Noseda and colleagues found that even in patients in whom rod and cone damage in the retina resulted in loss of image migraine pain was worsened by light even in blind patients in whom rod and cone damage had caused loss of image formation.[63] These studies indicated that there are alternative pathways for transmitting a nociceptive response to light. They then used tract-tracing

techniques in animals MG-132 nmr to demonstrate a direct pathway from retinal ganglion cells (primary transducers of non-imaging forming photoregulation) to a region of the posterior thalamus that also responds to stimulation of the dura.[63] They propose this as a pathway for modulation of migraine pain by light. The identification of a novel retinothalamic mechanism highlights the existence of non-trigeminal

pathways for modulation of migraine pain. Inputs via these pathways to regions of the brain involved in migraine may not only exacerbate headache but conversely have the potential to be exploited for therapeutic purposes. Other studies indicate that photophobia is also associated with hyperexcitability of pathways involved in image formation. Denuelle and colleagues used H215O PET to study photophobia in migraineurs during spontaneous migraine attacks, after treatment with sumatriptan, and between attacks.[64] They found that a low intensity of light activated the visual cortex during migraine attacks and after resolution of headache with selleckchem sumatriptan treatment but not during the attack-free interval. They concluded from these observations that visual cortical excitability can occur independently of trigeminal nociception and suggested that this excitability is driven by brainstem nuclei. Studies by Burstein and colleagues examined changes in brain activity associated with mechanical and thermal allodynia (the perception of ordinarily innocuous stimuli as uncomfortable).[65] They used functional MRI blood oxygenation this website level-dependent signals to show that during a migraine attack in which patients had allodynia extending beyond the head, mechanical or thermal stimulation of the hand produced greater posterior

thalamic responses than those evoked by the same stimulation between attacks. These studies implicate sensitization of the thalamus as an important mediator of the sensory sensitivity associated with migraine. Photophobia, phonophobia, and allodynia are generally considered to be symptoms of central sensitization, which refers to increased activity of brain or spinal cord sensory processing pathways that lead to increased or altered sensory perception. In traditional pain models, this occurs as a secondary consequence of peripheral nociceptive input. The early occurrence of sensory sensitivity (particularly photophobia and phonophobia) during a migraine attack and the imaging evidence that these phenomena can be independent of trigeminal input are not consistent with this model.