Protein kinase Cδ as a neuronal mechanism for headache in a chronic intermittent nitroglycerin model of migraine in mice
| Autor: | Ying He, Zaijie Jim Wang, Robert O. Messing, Yavnika Kashyap, Zuoxiao Shi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Topiramate
Migraine Disorders Population Pharmacology Article Mice Nitroglycerin Animals Medicine education education.field_of_study business.industry Headache medicine.disease Pathophysiology Conditioned place preference Disease Models Animal Protein Kinase C-delta Sumatriptan Anesthesiology and Pain Medicine Neurology Migraine Hyperalgesia Neurology (clinical) Headaches medicine.symptom business medicine.drug |
| Zdroj: | Pain |
| ISSN: | 0304-3959 |
| Popis: | Migraine is one of the most common neurological disorders characterized by recurrent attacks of typically throbbing and unilateral headaches, affecting up to 20% of the population worldwide. Despite the high prevalence and severity of this primary headache disorder, it remains to be a challenge to fully understand and treat migraine headaches. By characterizing and validating a mouse migraine model, this study aimed to investigate the functional contribution of protein kinase C (PKC) isoforms in migraine. In this study, we identified the presence of migraine-like ongoing pain in mice after chronic intermittent treatment with nitroglycerin (NTG). The peptide antagonist of calcitonin gene-related peptide α-CGRP (8-37), but not topiramate nor sumatriptan, effectively blocked ongoing pain and elicited pain relief-induced conditioned place preference in NTG-treated mice. Prominent activation of PKCδ was observed in chronic NTG-treated mice. Functional inhibition of PKCδ significantly attenuated ongoing spontaneous pain in chronic NTG-treated mice. Furthermore, we recapitulated the NTG-triggered migraine behavior in wild-type mice, but not in PKCδ-null mice. In response to repeated administration of NTG, ongoing spontaneous pain was not developed in mice lacking the specific PKC isoform. This study identified the presence of ongoing pain in mice treated with NTG, a known human migraine trigger that closely resembles the common manifestation of spontaneous migraine attacks in humans. These findings demonstrated a critical regulatory role of PKCδ in migraine pathophysiology, which may offer new pharmacological targets for antimigraine treatment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|