Abstract
Dysfunction of the descending circuitry that modulates nociceptive processing is thought to facilitate primary headache disorders such as migraine and cluster headache, either by reducing inhibition or increasing facilitation of neural signals. The identification of novel neurotransmitter systems (orexinergic, cannabinoid and dopaminergic) within this descending pathway and their interaction with 5-HT(1B/1D) (triptan) receptors provides important clues about several of the risk factors and comorbidities associated with primary headache disorders and indicates that triptans exert central as well as peripheral activity. Current research supports the early treatment of primary headache disorders in order to prevent structural changes in the brain and to minimize dysfunction in the descending modulation of pain control.
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