Conflict of Interest: None
Serotonin Depletion Increases Nociception-Evoked Trigeminal NMDA Receptor Phosphorylation
Article first published online: 11 FEB 2009
© 2009 the Authors. Journal compilation © 2009 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 49, Issue 3, pages 375–382, March 2009
How to Cite
Maneepak, M., Le Grand, S. and Srikiatkhachorn, A. (2009), Serotonin Depletion Increases Nociception-Evoked Trigeminal NMDA Receptor Phosphorylation. Headache: The Journal of Head and Face Pain, 49: 375–382. doi: 10.1111/j.1526-4610.2009.01341.x
- Issue published online: 25 FEB 2009
- Article first published online: 11 FEB 2009
- Accepted for publication September 22, 2008.
- low serotonin;
- NMDA receptor phosphorylation;
- trigeminal nociception;
- dural inflammation;
Objective.— To investigate the effect of serotonin depletion on phosphorylation and expression of NR1 subunit of N-methyl-D-aspartate (NMDA) receptor in trigeminal nucleus caudalis (TNC), and on trigeminal nociception evoked by dural inflammation.
Background.— Migraine is associated with low serotonin condition and an increased neuronal excitability. NMDA receptor is implicated in central plasticity change that leads to neural sensitization. Alteration in NMDA receptor phosphorylation or expression in TNC may be responsible for increased trigeminal nociception in serotonin-depleted state.
Methods.— Adult male Wistar rats were separated into normal and low serotonin groups. Serotonin was depleted by intraperitoneal injection with para-chlorophenylalanine 3 days before the experiment. Trigeminal nociception was induced by applying inflammatory soup on exposed dura. Two hours after induction, phosphorylated NR1, NR1, and Fos expressions were studied in TNC by immunohistochemistry.
Results.— Dural application of inflammatory soup led to the activation of trigeminal nociceptive system as well as the phosphorylation of NR1, which were further enhanced in the low serotonin condition. There was a strong relationship between NR1 phosphorylation and trigeminal nociception. However, neither meningeal inflammation nor serotonin depletion altered NR1 expression.
Conclusions.— Low serotonin condition facilitates dural inflammation-induced NR1 phosphorylation and trigeminal nociception. It is suggested that the mechanism of nociceptive facilitation in serotonin-depleted state may involve the increase in NR1 phosphorylation rather than the upregulation of NR1 subunit of NMDA receptor.