Differences in Neuropathology between Nitroglycerin-Induced Mouse Models of Episodic and Chronic Migraine

• Published in: International journal of molecular sciences Vol. 25; no. 7; p. 3706
• Main Authors: Park, Songyi, Jung, Harry, Han, Sang-Won, Lee, Sang-Hwa, Sohn, Jong-Hee
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-04-2024
• Subjects: Animals; anterior cingulate cortex; Brain; Calcitonin Gene-Related Peptide - genetics; chronic migraine; Chronic Pain; Disease Models, Animal; episodic migraine; Hyperalgesia; Mice; Microscopy; Migraine; Migraine Disorders - chemically induced; Migraine Disorders - genetics; Neuropathology; Neuropeptides; Nitrates; nitroglycerin; Nitroglycerin - pharmacology; Pain; Pathophysiology; Pituitary Adenylate Cyclase-Activating Polypeptide; Substance P; trigeminal spinal subnucleus caudalis; vasoactive intestinal peptide; South Korea; vasoactive intestinal peptide; episodic migraine; trigeminal spinal subnucleus caudalis; nitroglycerin; pituitary adenylate cyclase-activating peptide; calcitonin gene-related peptide; chronic migraine; substance P; anterior cingulate cortex
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25073706

Multiple animal models of migraine have been used to develop new therapies. Understanding the transition from episodic (EM) to chronic migraine (CM) is crucial. We established models mimicking EM and CM pain and assessed neuropathological differences. EM and CM models were induced with single NTG or multiple injections over 9 days. Mechanical hypersensitivity was assessed. Immunofluorescence utilized c-Fos, NeuN, and Iba1. Proinflammatory and anti-inflammatory markers were analyzed. Neuropeptides (CGRP, VIP, PACAP, and substance P) were assessed. Mechanical thresholds were similar. Notable neuropathological distinctions were observed in Sp5C and ACC. ACC showed increased c-Fos and NeuN expression in CM (
< 0.001) and unchanged in EM. Sp5C had higher c-Fos and NeuN expression in EM (
< 0.001). Iba1 was upregulated in Sp5C of EM and ACC of CM (
< 0.001). Proinflammatory markers were strongly expressed in Sp5C of EM and ACC of CM. CGRP expression was elevated in both regions and was higher in CM. VIP exhibited higher levels in the Sp5C of EM and ACC of CM, whereas PACAP and substance P were expressed in the Sp5C in both models. Despite similar thresholds, distinctive neuropathological differences in Sp5C and ACC between EM and CM models suggest a role in the EM to CM transformation.