Third, all classes of symptomatic medications, both migraine-specific (such

as ergots and triptans) and nonspecific analgesics (such as opiates and non-narcotic analgesics), are able to cause MOH if they are used excessively.[9] Clinical features of MOH caused by these abortive agents are quite similar, but not necessarily identical. Because BGB324 clinical trial these drugs have different pharmacological actions, it is unlikely that MOH is caused by the specific action of any single causative agent. The more likely, but as yet unproven, explanation is that all drugs share some common mechanism in generating this phenomenon. Finally, in addition to headache, patients with MOH also suffer from other clinical symptoms. These include depressed mood, sleep disturbance, and noncephalic body pain. MOH patients tend to have poor general health and poor quality of life.[10] These nonheadache

manifestations imply that chronic analgesic consumption not only affects nociceptive and pain perception processes, but also alters neural pathways that control vegetative functions. The clinical observations described above lead to the hypothesis that chronic medication may alter the central modulating system that controls nociception and other vegetative functions. This alteration may further affect the already vulnerable nervous systems of those with underlying primary headaches. Activation selleck screening library of the trigeminal system is an essential step in generating all forms of primary headaches. The primary afferents of trigeminal nociceptive fibers innervate pain-sensitive structures, including cranial vessels, meninges, and pericranial muscles and fascias. Activation of trigeminal nociceptive terminals stimulates the release of calcitonin gene-related peptide (CGRP). This

neuropeptide can increase the sensitivity PLEK2 of perivascular nociceptors and dilate cranial vessels. Central axons of the trigeminal ganglionic (TG) neurons terminate onto second-order neurons in the trigeminocervical complex (TCC), which includes the trigeminal nucleus caudalis (TNC), and CGRP release here can facilitate neurotransmission of nociceptive trigeminovascular input.[11] Both TG and TCC neurons are highly plastic, physiologically and anatomically. Their responses can change according to the patterns of their input. Chronic activation modulates the transcription of several proteins that are involved in nociceptive transduction. These modifications result in long-lasting changes in neuronal activity. The increases in response of TG neurons (known as peripheral sensitization) and TCC neurons (known as central sensitization) play major roles in the development of throbbing headache and cutaneous allodynia developed during the attacks of migraine.