5yr
Repeated oxytocin prevents central sensitization by regulating synaptic plasticity via oxytocin receptor in a chronic migraine mouse model - The Journal of Headache and Pain
Source : https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-021-01299-3
Background Central sensitization is one of the characters of chronic migraine (CM). Aberrant synaptic plasticity can induce central sensitization. Oxytocin (OT), which is a hypothalamic hormone, plays an important antinociceptive role. However, the antinociceptive effect of OT and the underlying mechanism in CM remains unclear.
Key Point
• Conclusion/Relevance: “Our findings demonstrate that repeated intranasal OT [oxytocin] eliminates central sensitization by regulating synaptic plasticity via OTR [oxytocin receptor] in CM [chronic migraine]. The effect of OT has closely associated with the down-regulation of AC1/PKA/pCREB signaling pathway, which is activated in CM model. Repeated intranasal OT may be a potential candidate for CM prevention.”
• In this preclinical study, researchers assessed the preventive effects of OT in CM mouse models. They noted that OTR expression in the trigeminal nucleus caudalis (TNC) was increased, and continual intranasal OT administration could heighten baseline thresholds triggered by nitroglycerin, as well as ease central sensitization in the TNC.
• The researchers also found that OT could mediate synaptic plasticity via inhibition of the overexpression of phosphorylated NR2B, synaptic plasticity-related proteins, and the restoration of abnormal synaptic structural changes.
• The authors wrote, “The AC1/PKA/pCREB pathway, which was downstream of OTR and regulated the NMDA receptor function, was also suppressed after OT treatment, suggesting that this pathway is a possible mechanism underlying the OT-mediated effect. However, these effects of OT were prevented by an OTR antagonist. These results were consistent with our hypothesis that OT could alleviate central sensitization by regulating synaptic plasticity via OTR.”
• Conclusion/Relevance: “Our findings demonstrate that repeated intranasal OT [oxytocin] eliminates central sensitization by regulating synaptic plasticity via OTR [oxytocin receptor] in CM [chronic migraine]. The effect of OT has closely associated with the down-regulation of AC1/PKA/pCREB signaling pathway, which is activated in CM model. Repeated intranasal OT may be a potential candidate for CM prevention.”
• In this preclinical study, researchers assessed the preventive effects of OT in CM mouse models. They noted that OTR expression in the trigeminal nucleus caudalis (TNC) was increased, and continual intranasal OT administration could heighten baseline thresholds triggered by nitroglycerin, as well as ease central sensitization in the TNC.
• The researchers also found that OT could mediate synaptic plasticity via inhibition of the overexpression of phosphorylated NR2B, synaptic plasticity-related proteins, and the restoration of abnormal synaptic structural changes.
• The authors wrote, “The AC1/PKA/pCREB pathway, which was downstream of OTR and regulated the NMDA receptor function, was also suppressed after OT treatment, suggesting that this pathway is a possible mechanism underlying the OT-mediated effect. However, these effects of OT were prevented by an OTR antagonist. These results were consistent with our hypothesis that OT could alleviate central sensitization by regulating synaptic plasticity via OTR.”