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Copyright of Headache: The Journal of Head & Face Pain is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article considers physical basis for formation and propagation of sound and its psychophysical perception by living creatures. The authors suggest an algorithm of living creatures’ identification by the voice timbre and the algorithm’s practical realization by artificial neural networks, by initialization of a conversation by the robot in order to reduce ambiguity of responses and to improve the quality of recognition in real-time mode.

The study describes methodological techniques and results of geophysical well logging and seismic data interpretation by means of trainable neural networks. Objects of research are wells and seismic materials of Talakan field. The article also presents forecast of construction and reservoir properties of Osa horizon. The paper gives an example of creation of geological (lithological -facial) model of the field based on developed methodical techniques of complex interpretation of geologicgeophysical data by trainable neural network. The constructed lithological -facial model allows specifying a geological structure of the field. The developed methodical techniques and the trained neural networks may be applied to adjacent sites for research of carbonate horizons.

Background: The terminal branches of the trigeminal nerve in meninges are supposed to be the origin site of migraine pain. The main function of these peripheral sensory axons is the initiation and propagation of spikes in the orthodromic direction to the second order neurons in the brainstem. The stimulation of the trigeminal ganglion induces the release of the neuropeptide CGRP in meninges suggesting the antidromic propagation of excitation in these fibers. However, the direct evidence on antidromic spike traveling in meningeal afferents is missing. Methods: By recording of spikes from peripheral or central parts of the trigeminal nerve in rat meninges, we explored their functional activity and tested the expression of ATP-, serotonin-, and capsaicin-gated receptors in the distal vs. proximal parts of these nerves. Results: We show the significant antidromic propagation of spontaneous spikes in meningeal nerves which was, however, less intense than the orthodromic nociceptive traffic due to higher number of active fibers in the latter. Application of ATP, serotonin and capsaicin induced a high frequency nociceptive firing in peripheral processes while, in central parts, only ATP and capsaicin were effective. Disconnection of nerve from trigeminal ganglion dramatically reduced the tonic antidromic activity and attenuated the excitatory action of ATP. Conclusion: Our data indicate the bidirectional nociceptive traffic and dissimilar expression of P2X, 5-HT and TRPV1 receptors in proximal vs. distal parts of meningeal afferents, which is important for understanding the peripheral mechanisms of migraine pain. [ABSTRACT FROM AUTHOR]

Extracellular ATP and serotonin (5-HT) are powerful triggers of nociceptive firing in the meninges, a process supporting headache and whose cellular mechanisms are incompletely understood. The current study aimed to develop, with the neurosimulator NEURON, a novel approach to explore in silico the molecular determinants of the long-lasting, pulsatile nature of migraine attacks. The present model included ATP and 5-HT release, ATP diffusion and hydrolysis, 5-HT uptake, differential activation of ATP P2X or 5-HT3 receptors, and receptor subtype-specific desensitization. The model also tested the role of branched meningeal fibers with multiple release sites. Spike generation and propagation were simulated using variable contribution by potassium and sodium channels in a multi-compartment fiber environment. Multiple factors appeared important to ensure prolonged nociceptive firing potentially relevant to long-lasting pain. Crucial roles were observed in: (i) co-expression of ATP P2X2 and P2X3 receptor subunits; (ii) intrinsic activation/inactivation properties of sodium Nav1.8 channels; and (iii) temporal and spatial distribution of ATP/5-HT release sites along the branches of trigeminal nerve fibers. Based on these factors we could obtain either persistent activation of nociceptive firing or its periodic bursting mimicking the pulsating nature of pain. In summary, our model proposes a novel tool for the exploration of peripheral nociception to test the contribution of clinically relevant factors to headache including migraine pain. [ABSTRACT FROM AUTHOR]

