Intranasal and Intravenous Oxytocin for Analgesia to Noxious Heat Pain

This protocol will utilize a randomized, triple-masked, cross-over study design to compare intravenous (IV) to intranasal (IN) oxytocin administration for analgesia to an experimental pain stimulus in healthy volunteers. Equal numbers of adult men and women; ages 18-55 will be recruited. Participants will report to the research unit for three visits, 1) screening, informed consent, pregnancy test, and training to consistently rate pain from an FDA-approved device to test heat pain. The lowest temperature which causes a pain score of greater than 2 with 5 minutes of heating will be identified, 2) intravenous infusion and self-administered intranasal spray of study drug and 5-minute heat testing at intervals for 4 hours, 3) a repeat of the procedures done at visit two.

Participants will receive intravenous oxytocin, 20 IU and intranasal placebo on one of these visits and intravenous placebo and intranasal oxytocin, 48 IU, on the other. Pain score at the end of 5-minute skin heating will be compared using mathematical modeling of the time course of change in each individual and in the study population as a whole. The effect, if any, on these models of participant age, sex, and weight will be explored.

Inclusion criteria

• Male or female > 18 and ≤75 years of age, Body Mass Index (BMI) <40.
• Generally in good health as determined by the Principal Investigator based on prior medical history, and as assessed to be American Society of Anesthesiologists physical status 1, 2, or 3.

Exclusion criteria

• Recent (<3 months) nasal surgery or chronic conditions requiring daily intranasal (IN) medications
• Hypersensitivity to any ingredient in Pitocin® (marketed preparation of oxytocin for parenteral injection)
• Latex allergy
• Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the Principal Investigator, would place the subject at increased risk (e.g., active gynecologic disease in which increased tone would be detrimental such as uterine fibroids with ongoing bleeding)
• Women who are pregnant, are currently nursing or lactating, or have been pregnant within 2 years
• Neuropathy, chronic pain (located in any body location that is being treated), diabetes mellitus, or taking benzodiazepines or pain medications on a daily basis.
• Current or history of ventricular tachycardia, atrial fibrillation or prolonged QT interval.
• 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, serotonin selective reuptake inhibitors (SSRI's), monamine oxidase inhibitors (MAOI), or the recreational drug ecstasy.