Enhancement of ERK phosphorylation and photic responses in Vc/C1 neurons of a migraine model

Although it is well known that migraine pain is enhanced by photic stimulation of the eye, the mechanisms underlying this response are not yet understood. Noxious stimulation to the dura is known to activate trigeminal spinal subnucleus caudalis and upper cervical spinal cord (Vc/C1) neurons, causing migraine pain. Intense photic stimulation to the eye is also known to activate certain Vc/C1 neurons, thus increasing migraine pain. In this study, we hypothesized that Vc/C1 neurons receiving noxious dural input would be further activated by intense photic stimulation, resulting in the enhancement of migraine pain. However, mechanisms underlying the interactions between dural and photic sensory information in Vc/C1 neurons is unknown. To evaluate the above hypothesis, we studied phosphorylated extracellular signal-regulated kinase (pERK) -immunoreactive (IR) cells in Vc/C1 in dural mustard oil (DMO)-administrated rats. The change in neuronal excitability of Vc/C1 nociceptive neurons receiving input from the dura in DMO rats was examined and tested if those neurons were modulated by intense flush light stimulation. There were many pERK-IR cells in the lateral portion of Vc/C1 after MO administration to the dura. Flashlight presentation to the eye in DMO rats caused an enhancement of ERK phosphorylation in Vc/C1 neurons and pERK-IR cells were significantly suppressed after intracisternal administration of MEK1 inhibitor PD98059. Dura-light sensitive (DL) neurons were recorded in the lateral portion of Vc/C1 and photic responses of DL neurons were significantly enhanced following dural MO administration. These findings indicate that DL Vc/C1 neurons in DMO rats intensified their responses to intense photic stimulation and that ERK phosphorylation in Vc/C1 neurons receiving noxious dural input increased with intense photic stimulation, suggesting that Vc/C1 nociceptive neurons are involved in the enhancement of dural nociception associated with intense light stimulation.