Understanding Cognition, Oxytocin & Pain in Elders

Osteoarthritis (OA) represents a significant cause of disability worldwide in individuals
aged 65 and older, a rapidly growing segment of our population. The knee is the most commonly
affected joint with pain being the primary symptom, negatively impacting physical, cognitive,
and emotional functioning. Symptomatic knee OA has been traditionally attributed to
peripheral mechanisms, but measures of joint damage only modestly account for the presence or
severity of OA-related pain. The neuropeptide oxytocin (OT) has been recognized as a mediator
of endogenous analgesia in animal and human studies. However, little is known about the
neurobiological mechanisms underlying OT's pain-relieving properties.

This study will test the efficacy and safety of self-administered intranasal OT over 4-weeks
in older individuals with knee osteoarthritis. Relative to placebo (P), daily administration
of intranasal OT diminished self-reported pain, physical and emotional functioning and
changes in brain metabolite concentrations. With strong support from the University of
Florida and the McKnight Brain Institute, this interdisciplinary project, using a
comprehensive multi-methods approach, will be the first to determine the potential benefit of
OT as a novel analgesic therapy for knee OA pain in aging.

Inclusion Criteria:

- knee osteoarthritis

Exclusion Criteria:

- Hypersensitivity to OT or vasopressin,

- history of hyponatremia, syndrome of inappropriate antidiuretic hormone secretion, or
psychogenic polydipsia,

- on vasoconstrictors such as desmopressin, pseudoephedrine, or antidiuretic medication,

- low sodium or osmolality levels,

- excessive smoking,

- excessive drinking,

- muscle pain as a result of systemic disease,

- significant nasal pathology,

- previous or concurrent use of narcotics delivered intranasally (e.g., cocaine),

- gastroparesis.

- Participants will also be excluded if they have concurrent medical or arthritic
conditions that could confound symptomatic knee OA-related outcomes or coexisting
disease that could preclude successful completion of the protocol including:

- systemic rheumatic condition (e.g. rheumatoid arthritis, systemic lupus erythematosus,
fibromyalgia);

- a history of clinically significant surgery to the index knee;

- uncontrolled hypertension (>150/95);

- poorly controlled diabetes (HbA1c>7%);

- neurological disease (e.g., Parkinson's, Multiple Sclerosis);

- cardiovascular or peripheral arterial disease;

- serious psychiatric disorder requiring hospitalization within the past twelve months
or characterized by active suicidal ideation;

- diminished cognitive function that would interfere with completion of study procedures
(i.e., MoCA score < 25)]; and

- large pieces of metal in the body or metal in the face or neck,

- claustrophobia,

- major medical surgery in the past two months,

- history of brain surgery or any serious brain condition like aneurysm, stroke, or
seizures].