Trigeminal brainstem neurons synthesize estradiol and respond to TMJ stimulation

Method: Preclinical evidence suggests that E2 can act rapidly to alter pain-like behavior.  This study used immunohistochemical (IHC) and microdialysis methods to determine if: 1) E2 is synthesized by trigeminal caudalis (Vc) neurons responsive to TMJ stimulation, 2) sex differences exist for E2 synthesis in Vc, and 3) if TMJ stimulation alters E2 levels in Vc.  For IHC, male and female (n = 4/group) rats were anesthetized with pentobarbital and received intra-TMJ injection of the TRPA1 agonist, mustard oil (MO, 20%), or vehicle.  Brainstem sections were processed for Fos protein (neuronal activity marker), aromatase (E2 biosynthetic enzyme) and E2 receptor (ERa).  Microdialysis samples (30 min) were collected from Vc under isoflurane.  The aromatase inhibitor, Anastrozole (100µM), was delivered via the dialysis probe and topically to the Vc surface.

Result: Cells counts in Vc revealed 20-25% of Fos+ neurons were aromatase+ in males and females after TMJ stimulation.  By contrast, the % of Fos/ERa Vc neurons was greater in females than males (41% vs 21%, p<0.025).  Microdialysis results revealed: 1) similar E2 levels in Vc of intact males and females, 2) gonadectomy reduced E2 in Vc by 20% in males and 40% in females, 3) aromatase inhibition transiently reduced E2 by 40-50%, and 4) E2 levels in Vc increased >50% after intra-TMJ injection of MO.  

Conclusion: E2 is synthesized by Vc neurons that encode noxious sensory signals from the TMJ.  The greater density of ERa in Vc of females than males predicts that locally released E2 has a greater effect on neural activity in females.  The function of E2 synthesis in Vc may be to fine tune synaptic activity in the brain driven by input from trigeminal sensory neurons.