generally in good health as determined by the Principal Investigator based on prior medical history, American Society of Anesthesiologists physical status 1, 2, or 3.
3. For healthy volunteers, normal blood pressure (systolic 90-140 mmHg; diastolic 50-90 mmHg) resting heart rate 45-100 beats per minute) without medication. For knee arthritis subjects, normal blood pressure or, for those with hypertension, pressure controlled with anti-hypertensives and with a resting heart rate 45-100 beats per minute.
4. Female subjects of child-bearing potential and those \< 1 year post-menopausal, must be practicing highly effective methods of birth control such as hormonal methods (e.g., combined oral, implantable, injectable, or transdermal contraceptives), double barrier methods (e.g., condoms, sponge, diaphragm, or vaginal ring plus spermicidal jellies or cream), or total abstinence from heterosexual intercourse for a minimum of 1 full cycle before study drug administration.

Exclusion Criteria:

1. Hypersensitivity, allergy, or significant reaction to any ingredient of Pitocin®
2. Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the Principal Investigator, would place the subject at increased risk (active gynecologic disease in which increased tone would be detrimental e.g., uterine fibroids with ongoing bleeding), compromise the subject's compliance with study procedures, or compromise the quality of the data
3. Women who are pregnant (positive result for serum pregnancy test at screening visit), women who are currently nursing or lactating, women that have been pregnant within 2 years
4. Subjects with neuropathy, chronic pain, diabetes mellitus, or taking benzodiazepines or pain medications on a daily basis.
5. Subjects with current or history of ventricular tachycardia, atrial fibrillation or prolonged QT interval.
6. Subjects with past or current history of hyponatremia or at risk for hyponatremia; anyone taking thiazide diuretics, loop diuretics, combination diuretics, lithium, carbamazepine, enalapril, Ramipril, celecoxib, temazepam, gliclazide, glimepiride, glibenclamide, glipizide, omeprazole, pantoprazole, desmopressin, SSRI's, MAOI, or the recreational drug ecstasy.
7. Subjects with a known latex allergy.
8. Subjects with a pain score rating of 1 or less during the initial training session to a 5 minute heating of 45°C- 47 °C to the lower calf.