The goal of this clinical trial is to learn about oxytocin ( a naturally occurring hormone made in the brain that transmits messages) and the effects it may have on thermal heat pain after intravenous administration. The main question it aims to define is the time course of change in pain score after a 5 minute heating of the skin administered at intervals during and following infusion of intravenous oxytocin in order to create a Pharmacokinetic and a Pharmacodynamic model for oxytocin-induced analgesia.

Participants will be asked to rate thermal heat temperatures before, during and after the intravenous infusion of oxytocin.

The primary objective is to define the time course of change in pain score after a 5 minute heating of the skin applied at intervals during and following infusion of intravenous oxytocin in order to create a Pharmacokinetic and Pharmacodynamic model for oxytocin-induced analgesia.

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 °Celsius to the lower calf.

Statistical programs in the data analysis will be written in R. The software and anonymized data will be included both as digital supplements in the published papers and will be posted on GitHub under github.com/StevenLShafer. Interested investigators will be able to reproduce the published analyses from these files. Consistent with the posting of software and data to the OpenTCI initiative, the software and de-identified data will be made available with "no strings attached," enabling investigators to freely use the data to inform or supplement additional research without restriction. Data to be made available are oxytocin dose, times of pharmacodynamic measures (relative to the start of dosing), simulated plasma oxytocin concentrations at those times for each subject, and age, weight, and sex for each subject.

Data will become available upon publication or upon posting results in ClinicalTrials.gov, whichever comes first, with no expiration.

These data are freely shared to all and will be posted at the URL below

5 to 7 days after oxytocin infusion

On the day of oxytocin infusion, vital signs were recorded at intervals before and up to 180 minutes after beginning the first infusion. Subjects were observed for transient facial flushing and were queried for any adverse events. On visits 24 hr and 5 to 7 days later, subjects were queried regarding any adverse events.

Analgesic effects from an acute, experimental pain stimulus may not mirror the presence, magnitude and duration of analgesia in clinical settings in the treatment of acute or chronic pain. Additionally, contributions if any, of expectations of efficacy (placebo effect) to pain report were not assessed in this study.