Molecular Mechanisms of Sensitization of Pain-transducing P2X3 Receptors by the Migraine Mediators CGRP and NGF

@article{Giniatullin2008MolecularMO,
  title={Molecular Mechanisms of Sensitization of Pain-transducing P2X3 Receptors by the Migraine Mediators CGRP and NGF},
  author={Rashid Giniatullin and Andrea Nistri and E. Fabbretti},
  journal={Molecular Neurobiology},
  year={2008},
  volume={37},
  pages={83-90}
}
Migraine headache originates from the stimulation of nerve terminals of trigeminal ganglion neurons that innervate meninges. Characteristic features of migraine pain are not only its delayed onset but also its persistent duration. Current theories propose that endogenous substances released during a migraine attack (the neuropeptide calcitonin gene-related peptide [CGRP] and the neurotrophin nerve growth factor [NGF]) sensitize trigeminal neurons to transmit nociceptive signals to the brainstem… 
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TLDR
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TLDR
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TLDR
This work investigated whether neutralizing NGF might change the function of P2X3 receptors natively coexpressed with NGF receptors on cultured mouse trigeminal neurons and outlined the important contribution by NGF signaling to nociception of trigemINAL sensory neurons, which could be counteracted by anti-NGF pretreatment.
Delayed Upregulation of ATP P2X3 Receptors of Trigeminal Sensory Neurons by Calcitonin Gene-Related Peptide
TLDR
A new form of selective, slow upregulation of nociceptive P2X3 receptors on trigeminal neurons by CGRP is demonstrated, which might contribute to pain sensitization and represents a model of neuronal plasticity in response to a migraine mediator.
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TLDR
The present data indicate a novel mechanism for enhancing P2X3 receptor expression and function in trigeminal sensory neurons by CGRP via CREB phosphorylation, which could serve as a powerful process to amplify and prolong pain mediated by P2x3 receptors.
Mechanisms Mediating the Enhanced Gene Transcription of P2X 3 Receptor by Calcitonin Gene-related Peptide in
TLDR
The present data indicate a novel mechanism for enhancing P2X3 receptor expression and function in trigeminal sensory neurons by CGRP via CREB phosphorylation, which could serve as a powerful process to amplify and prolong pain mediated by P2x3 receptors.
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TLDR
Culturing did not prevent differential receptor upregulation by algogenic substances like NGF or serotonin, indicating that chronic application led to distinct plastic changes in the molecular mechanisms mediating pain on trigeminal nociceptors.
Calcitonin gene–related peptide does not excite or sensitize meningeal nociceptors: Implications for the pathophysiology of migraine
TLDR
The results of this study suggest that CGRP effects in the meninges, including meningeal vasodilatation, are not sufficient to activate or sensitizeMeningeal nociceptors.
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TLDR
It is shown that CGRP is coexpressed with brain‐derived neurotrophic factor (BDNF) in a large subset of adult rat trigeminal ganglion neurons in vivo, and BDNF‐immunoreactivity is present in dense core vesicles of unmyelinated axons and axon terminals in the subnucleus caudalis of the spinal trigEMinal nucleus.
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TLDR
It is argued that the full‐length peptides C GRP and substance P might play distinct roles in the activity‐dependent modulation of cholinergic neurotransmission, by inhibiting background noise in the case of CGRP or by reducing excessive excitation in the cases of substance P.
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TLDR
Monitoring the effects of NGF on the increase in intracellular calcium concentration following exposure to capsaicin indicates that the crucial early pathway activated by NGF involves PI3K, while PKC and CaMK II are also involved, probably at subsequent stages of the NGF‐activated signalling pathway.
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TLDR
The results suggest that inflammatory mediators sensitize nociceptors through phosphorylation of P2x3 and P2X2/3 ion channels or associated proteins.
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