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When activated, the trigeminal nerve causes the eye pain associated with cluster headaches. The trigeminal nerve also stimulates another group of nerves that causes the eye tearing and redness, nasal congestion, and discharge associated with cluster attacks. The activation of the trigeminal nerve appears to come from a deeper part of the brain called the hypothalamus. The hypothalamus is home to our "internal biologic clock" which regulates our sleep and wake cycles on a 24-hour schedule. Recent imaging studies have shown activation or stimulation of the hypothalamus during a cluster attack.

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