Cortico-NRM Influences on Trigeminal Neuronal                 Sensation

We tested the idea that migraine triggers cause cortical activation, which disinhibits craniovascular sensation through the nucleus raphe magnus (NRM) and thus produces the headache of migraine. Stimulation of the dura mater and facial skin activated neurons in the NRM and the trigeminal nucleus. Stimulation of the NRM caused suppression of responses of trigeminal neurons to electrical and mechanical stimulation of the dura mater, but not of the skin. This suppression was antagonized by the iontophoretic application of the 5-HT1B/1D receptor antagonist GR127935 to trigeminal neurons. Migraine trigger factors were simulated by cortical spreading depression (CSD) and light flash. Activity of neurons in the NRM was inhibited by these stimuli. Multiple waves of CSD antagonized the inhibitory effect of NRM stimulation on responses of trigeminal neurons to dural mechanical stimulation but not to skin mechanical stimulation. The cortico-NRM-trigeminal neuraxis might provide a target for a more universally effective migraine prophylactic treatment.

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Responses of spinal trigeminal neurons to noxious stimulation of paranasal cavities – a rat model of rhinosinusitis headache

Cephalalgia ◽

10.1177/0333102420970467 ◽

2020 ◽

pp. 033310242097046

Author(s):

Michael Koch ◽

Julika Sertel-Nakajima ◽

Karl Messlinger

Keyword(s):

Potassium Chloride ◽

Dura Mater ◽

Paranasal Sinuses ◽

Interstitial Fluid ◽

Receptive Fields ◽

Nasal Bone ◽

Afferent Input ◽

Noxious Stimulation ◽

Trigeminal Neurons ◽

Stimulation Of

Background The pathophysiology of headaches associated with rhinosinusitis is poorly known. Since the generation of headaches is thought to be linked to the activation of intracranial afferents, we used an animal model to characterise spinal trigeminal neurons with nociceptive input from the dura mater and paranasal sinuses. Methods In isoflurane anaesthetised rats, extracellular recordings were made from neurons in the spinal trigeminal nucleus with afferent input from the exposed frontal dura mater. Dural and facial receptive fields were mapped and the paranasal cavities below the thinned nasal bone were stimulated by sequential application of synthetic interstitial fluid, 40 mM potassium chloride, 100 µM bradykinin, 1% ethanol (vehicle) and 100 µm capsaicin. Results Twenty-five neurons with input from the frontal dura mater and responses to chemical stimulation of the paranasal cavities were identified. Some of these neurons had additional receptive fields in the parietal dura, most of them in the face. The administration of synthetic interstitial fluid, potassium chloride and ethanol was not followed by significant changes in activity, but bradykinin provoked a cluster of action potentials in 20 and capsaicin in 23 neurons. Conclusion Specific spinal trigeminal neurons with afferent input from the cranial dura mater respond to stimulation of paranasal cavities with noxious agents like bradykinin and capsaicin. This pattern of activation may be due to convergent input of trigeminal afferents that innervate dura mater and nasal cavities and project to spinal trigeminal neurons, which could explain the genesis of headaches due to disorders of paranasal sinuses.

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A potential role for two brainstem nuclei in craniovascular nociception and the triggering of migraine headache

Cephalalgia ◽

10.1177/0333102420960039 ◽

2020 ◽

pp. 033310242096003

Author(s):

Alessandro S Zagami ◽

Sumaiya Shaikh ◽

David Mahns ◽

Geoffrey A Lambert

Keyword(s):

Dura Mater ◽

Cortical Spreading Depression ◽

Migraine Headache ◽

Spreading Depression ◽

Light Flash ◽

Discharge Rate ◽

Indirect Evidence ◽

Second Order ◽

Facial Skin ◽

Migraine Triggers

Aim To use an animal model of migraine to test whether migraine headache might arise from a brainstem-trigeminal nucleus pathway. Methods We measured evoked and spontaneous activity of second-order trigeminovascular neurons in rats to test whether the activity of these neurons increased following the induction of cortical spreading depression or the imposition of light flash – two potential migraine triggers, or headache provokers. We then tested whether drugs that could activate, or inactivate, neurons of the nucleus raphe magnus or the periaqueductal gray matter, would affect any such increases selectively for the dura mater. Results Injection of sodium glutamate (a neuronal excitant) into these two nuclei selectively inhibited the responses of trigeminovascular second-order neurons to dura mater, but not to facial skin, stimulation. Injection of lignocaine (a local anaesthetic) into these nuclei selectively potentiated the responses of these neurons to dura, but not to facial skin, stimulation. Furthermore, injections into either nucleus of glutamate inhibited the increase in the ongoing discharge rate of these neurons produced by cortical spreading depression and light flash. Conclusions These results provide indirect evidence that trigeminovascular nociception may be tightly controlled by these two nuclei, whereas cutaneous trigeminal sensation may be less so. These nuclei may be relays of one possible brainstem-trigeminal pathway that could mediate migraine headache. Modification of neuronal activity in these two nuclei produced by migraine (headache) triggers may lie behind the pain of a migraine attack, at least in some cases.

