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Papers of the Week

Papers: 16 Feb 2019 - 22 Feb 2019

Animal Studies


2019 Jan-Dec

Mol Pain


Role of Intraganglionic Transmission in the Trigeminovascular Pathway.


Hurley JH, Kunkler P E, Zhang LJ, Knopp KL, Oxford G S
Mol Pain. 2019 Jan-Dec; 15:1744806919836570.
PMID: 30784351.


Migraine is triggered by poor air quality and odors through unknown mechanisms. Activation of the trigeminovascular pathway by environmental irritants may occur via activation of TRPA1 receptors on nasal trigeminal neurons, but how that results in peripheral and central sensitization is unclear. The anatomy of the trigeminal ganglion suggests that noxious nasal stimuli are not being transduced to the meninges by axon reflex but likely through intraganglionic transmission. Consistent with this concept, we injected CGRP, ATP or glutamate receptor antagonists or a gap junction channel blocker directly and exclusively into the trigeminal ganglion and blocked meningeal blood flow changes in response to acute nasal TRP agonists. Previously, we observed chronic sensitization of the trigeminovascular pathway after acrolein exposure, a known TRPA1 receptor agonist. To explore the mechanism of this sensitization, we utilized laser dissection microscopy to separately harvest nasal and meningeal trigeminal neuron populations in the absence or presence of acrolein exposure. mRNA levels of neurotransmitters important in migraine were then determined by RT-PCR. TRPA1 message levels were significantly increased in meningeal cell populations following acrolein exposure compared to room air exposure. This was specific to TRPA1 message in meningeal cell populations as changes were not observed in either nasal trigeminal cell populations or dorsal root ganglion populations. Taken together, this data suggests an important role for intraganglionic transmission in acute activation of the trigeminovascular pathway. It also supports a role for upregulation of TRPA1 receptors in peripheral sensitization and a possible mechanism for chronification of migraine after environmental irritant exposure.