Oxytocin Receptors on Calvarial Periosteal Innervation: Therapeutic Target for Post-Traumatic Headache?

Area of Science:

• Neuroscience
• Pain Research
• Traumatic Brain Injury

Background:

• Mild traumatic brain injury (mTBI) frequently results in acute and persistent post-traumatic headaches (PTHs), lacking approved treatments.
• Trigeminal sensory nerve activation in the calvarial periosteum (CP) is implicated in migraines and PTHs.
• Trigeminal oxytocin receptors (OTRs) are a potential therapeutic target for PTHs.

Purpose of the Study:

• To investigate OTR expression on trigeminal nerves innervating the periosteum.
• To evaluate the therapeutic potential of targeting periosteal OTRs for PTHs.
• To examine the effects of oxytocin application to the periosteum in a rodent model of PTH.

Main Methods:

• Retrograde tracing and immunohistochemistry identified OTRs and CGRPs in trigeminal ganglion (TG) neurons innervating the CP.
• Chemical inflammatory mediators applied to CP modeled mTBI effects, assessing neuronal activation via immediate-early gene expression.
• OTR expression changes post-mTBI and the efficacy of periosteal oxytocin injections in a mouse model of PTH-induced allodynia were evaluated.

Main Results:

• CP afferents in the TG express both OTRs and CGRPs.
• Periosteal inflammation rapidly activated TG neurons, and mTBI increased OTR expression.
• Periosteal oxytocin administration significantly blocked allodynia in acute and persistent PTH phases, an effect reversible with an OTR antagonist.

Conclusions:

• Periosteal trigeminal afferents play a role in post-TBI craniofacial pain.
• The periosteum is a viable local target for therapeutics like oxytocin in managing PTH.