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Efferent Regulation of the Abdominal Stretch Receptors of the Crayfish

Journal of Experimental Biology ◽

10.1242/jeb.61.3.781 ◽

1974 ◽

Vol 61 (3) ◽

pp. 781-798

Author(s):

O. B. ILYINSKY ◽

D. L. SPIVACHENKO ◽

E. I. SHTIRBU

Keyword(s):

Mechanical Stimulation ◽

Background Activity ◽

Inhibitory Effect ◽

Discharge Frequency ◽

Efferent Control ◽

Close Interaction ◽

Stretch Receptors ◽

Astacus Fluviatilis ◽

The One ◽

Stimulation Of

1. Efferent regulation of the activities of the slowly adapting and fast adapting stretch receptors (the MRO1 and MRO2, respectively) of Astacus fluviatilis was studied. 2. It was shown that the receptors activity is under the efferent control of two central inhibitory neurones: the main inhibitory neurone (MIN) and the accessory neurone (AIN). Their activities were determined by the degree of discharge from the receptors. 3. There was close interaction between the MRO1 and the MIN. The activity of the MIN was determined by the activity of the MRO1 to a higher degree than vice versa; the activity of the MIN was influenced not only by the MRO1 impulses, but by the cessation of those impulses as well (silent periods). The MRO1 could inhibit or excite the MIN, whereas the MIN could inhibit the activity of the MRO1. 4. Interaction between the MRO1 and the MIN could occur during background activity of the MRO1 or of the MIN. In both cases the activity of the initially non-active neurone appeared only after stimulation had been applied to the MRO1. 5. Often each impulse of the MRO1 resulted in a MIN discharge of from 1 to 361 impulses. Sometimes the responses appeared after burst-discharges, induced by mechanical stimulation, of the otherwise inactive MRO1. 6. During interaction between the MRO1 and the MIN, the neurone commencing activity had a higher discharge frequency, if only by 1-2 imp./ sec, than the one firing previously. 7. Under the influence of MIN impulses the response of the MRO1 to stimulation changes from slowly adapting to fast-adapting. 8. The MIN has a slight inhibitory effect on the activity of the MRO2 which is most clearly seen in the course of background activity of the MRO2. The MRO2, however, does not exert much influence on the activity of the MIN. 9. The AIN had much less effect than the MIN on receptors, and the receptors did not naturally evoke AIN impulses. There is, therefore, apparently a more complicated connexion between the receptors and the AIN than between the receptors and the MIN.

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Mechanical stimulation of human BON cells: Gαq involvement in 5-HT release

Gastroenterology ◽

10.1016/s0016-5085(01)80410-8 ◽

2001 ◽

Vol 120 (5) ◽

pp. A83-A83

Author(s):

M KIM ◽

N JAVED ◽

F CHRISTOFI ◽

H COOKE

Keyword(s):

Mechanical Stimulation ◽

Bon Cells ◽

Stimulation Of

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Neural mechanisms of hepatic blood flow response to noxious mechanical stimulation of skin in anesthetized rats

Neuroscience Research ◽

10.1016/s0168-0102(00)81890-8 ◽

2000 ◽

Vol 38 ◽

pp. S174

Author(s):

K Enomoto

Keyword(s):

Blood Flow ◽

Hepatic Blood Flow ◽

Mechanical Stimulation ◽

Neural Mechanisms ◽

Blood Flow Response ◽

Flow Response ◽

Anesthetized Rats ◽

Noxious Mechanical Stimulation ◽

Stimulation Of

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Use of Flexible Materials with a Novel Pressure Driven Equibiaxial Cell Stretching Device for Mechanical Stimulation of Single Mammalian Cells

MRS Proceedings ◽

10.1557/proc-773-n5.6 ◽

2003 ◽

Vol 773 ◽

Author(s):

James D. Kubicek ◽

Stephanie Brelsford ◽

Philip R. LeDuc

Keyword(s):

Cell Fate ◽

Mechanical Stimulation ◽

Mammalian Cells ◽

Cellular Response ◽

Single Cells ◽

Complex Nature ◽

Cellular Behavior ◽

Cell Stretching ◽

Stimulation Of ◽

Pressure Driven

AbstractMechanical stimulation of single cells has been shown to affect cellular behavior from the molecular scale to ultimate cell fate including apoptosis and proliferation. In this, the ability to control the spatiotemporal application of force on cells through their extracellular matrix connections is critical to understand the cellular response of mechanotransduction. Here, we develop and utilize a novel pressure-driven equibiaxial cell stretching device (PECS) combined with an elastomeric material to control specifically the mechanical stimulation on single cells. Cells were cultured on silicone membranes coated with molecular matrices and then a uniform pressure was introduced to the opposite surface of the membrane to stretch single cells equibiaxially. This allowed us to apply mechanical deformation to investigate the complex nature of cell shape and structure. These results will enhance our knowledge of cellular and molecular function as well as provide insights into fields including biomechanics, tissue engineering, and drug discovery.

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