Background and purposes: Photophobia is characteristic and important sign of the migraine headache. Recently, we found that the response of dura-sensitive neuron to photic stimulation was enhanced after dura inflammation. Some previous papers also have reported that neurons located in the dorsal horn of the C2 spinal cord (C2 neurons) receive photic inputs suggesting that C2 neurons somehow involved in photophobia.
However, how the C2 neurons are involved in photophobia associated with migraine is unknown. Therefore, the change in neuronal excitability of C2 nociceptive neurons was analyzed in rat model with dural inflammation.
Methods: The Sprague-Dawley rats were anesthetized with pentobarbital sodium (50 mg/kg, i.p.) and the small hole was made in the frontal bone, and 10% mustard oil (MO) was applied to the dura surface around the transverse sinus (migraine rat). Photic stimulation was applied to the eye in migraine and vehicle-treated rats, and c-Fos like immunoreactive (LI) cells and pERK-immunoreactive (IR) cells in C2 were precisely analyzed. To identify trigeminal ganglion (TG) neurons innervating the retina, the fluorogold (FG) solution (4% in distilled water, 10 µl) was injected to the retina using a 31-gauge needle. Substance P (SP), calcitonin generelated peptide (CGRP), TRPV1 immunoreactivities were also detected in the ratina.
Results: Following MO application to the dura, a large number of c-Fos-LI cells was expressed in the transition zone between subnuclei interpolaris and caudalis (Vi/Vc) zone bilaterally and was also in the ipsilateral C2. Photic stimulation to the eye in migraine rat caused an expression of pERK-IR cells in C2, and many of them also showed c-Fos immunoreactivity. FG-labeled trigeminal ganglion cells were observed in the first branch-innervated area of the TG following FG injection into the retina. Many SP, CGRP and TRPV1 immunoreactivities were detected in nerve fibers in the retina.
The present findings suggested that C2 neurons are involved in photophobia associated with migraine, and also suggested that the unmyelinated trigeminal afferents innervating the retina might be one of the sources of photic information in photophobia.
