Role of ATP in migraine mechanisms: focus on P2X3 receptors
Abstract Migraine is a major health burden worldwide with complex pathophysiology and multifarious underlying mechanisms. One poorly understood issue concerns the early steps in the generation of migraine pain. To elucidate the basic process of migraine pain further, it seems useful to consider key...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10194-022-01535-4 |
| _version_ | 1797958547468713984 |
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| author | R. Giniatullin A. Nistri |
| author_facet | R. Giniatullin A. Nistri |
| author_sort | R. Giniatullin |
| collection | DOAJ |
| description | Abstract Migraine is a major health burden worldwide with complex pathophysiology and multifarious underlying mechanisms. One poorly understood issue concerns the early steps in the generation of migraine pain. To elucidate the basic process of migraine pain further, it seems useful to consider key molecular players that may operate synergistically to evoke headache. While the neuropeptide CGRP is an important contributor, we propose that extracellular ATP (that generally plays a powerful nociceptive role) is also a major component of migraine headache, acting in concert with CGRP to stimulate trigeminal nociceptive neurons. The aim of the present focused review is to highlight the role of ATP activating its P2X3 membrane receptors selectively expressed by sensory neurons including their nerve fiber terminals in the meninges. Specifically, we present data on the homeostasis of ATP and related purines in the trigeminovascular system and in the CNS; the basic properties of ATP signalling at peripheral and central nerve terminals; the characteristics of P2X3 and related receptors in trigeminal neurons; the critical speed and persistence of P2X3 receptor activity; their cohabitation at the so-called meningeal neuro-immune synapse; the identity of certain endogenous agents cooperating with ATP to induce neuronal sensitization in the trigeminal sensory system; the role of P2X3 receptors in familial type migraine; the current state of P2X3 receptor antagonists and their pharmacological perspectives in migraine. It is proposed that the unique kinetic properties of P2X3 receptors activated by ATP offer an interesting translational value to stimulate future studies for innovative treatments of migraine pain. |
| first_indexed | 2024-04-11T00:20:35Z |
| format | Article |
| id | doaj.art-44183fcff6584798836df7d08d9c9f82 |
| institution | Directory Open Access Journal |
| issn | 1129-2377 |
| language | English |
| last_indexed | 2024-04-11T00:20:35Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-44183fcff6584798836df7d08d9c9f822023-01-08T12:17:00ZengBMCThe Journal of Headache and Pain1129-23772023-01-0124111210.1186/s10194-022-01535-4Role of ATP in migraine mechanisms: focus on P2X3 receptorsR. Giniatullin0A. Nistri1A.I Virtanen Institute, University of Eastern FinlandDepartment of Neuroscience, International School for Advanced Studies (SISSA)Abstract Migraine is a major health burden worldwide with complex pathophysiology and multifarious underlying mechanisms. One poorly understood issue concerns the early steps in the generation of migraine pain. To elucidate the basic process of migraine pain further, it seems useful to consider key molecular players that may operate synergistically to evoke headache. While the neuropeptide CGRP is an important contributor, we propose that extracellular ATP (that generally plays a powerful nociceptive role) is also a major component of migraine headache, acting in concert with CGRP to stimulate trigeminal nociceptive neurons. The aim of the present focused review is to highlight the role of ATP activating its P2X3 membrane receptors selectively expressed by sensory neurons including their nerve fiber terminals in the meninges. Specifically, we present data on the homeostasis of ATP and related purines in the trigeminovascular system and in the CNS; the basic properties of ATP signalling at peripheral and central nerve terminals; the characteristics of P2X3 and related receptors in trigeminal neurons; the critical speed and persistence of P2X3 receptor activity; their cohabitation at the so-called meningeal neuro-immune synapse; the identity of certain endogenous agents cooperating with ATP to induce neuronal sensitization in the trigeminal sensory system; the role of P2X3 receptors in familial type migraine; the current state of P2X3 receptor antagonists and their pharmacological perspectives in migraine. It is proposed that the unique kinetic properties of P2X3 receptors activated by ATP offer an interesting translational value to stimulate future studies for innovative treatments of migraine pain.https://doi.org/10.1186/s10194-022-01535-4MigrainePainHeadacheATPP2X3Trigeminal neurons |
| spellingShingle | R. Giniatullin A. Nistri Role of ATP in migraine mechanisms: focus on P2X3 receptors The Journal of Headache and Pain Migraine Pain Headache ATP P2X3 Trigeminal neurons |
| title | Role of ATP in migraine mechanisms: focus on P2X3 receptors |
| title_full | Role of ATP in migraine mechanisms: focus on P2X3 receptors |
| title_fullStr | Role of ATP in migraine mechanisms: focus on P2X3 receptors |
| title_full_unstemmed | Role of ATP in migraine mechanisms: focus on P2X3 receptors |
| title_short | Role of ATP in migraine mechanisms: focus on P2X3 receptors |
| title_sort | role of atp in migraine mechanisms focus on p2x3 receptors |
| topic | Migraine Pain Headache ATP P2X3 Trigeminal neurons |
| url | https://doi.org/10.1186/s10194-022-01535-4 |
| work_keys_str_mv | AT rginiatullin roleofatpinmigrainemechanismsfocusonp2x3receptors AT anistri roleofatpinmigrainemechanismsfocusonp2x3receptors |