Related Experiment Video
Updated: Sep 4, 2026

Ex Vivo Release of Calcitonin Gene-Related Peptide from the Trigeminovascular System in Rodents
Published on: May 16, 2022
The cerebrospinal fluid-contacting nucleus CGRP-RAMP1-PKA signaling pathway mediates trigeminal neuralgia and its
Bin Gui1,2, Yang Bai1,2, Yijun Zhang1,2
1Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, Xuzhou Medical University, Xuzhou, China.
Background:
Trigeminal neuralgia (TN) is prevalent form of neuropathic pain (NP). Its regulatory circuits and mechanisms remain unclear. The authors' previous work demonstrated that the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) participates in the regulation of NP induced by sciatic nerve injury via the brain-CSF circuit. However, whether it mediates NP caused by trigeminal nerve injury has not been reported.
Methods:
This study used viral retrograde tracing to examine neural projections between the CSF-contacting nucleus and the trigeminal ganglion (TG). Neuronal activity in TN model was assessed using immunofluorescence, and chemogenetic tools were used to test its role in pain behavior. Local calcitonin gene-related peptide (CGRP)-RAMP1-PKA signaling changes and their modulation were analyzed for effects on TN.
Results:
Retrograde tracing confirmed neural projections between the CSF-contacting nucleus and the TG. In TN model rats, elevated c-Fos expression indicated its activation. Chemogenetic activation induced hyperalgesia in normal rats, whereas its inhibition reduced pain in TN rats. Molecular analyses revealed upregulation of CGRP, RAMP1, and components of the PKA pathway within the nucleus. Pathway inhibition via RAMP1 knockdown or olcegepant administration attenuated pain, with knockdown effect being reversible by cAMP.
Conclusions:
This study reveals that the CSF-contacting nucleus is activated during TN and participates in central pain regulation through its local CGRP-RAMP1-PKA signaling pathway. Intervening in this pathway effectively modulates pain behavior, suggesting that this nucleus and its signaling system may represent novel therapeutic targets for treating TN. These findings provide experimental evidence for understanding the central mechanisms of TN and developing analgesic strategies.
Related Concept Videos
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Parasympathetic Signaling
The effects of...
GPCRs Regulate Adenylyl Cylase Activity
Two...
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Enzyme-linked Receptors
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...