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The discovery of mis-sense mutations in the alpha1A subunit of the P/Q-type calcium channel in patients with familial hemiplegic migraine indicates the potential involvement of dysfunctional ion channels in migraine. The periaqueductal gray (PAG) region of the brainstem modulates craniovascular nociception and, through its role in the descending pain(More)
Patients with primary headache syndromes often describe a distribution of pain that involves both frontal and occipital parts of the head. Such a distribution of pain does not respect the cutaneous sensory innervation of the head which would divide it into anterior (trigeminally innervated) and posterior (spinal nerve root innervated) regions. Studies of(More)
The c-AMP-responsive element binding protein (CREB) and its phosphorylated product (P-CREB) are nuclear proteins expressed after stimulation of pain-producing areas of the spinal cord. There is evidence indicating that central sensitization within dorsal horn neurons is dependent on P-CREB transcriptional regulation. The objectives of the study were to(More)
We have recently shown that injection of the P/Q-type (Ca(v)2.1/alpha(1A)) calcium channel blocker, omega-agatoxin IVA, into the periaqueductal gray (PAG) facilitates meningeal dural stimulation-evoked trigeminal nociceptive processing. We injected the GABA(A) antagonist bicuculline into the PAG in addition to the agatoxin and observed bicuculline's effect(More)
Clinical observations, particularly of the premonitory phase of migraine, suggest the involvement of the hypothalamus in the earliest phases of an attack. Stimulation of the superior sagittal sinus (SSS) in humans produces head pain and permits study of the activated trigeminovascular system in experimental settings. The distribution of neurons expressing(More)
The periaqueductal grey (PAG) region of the brainstem is a known modulator of somatic pain transmission. Migraine is likely to be due to episodic brain dysfunction in pathways involved in the control of pain and other sensory modalities, such as light and sound. To investigate the influence of the PAG on pain transmission from intracranial structures, we(More)
Somatostatin is a neuromodulator in the central nervous system and is involved in the regulation of metabolic and neuroendocrine functions. Recent experimental and clinical findings point to a role for somatostatin in the central processing of nociception. We studied the effects of somatostatin receptor modulation in the posterior hypothalamic area (PH) of(More)
The novel neuropeptides orexin A and B are selectively synthesised in the lateral and posterior hypothalamus and are involved in hypothalamic regulation of autonomic and neuroendocrine functions. Recent findings point also to a role in nociception. As the posterior hypothalamus is involved in the central modulation of nociception we studied the effects of(More)
It is considered that the site of action of the abortive antimigraine compounds acting at serotonin, 5-HT(1B/1D,) receptors (triptans) is the trigeminovascular system. We tested whether there is a non-trigeminal site of action. The 5-HT(1B/1D) agonist, naratriptan, was microinjected into the ventrolateral periaqueductal gray (vlPAG), and activity in the(More)
Functional imaging studies and clinical evidence suggest that structures in the brainstem contribute to migraine pathophysiology with a strong association between the brainstem areas, such as periaqueductal gray (PAG), and the headache phase of migraine. Stimulation of the superior sagittal sinus (SSS) in humans evokes head pain. Second-order neurons in the(More)