Burstein, Rami, Hiroyoshi Yamamura, Amy Malick, and Andrew M. Strassman. Chemical stimulation of the intracranial dura induces enhanced responses to facial in brain stem trigeminal neurons. J. Neurophysiol. 79: 964–982, 1998. activation sensitization primary afferent neurons innervating meninges have been postulated as possible causes certain headaches. This sensitization, however, cannot explain extracranial hypersensitivity that often accompanies headache. The goal this study was test...

Abstract The morphology of 35 vestibular neurons whose firing rate was related to vertical eye movements studied by injection horseradish peroxidase intracellularly into physiologically identified axons in alert squirrel monkeys. injected cells were readily classified four main groups. One group cells, down position‐vestibular‐pause (down PVPs; N = 12), increased their during downward positions, paused saccades, and located the medial nucleus (MV) adjacent ventrolateral (VLV). They had that...

Saccadic burst neurons in the pontine reticular formation have been implicated generation of saccades horizontal plane on basis lesion and extracellular recording studies cat monkey. In present study, saccadic were anatomically physiologically characterized with intraaxonal injection horseradish peroxidase alert squirrel A population found that appear analogous to excitatory (EBNs) described previously cat. All are located caudal a major axonal projection ipsilateral abducens nucleus....

Intracranial headaches such as that of migraine are generally accepted to be mediated by prolonged activation meningeal nociceptors but the mechanisms responsible for nociceptor poorly understood. In this study, we examined hypothesis can activated locally through a neuroimmune interaction with resident mast cells, granulated immune cells densely populate dura mater. Using in vivo electrophysiological single unit recording rat observed degranulation dural using intraperitoneal administration...

Abstract The anatomical characteristics of vestibular neurons, which are involved in controlling the horizontal vestibulo‐ocular reflex, were studied by injecting horseradish peroxidase (HRP) into neurons whose response during spontaneous eye movements had been characterized alert squirrel monkeys. Most injected with HRP that axons projecting to abducens nucleus or medial rectus subdivision oculomotor discharge rates related position and velocity. Three morphological types cells firing...

Functioning of the glymphatic system, a network paravascular tunnels through which cortical interstitial solutes are cleared from brain, has recently been linked to sleep and traumatic brain injury, both can affect progression migraine. This led us investigate connection between migraine system. Taking advantage novel in vivo method we developed using two-photon microscopy visualize space (PVS) naive uninjected mice, show that single wave spreading depression (CSD), an animal model aura,...

Abstract The distribution of fos‐like‐immunoreactivity (fos‐LI) in the medullary and upper cervical dorsal horn was examined following noxious facial stimulation, order to evaluate use fos as a marker for neuronal activation trigeminal nociceptive pathways. Control animals that received urethane anesthesia no stimulation showed substantial bilateral labeling complex restricted one rostrocaudal level, at transition between (nucleus caudalis) nucleus interpolaris. Noxious mechanical (pinch)...

Functional magnetic resonance imaging was used to image pain-associated activity in three levels of the neuraxis: medullary dorsal horn, thalamus, and primary somatosensory cortex. In nine subjects, noxious thermal stimuli (46°C) were applied facial skin at sites within divisions trigeminal nerve (V1, V2, V3) also ipsilateral thumb. Anatomical functional data acquired capture activation across spinothalamocortical pathway each individual. Significant observed spinal nucleus medulla lower...

Abstract Migraine is among the most common types of pain, but its mechanisms are poorly understood. A growing body evidence points to a critical role calcitonin gene–related peptide (CGRP) in pathophysiology migraine headache. During migraine, CGRP thought be released from peripheral endings perivascular meningeal nociceptors primary and promote vasodilatation. current hypothesis suggests that related vasodilatation results activation sensitization, leading generation However, direct...

Calcitonin gene-related peptide (CGRP), the most abundant neuropeptide in primary afferent sensory neurons, is strongly implicated pathophysiology of migraine headache, but its role still equivocal. As a new approach to treatment, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs) were developed reduce availability CGRP, and found effective reducing frequency chronic episodic migraine. We recently tested effect fremanezumab (TEV-48125), CGRP-mAb, on activity second-order trigeminovascular...

Abstract Electrophysiological and intracellular labelling studies in the cat have identified a population of saccadic burst neurons medullary reticular formation that an inhibitory, monosynaptic projection to contralateral abducens nucleus. In present study, intraaxonal recording injection horseradish peroxidase were used identify characterize corresponding inhibitory (IBNs) alert squirrel monkey. Squirrel monkey IBNs are located ventral caudal nucleus project contralaterally abducens....

Intracranial headaches such as migraine are thought to result from activation of sensory trigeminal pain neurons that supply intracranial blood vessels and the meninges, also known meningeal nociceptors. Although mechanism underlying triggering is not completely understood, our previous work indicates local inflammatory dural mast cells can provoke a persistent sensitization Given potential importance it important understand which cell-derived mediators interact with nociceptors promote...

A large body of evidence supports an important role for calcitonin gene-related peptide (CGRP) in migraine pathophysiology. This gave rise to a global effort develop new generation therapeutics that inhibit the interaction CGRP with its receptor migraineurs. Recently, class such drugs, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs), were found be effective reducing frequency migraine. The purpose this study was better understand how CGRP-mAb fremanezumab (TEV-48125) modulates...

Abstract Microglia survey and directly contact neurons in both healthy damaged brain, but the mechanisms functional consequences of these contacts are not yet fully elucidated. Combining two-photon imaging patch clamping, we have developed an acute experimental model for studying role microglia CNS excitotoxicity induced by neuronal hyperactivity. Our allows us to simultaneously examine effects repetitive supramaximal stimulation on axonal morphology, membrane potential, microglial...

Background Administration of onabotulinumtoxinA (BoNT-A) to peripheral tissues outside the calvaria reduces number days chronic migraine patients experience headache. Because headache phase a attack, especially those preceded by aura, is thought involve activation meningeal nociceptors endogenous stimuli such as changes in intracranial pressure (i.e. mechanical) or chemical irritants that appear meninges result yet-to-be-discovered sequence molecular/cellular events triggered we sought...

Background The presence of calcitonin gene-related peptide and its receptors in multiple brain areas peripheral tissues previously implicated migraine initiation many associated symptoms raises the possibility that humanized monoclonal anti-calcitonin antibodies (CGRP-mAbs) can prevent by modulating neuronal behavior inside outside brain. Critical to our ability conduct a fair discussion over mechanisms action CGRP-mAbs prevention is data generation determines which possible central sites...

Current understanding of the origin occipital headache falls short distinguishing between cause and effect. Most preclinical studies involving trigeminovascular neurons sample that are responsive to stimulation dural areas in anterior 2/3 cranium periorbital skin. Hypothesizing may involve activation meningeal nociceptors innervate posterior ⅓ dura, we sought map course dura overlying cerebellum. Using AAV-GFP tracing single-unit recording techniques male rats, found C2–C3 DRGs fossa; nearly...

Objective Cortical spreading depression (CSD) has long been implicated in migraine attacks with aura. The process by which CSD, a cortical event that occurs within the blood–brain barrier (BBB), results nociceptor activation outside BBB is likely mediated multiple molecules and cells. objective of this study was to determine whether CSD activates immune cells inside (pia), (dura), or both, if so, when. Methods Investigating cellular events meninges shortly after we used vivo two‐photon...