Peripheral mechanisms of primary headaches such as a migraine remain unclear. Meningeal afferents surrounded by multiple mast cells have been suggested as a major source of migraine pain. Extracellular ATP released during migraine attacks is a likely candidate for activating meningeal afferents via neuronal P2X receptors. Recently, we showed that ATP also increased degranulation of resident meningeal mast cells (Nurkhametova et al., 2019). However, the contribution of ATP-induced mast cell degranulation in aggravating the migraine pain remains unknown. Here we explored the role of meningeal mast cells in the pro-nociceptive effects of extracellular ATP. The impact of mast cells on ATP mediated activation of peripheral branches of trigeminal nerves was measured electrophysiologically in the dura mater of adult wild type (WT) or mast cell deficient mice. We found that a spontaneous spiking activity in the meningeal afferents, at baseline level, did not differ in two groups. However, in WT mice, meningeal application of ATP dramatically (24.6-fold) increased nociceptive firing, peaking at frequencies around 10 Hz. In contrast, in mast cell deficient animals, ATP-induced excitation was significantly weaker (3.5-fold). Application of serotonin to meninges in WT induced strong spiking. Moreover, in WT mice, the 5-HT3 antagonist MDL-7222 inhibited not only serotonin but also the ATP induced nociceptive firing. Our data suggest that extracellular ATP activates nociceptive firing in meningeal trigeminal afferents via amplified degranulation of resident mast cells in addition to direct excitatory action on the nerve terminals. This highlights the importance of mast cell degranulation via extracellular ATP, in aggravating the migraine pain. [ABSTRACT FROM AUTHOR]

The pro-nociceptive role of glutamate in the CNS in migraine pathophysiology is well established. Glutamate, released from trigeminal afferents, activates second order nociceptive neurons in the brainstem. However, the function of peripheral glutamate receptors in the trigeminovascular system suggested as the origin site for migraine pain, is less known. In the current project, we used calcium imaging and patch clamp recordings from trigeminal ganglion (TG) neurons, immunolabelling, CGRP assay and direct electrophysiological recordings from rat meningeal afferents to investigate the role of glutamate in trigeminal nociception. Glutamate, aspartate, and, to a lesser extent, NMDA under free-magnesium conditions, evoked calcium transients in a fraction of isolated TG neurons, indicating functional expression of NMDA receptors. The fraction of NMDA sensitive neurons was increased by the migraine mediator CGRP. NMDA also activated slowly desensitizing currents in 37% of TG neurons. However, neither glutamate nor NMDA changed the level of extracellular CGRP. TG neurons expressed both GluN2A and GluN2B subunits of NMDA receptors. In addition, after removal of magnesium, NMDA activated persistent spiking activity in a fraction of trigeminal nerve fibers in meninges. Thus, glutamate activates NMDA receptors in somas of TG neurons and their meningeal nerve terminals in magnesium-dependent manner. These findings suggest that peripherally released glutamate can promote excitation of meningeal afferents implicated in generation of migraine pain in conditions of inherited or acquired reduced magnesium blockage of NMDA channels and support the usage of magnesium supplements in migraine. [ABSTRACT FROM AUTHOR]

Abstract Background Recent discovery of mechanosensitive Piezo receptors in trigeminal ganglia suggested the novel molecular candidate for generation of migraine pain. However, the contribution of Piezo channels in migraine pathology was not tested yet. Therefore, in this study, we explored a potential involvement of Piezo channels in peripheral trigeminal nociception implicated in generation of migraine pain. Methods We used immunohistochemistry, calcium imaging, calcitonin gene related peptide (CGRP) release assay and electrophysiology in mouse and rat isolated trigeminal neurons and rat hemiskulls to study action of various stimulants of Piezo receptors on migraine-related peripheral nociception. Results We found that essential (35%) fraction of isolated rat trigeminal neurons responded to chemical Piezo1 agonist Yoda1 and about a half of Yoda1 positive neurons responded to hypo-osmotic solution (HOS) and a quarter to mechanical stimulation by focused ultrasound (US). In ex vivo hemiskull preparation, Yoda1 and HOS largely activated persistent nociceptive firing in meningeal branches of trigeminal nerve. By using our novel cluster analysis of pain spikes, we demonstrated that 42% of fibers responded to Piezo1 agonist and 20% of trigeminal fibers were activated by Yoda1 and by capsaicin, suggesting expression of Piezo receptors in TRPV1 positive peptidergic nociceptive nerve fibers. Consistent with this, Yoda1 promoted the release of the key migraine mediator CGRP from hemiskull preparation. Conclusion Taken together, our data suggest the involvement of mechanosensitive Piezo receptors, in particular, Piezo1 subtype in peripheral trigeminal nociception, which provides a new view on mechanotransduction in migraine pathology and suggests novel molecular targets for anti-migraine medicine. Highlights • Migraine originating from meninges is characterized by pulsating pain and mechanical allodynia. • Piezo receptors expressed in meninges can be activated by mechanical or chemical stimuli such as Yoda1. • Stimulation of Piezo receptors activates trigeminal neurons and triggers the release of CGRP. • Cluster spike analysis revealed expression of Piezo1 receptors in nociceptive fibers of the trigeminal nerve. • Piezo receptors can be involved in generation of migraine pain. [ABSTRACT FROM AUTHOR]