The trigemino-cervical complex. Integration of peripheral and central pain mechanisms in primary headache syndromes

Abstract

The activation of the trigeminal nociceptive system is the neural substrate of pain in primary headache syndromes such as migraine and cluster headache. The nociceptive inflow from the meninges to the spinal cord is relayed in brainstem neurones of the trigemino-cervical complex (TCC). Two important mechanisms of pain transmission are reviewed: convergence of nociceptive trigeminal and cervical afferents and sensitization of trigemino-cervical neurones. These mechanisms have clinical correlates such as hyperalgesia, allodynia, spread and referral of pain to trigeminal or cervical dermatomes. Neurones in the TCC are subject to a modulation of pain-modulatory circuits in the brainstem such as the periaqueductal grey (PAG). Recent experimental and clinical findings of a modulation of these pain processes are discussed. The review focuses on TCC neurones as integrative relay neurones between peripheral and central pain mechanisms. The understanding of these mechanisms has implications for the understanding of the clinical phenomenology in primary headache syndromes and the development of therapeutical options.