Corticotropin releasing factor receptor 2 involves in pain sensitization and anxiety of chronic migraine mice
10.3760/cma.j.cn115354-20231022-00178
- VernacularTitle:促肾上腺皮质激素释放因子2型受体参与慢性偏头痛小鼠痛觉敏化及焦虑的机制研究
- Author:
Luhong ZOU
1
;
Chunhong YAN
;
Lingzhi WU
;
Xuejuan ZHANG
;
Jiang BIAN
Author Information
1. 攀枝花市中心医院麻醉科，攀枝花 617000
- Keywords:
Chronic migraine;
Corticotropin releasing factor;
Trigeminal nucleus caudalis;
Pain sensitization;
Anxiety
- From:
Chinese Journal of Neuromedicine
2024;23(2):131-139
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of corticotrophin releasing factor receptor 2 (CRFR2) in regulating pain sensitization and anxiety and its mechanism in chronic migraine mice.Methods:Forty-eight C57BL/6J mice were randomly divided into control group, model group, NBI35965 group and K41498 group ( n=12); chronic migraine models in the later 3 groups were established by intraperitoneally administrating 10 mg/kg nitroglycerin on the 1 st, 3 rd, 5 th, 7 th and 9 th d; mice in the NBI35965 group and K41498 group were injected with 100 nL NBI35965 or K41498 solution into the bilateral trigeminal nucleus caudalis on the 2 nd, 4 th, 6 th and 8 th d, and mice in the control group were injected with same volume of normal saline. Von frey fiber was used to detect the orbitofrontal mechanical pain threshold 2 h after intraperitoneal injection on the 1 st, 3 rd, 5 th, 7 th and 9 th d, and at 11 a.m. on the 10 th d. Elevated plus maze was used to detect the anxiety-like behaviors at 11 a.m. on the 11 th d. Western blotting was performed to detect the protein expressions of corticotrophin releasing factor (CRF), corticotrophin releasing factor receptor 1 (CRFR1), CRFR2 in the trigeminal nucleus caudalis. Real-time quantitative PCR (RT-qPCR) was used to detect the CRFR1 and CRFR2 mRNA expressions in the trigeminal nucleus caudalis. Immunofluorescent staining was used to detect the protein expressions of calcitonin gene-related peptide (CGRP), immediate-early gene c-fos, glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1) in the trigeminal nucleus caudalis. Results:Compared with the control group, the model group, NBI35965 group and K41498 group had significantly decreased orbitofrontal mechanical pain thresholds 3, 5, 7, 9, and 10 d after intraperitoneal injection ( P<0.05); compared with model group, the K41498 group had significantly increased orbitofrontal mechanical pain thresholds 7, 9, and 10 d after intraperitoneal injection ( P<0.05). Compared with control group, the model group, NBI35965 group and K41498 group had significantly decreased entries and shorter time in opened arms ( P<0.05); compared with the model group, the K41498 group had significantly increased entries and shorter time in opened arms ( P<0.05). Compared with the control group, the model group, NBI35965 group and K41498 group had significantly higher CRF and CRFR2 protein expressions in the trigeminal nucleus caudalis ( P<0.05); compared with the model group, the K41498 group had statistically lower CRF protein expression in the trigeminal nucleus caudalis ( P<0.05). Compared with the control group, the model group, NBI35965 group and K41498 group had significantly higher CRFR2 mRNA expression in the trigeminal nucleus caudalis ( P<0.05). Compard with the control group, the model group, NBI35965 group and K41498 group had significantly increased CGRP, c-fos, Iba-1 and GFAP protein expressions in the trigeminal nucleus caudalis ( P<0.05); compared with the model group, the K41498 group had significantly decreased CGRP and c-fos protein expressions in the trigeminal nucleus caudalis ( P<0.05). Conclusion:CRFR2 can alter the orbitofrontal pain sensitization and anxiety-like behaviors in chronic migraine mice by regulating neuronal activation and CGRP release in the trigeminal nucleus caudalis.
