Research Submissions

Intranasal Oxytocin Attenuates Reactive and Ongoing, Chronic Pain in a Model of Mild Traumatic Brain Injury

Anders C. Meidahl MD

Anders C. Meidahl MD

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA, USA

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Andreas Eisenried MD

Andreas Eisenried MD

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA, USA

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Michael Klukinov MD

Michael Klukinov MD

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA, USA

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Longhui Cao MD

Longhui Cao MD

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA, USA

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Alexander Z. Tzabazis MD

Alexander Z. Tzabazis MD

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA, USA

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David C. Yeomans PhD

Corresponding Author

David C. Yeomans PhD

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA, USA

Address all correspondence to D.C. Yeomans, PhD, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, 300 Pasteur Dr, Stanford, CA 94305, USA, email: [email protected]Search for more papers by this author
First published: 21 December 2017
Citations: 20

Conflict of Interest: David C. Yeomans is a founder and shareholder of Trigemina. Mikhail Klukinov and Alexander Tzabazis are shareholders of Trigemina.

Funding: A.M. received funding from the Lundbeck Foundation.

Abstract

Background

Approximately 1.7 million Americans sustain a traumatic brain injury (TBI) each year and chronic pain is a common complication.

Objective

We studied the effects of intranasally administered oxytocin as a potential treatment for chronic pain in an animal model of mild TBI.

Methods

The lateral fluid percussion model of mild TBI was chosen for this purpose and after exposure to mild TBI the rats (n = 12) developed hind paw and facial allodynia compared to sham animals (n = 6). Oxytocin or a vehicle was afterwards administered intranasally and reactive pain was assessed by hind paw and facial von Frey testing. Some animals received the oxytocin receptor antagonist, atosiban, in addition to oxytocin/vehicle treatment (n = 12). The effect of oxytocin on ongoing and spontaneous pain was examined through conditioned place preference testing. To determine whether the effects of intranasal oxytocin could be attributed to delivery via the peripheral blood stream, some TBI animals received an intravenous injection of the same oxytocin dose that was given intranasally. ELISA immunoassays were carried out (n = 6) to measure concentrations of oxytocin in the trigeminal ganglia, pons, spinal cord, and olfactory bulb after intranasal administration and evaluate the most likely route of entry.

Results

These studies confirmed that the fluid percussion model can be used to study post-TBI facial allodynia. Oxytocin attenuated both reactive and spontaneous, ongoing non-reactive pain following mild TBI for at least 3-4 hours after intranasal administration by binding to OT or VA1-receptors most likely by a peri-trigeminal nerve mediated uptake.

Conclusions

Intranasal oxytocin attenuates measures of reactive and non-reactive pain in a model of mild TBI and may represent a novel treatment for chronic pain in TBI patients.