Intranasal (IN) Oxytocin Relieves Pain and Depressive Behavior in a Rodent Model of Mild Traumatic Brain Injury (TBI)

Abstract

Evaluate the efficacy of intranasal oxytocin in relieving pain and associated depressive behavior in a rat model of mild TBI. Pain, anxiety, depression and cognitive impairment after TBI are sources of long-term disability for which there is no effective treatment. Decreases in endogenous oxytocin are associated with chronic pain and headache, and exogenous oxytocin reduces both pain and depressive behavior in animals and humans. This study examined the effects of intranasal oxytocin in pain and depressive behavior following TBI in rats. A standardized, reproducible, lateral fluid percussion rat model was employed using male Sprague-Dawley rats. Sham animals underwent the same procedure as the TBI animals except for the pressure pulse upon the dura. At 48-hour post procedure and establishment of hind paw and facial allodynia, 6 rats received IN oxytocin, 6 received IN vehicle. In 12 other rats, 16 ug oxytocin or vehicle was administered intravenously (IV). An additional 6 rats each received either IN oxytocin plus intraperitoneal (IP) oxytocin receptor antagonist atosiban or oxytocin plus vehicle. Rats were assessed on mechanical allodynia, conditioned place preference, and the forced swim test (FST). Oxytocin concentrations in trigeminal ganglia (TG), pons, spinal cord, and olfactory bulb were measured by ELISA immunoassay. IN oxytocin, but not IV or vehicle, attenuated both reactive and spontaneous pain following mild TBI as well as depressive behavior upon FST. This effect was blocked by atosiban, confirming an effect via oxytocin receptors. Immunoassay demonstrated concentrating of oxytocin primarily in TG. IN oxytocin was effective in relieving pain and associated depressive behavior of TBI in this model and has potential to be a safe and effective treatment for TBI headaches and post-concussion syndrome.