G.A. Lambert

Brainstem Influences on the Cephalic Circulation: Experimental Data From Cat and Monkey of Relevance to the Mechanism of Migraine

SYNOPSIS

Neural Processing of Craniovascular Pain: A Synthesis of the Central Structures Involved in Migraine

SYNOPSIS

Differential effects on the internal and external carotid circulation of the monkey evoked by locus coeruleus stimulation.

Electrical stimulation at 1-200/s of the locus coeruleus in 12 Macaca nemestrina monkeys caused a frequency-dependent drop in vascular resistance in the extracerebral circulation which was twice as great on the side stimulated. Accompanying this dilatation of the extracerebral vasculature was a frequency-dependent rise in internal carotid vascular resistance, usually seen only on the side ipsilateral to stimulation. This constrictor response was maximal at low frequencies of stimulation and minimal at higher frequencies. Neither the dilator nor constrictor responses were affected by sectioning of the vagus nerve or sympathetic trunk in the neck. The simultaneous occurrence of intracranial vasoconstriction and extracranial vasodilatation has not been demonstrated previously, and bears a remarkable resemblance to the vascular changes of migraine.

The Mode of Action of Migraine Triggers: A Hypothesis

Objectives.— To review conjectured modes of action of migraine triggers and to present a new hypothesis about them.

Stimulation of cranial vessels excites nociceptive neurones in several thalamic nuclei of the cat

SummaryExtracellular recordings were made in the thalamus of cats anaesthetized with chloralose and urethane following electrical, mechanical and chemical stimulation of the superior sagittal sinus or middle meningeal artery. Facial receptive fields were looked for using electrical and mechanical stimuli. The locations of fifty-six cells were verified histologically. Twenty six cells were located in the ventroposteromedial nucleus (VPM) and six in its ventral periphery (VPMvp). All units in VPM had facial receptive fields, usually involving the first trigeminal division. Cells with nociceptive receptive fields or responding to the craniovascular application of bradykinin were often found in the periphery or “shell” region of VPM. Other craniovascular nociceptive cells were found in VPMvp, in the posterior group and in the intralaminar complex. This study shows that craniovascular afferents in the cat project to several thalamic nuclei and implicate VPM especially in craniovascular nociception.

Comparative effects of stimulation of the trigeminal ganglion and the superior sagittal sinus on cerebral blood flow and evoked potentials in the cat

The superior sagittal sinus (SSS) and the trigeminal ganglion (Vg) of anesthetized cats were stimulated electrically and field potentials in the upper cervical spinal cord and regional cerebral blood flow were recorded. Stimulation of the entire ganglion produced smaller field potential changes in two regions (medioventral area (MVA); dorsolateral area (DLA] of the upper spinal cord than did stimulation of the sagittal sinus (Vg/SSS response ratio = 17% for the MVA and 48% for the DLA). Stimulation of the trigeminal ganglion increased blood flow in only the frontal and parietal cortices (+93% and +33%), whereas stimulation of the sinus produced both larger changes in these areas (+137% and +139%) and also produced changes in regional cerebral blood flow in the thalamus (+122%).

Stimulation of the Trigeminal ganglion increases flow in the extracerebral but not the cerebral circulation of the monkey

The trigeminal ganglion of 9 anesthetized paralysed artificially ventilated Macaca nemestrina monkeys was electrically stimulated with frequencies varying from 0.2 to 200 Hz. This stimulation led to a frequency-dependent decrease in external carotid resistance but no significant change in internal carotid resistance was recorded. The response is probably mediated as previously described in the cat, i.e. predominantly through the greater superficial petrosal branch of the facial nerve and a small proportion through antidromic activation of the trigeminal system. Elucidation of the physiological and pharmacological mechanisms underlying such a response may aid in a better understanding of the pathophysiology of vascular headache.

The spinal cord processing of input from the superior sagittal sinus: pathway and modulation by ergot alkaloids

The effects of ergot alkaloids on field potentials and unit responses produced in the upper cervical spinal cord by stimulation of the superior sagittal sinus (SSS) were examined in 57 anesthetized cats. Electrical stimulation of the SSS produced field potentials and single-unit responses at latencies of 5-20 ms. Field potentials were abolished by section of the first division of the trigeminal nerve but were unaffected or increased by section of the upper cervical nerves. Field potentials were reduced or abolished by intravenous injection of ergotamine or dihydroergotamine (DHE). The evoked response of 41 units (34.4%) were suppressed by either i.v. or iontophoretic administration of ergotamine, DHE or ergometrine. The results suggest that ergot alkaloids exert an effect at a spinal cord relay centre which receives trigeminally mediated input from cranial blood vessels.

Effects of locus coeruleus stimulation on carotid vascular resistance in the cat

The locus coeruleus was stimulated in 62 cats in order to investigate the effect on cephalic blood flow and cephalic vascular resistance. Flow was measured by electromagnetic flow probes applied to the common carotid artery. Stimulation over a range of frequencies (0.2-200 s-1) produced a frequency-dependent fall in carotid vascular resistance, greater on the ipsilateral side. This response was not affected by either cervical sympathectomy or spinal cord section. The response was blocked by bilateral section of the facial nerve but was not abolished by classical cholinergic, histaminergic or adrenergic blocking agents. Stimulation of the locus coeruleus also resulted in a pressor response through spinal mechanisms in which coeruleo-hypothalamic projections were not involved. A post-stimulation constriction in the carotid vasculature followed the dilator response and was attributed to release of catecholamines from the adrenal medulla.

Activation of trigeminovascular neurons by glyceryl trinitrate.

The effect of intra-carotid arterial infusions of glyceryl trinitrate (GTN), a substance known to precipitate headache, including migraine, upon the spontaneous activity of trigeminal neurons with craniovascular input was studied in cats. Second-order craniovascular neurons which received sensory input from the superior sagittal sinus were recorded in the trigeminal nucleus caudalis. Infusions of GTN were administered via a catheter inserted retrogradely into the common carotid artery through the lingual artery. Infusions of GTN (100 microg kg(-1) min(-1) in a volume of 2 ml min(-1)) increased the mean basal discharge rate of all second-order neurons to 239+/-47% of control. GTN produced a fall in mean blood pressure, but there was no correlation between this fall and the changes in discharge rate. GTN infusions sensitised neurons to the effects of electrical stimulation of the superior sagittal sinus, but not to subsequent GTN infusions. Infusions of similar volumes of vehicle did not alter the discharge rate of neurons. We conclude that GTN activates craniovascular sensory pathways at a site at, or peripheral to, the second-order neuron and that such an action may account for at least the acute-onset headache induced by GTN.