title: Up-regulation of calcitonin gene-related peptide in trigeminal ganglion following chronic exposure to paracetamol in a CSD migraine animal model.
abstract: Previously, our group has demonstrated that chronic paracetamol (APAP) treatment induces alterations to the trigeminovascular nociceptive system in the cortical spreading depression (CSD) migraine animal model. The calcitonin gene related peptide (CGRP) is a key neuropeptide involved in the activation of the trigeminovascular nociceptive system. Therefore, this study examined the expression levels of CGRP in the trigeminal ganglion (TG) after chronic APAP exposure (0, 15, and 30 days) using a CSD model. Rats were divided into control, CSD only, APAP only and APAP treatment with CSD groups. A single injection (i.p.) of APAP (200 mg/kg body weight) was given to the 0-day APAP-treated groups, while the other APAP-treated groups received daily injections for 15 and 30 days. CSD was induced by the topical application of KCl to the parietal cortex. The protein expression of CGRP in the TG was evaluated by immunohistochemistry, and the CGRP mRNA level was investigated by real-time quantitative reverse transcription polymerase chain reaction. The results revealed that the induction of CSD significantly increased the level of CGRP protein but had no effect on CGRP mRNA level. Pretreatment with APAP 1 hour before CSD activation significantly reduced CGRP expression induced by CSD. In contrast, chronic treatment with APAP (15 and 30 days) significantly enhanced CGRP expression in both protein and mRNA levels when compared with the control groups. In combination with CSD, the expression of CGRP further increased in the animal with 30 day treatment. These findings indicate that chronic treatment with APAP induces an increase of CGRP expression in the TG. This alteration may be associated with the increased trigeminovascular nociception observed in our previous studies.
authors.affiliation: Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Waranurin
authors.initials: W
authors.lastname: Yisarakun
authors.affiliation: Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Chattraporn
authors.initials: C
authors.lastname: Chantong
authors.affiliation: Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Weera
authors.initials: W
authors.lastname: Supornsilpchai
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Thananya
authors.initials: T
authors.lastname: Thongtan
authors.affiliation: Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Anan
authors.initials: A
authors.lastname: Srikiatkhachorn
authors.affiliation: Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Preecha
authors.initials: P
authors.lastname: Reuangwechvorachai
authors.affiliation: Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: le.grand.maneesri.s@gmail.com.
authors.forename: Supang
authors.initials: S
authors.lastname: Maneesri-le Grand
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D013181:Cortical Spreading Depression / Q000187:drug effects*; D004195:Disease Models, Animal; D008297:Male; D008881:Migraine Disorders / Q000378:metabolism*; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012668:Trigeminal Ganglion / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000082:Acetaminophen; D015740:Calcitonin Gene-Related Peptide
keywords: Calcitonin gene-related peptide; Cortical spreading depression; Paracetamol; Trigeminal ganglion