Serotonin depletion increases nociception-evoked trigeminal NMDA receptor phosphorylation.
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.
Maneepak
Montree
M
Faculty of Medicine, Chulalongkorn University-Physiology, Bangkok, Thailand.
le Grand
Supang
S
Srikiatkhachorn
Anan
A
D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D014276:Trigeminal Nerve / Q000378:metabolism*; D014278:Trigeminal Nuclei / Q000378:metabolism*; D010133:p-Chloroamphetamine / Q000494:pharmacology
C409466:NR1 NMDA receptor; D016761:Oncogene Proteins v-fos; D016194:Receptors, N-Methyl-D-Aspartate; D018490:Serotonin Agents; D012701:Serotonin; D010133:p-Chloroamphetamine