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Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (1): 40-47. doi: 10.19723/j.issn.1671-167X.2022.01.007

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Hippocampus is involved in 17β-estradiol exacerbating experimental occlusal inter-ference-induced chronic masseter hyperalgesia in ovariectomized rats

FAN Ying-ying,LIU Yun,CAO Ye(),XIE Qiu-fei()   

  1. Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & NHC Research Center of Engineering and Technology for Computerized Dentistry & NMPA Key Laboratory for Dental Materials, Beijing 100081, China
  • Received:2021-10-09 Online:2022-02-18 Published:2022-02-21
  • Contact: Ye CAO,Qiu-fei XIE E-mail:ye.cao@bjmu.edu.cn;xieqiuf@163.com
  • Supported by:
    National Natural Science Foundation of China(81771096)

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Abstract:

Objective: To investigate the influence of chronic masseter hyperalgesia induced by 17β-estradiol (E2) and experimental occlusal interference (EOI) on underlying mechanism in hippocampus of ovariectomized (OVX) rats. Methods: In the study, 32 OVX rats were randomly divided into 4 groups (8 rats/group): The control group was OVX group, and 0 μg/d E2 (vehicle) injection was started 7 d after OVX without EOI; in the experimental group (1) OVX + E2 group, 80 μg/d E2 injection was started 7 d after OVX without EOI; in the experimental group (2) OVX + EOI group, vehicle injection was started 7 d after OVX and EOI was applied 17 d after OVX; in the experimental group (3) OVX + E2 + EOI group, 80 μg/d E2 injection was started 7 d after OVX and EOI was applied 17 d after OVX. Bilateral masseter muscle mechanical withdrawal thresholds were measured before OVX, 7 days after OVX (before E2 injection), 17 days after OVX (10 days after E2 injection and before EOI) and 24 days after OVX (7 days after EOI). Immunofluorescence staining was used to reveal phospho-extracellular signal regulated kinase 1/2 (p-ERK1/2)-positive neurons in CA3 of hippocampus. The protein expression of p-ERK1/2 in hippocampus was detected using Western Blot. Results: Compared with the control group [left side: (135.3±8.5) g, right side: (135.4±10.8) g], bilateral masseter muscle mechanical withdrawal thresholds of OVX+E2 group [left side: (113.3±5.6) g, right side: (112.5 ± 5.6) g] and OVX+EOI group [left side: (93.3±5.4) g, right side: 90.8±5.5) g] were decreased (P<0.01). Bilateral masseter muscle mechanical withdrawal thresholds were significantly lower in OVX+E2+EOI group [left side: (81.2±6.2) g, right side: 79.8±7.7) g] than in the control, OVX+E2 and OVX+EOI groups (P<0.05). The proportion of p-ERK1/2 positive neurons in the CA3 region of the hippocampus was increased in the control, OVX+E2, OVX+EOI and OVX+E2+EOI groups in turn, and the difference between the groups was statistically significant (P<0.05). p-ERK1/2 protein expression was increased in the control, OVX+E2 and OVX+EOI groups in turn, but the difference was not statistically significant (P>0.05). p-ERK1/2 expression was significantly higher in OVX+E2+EOI group than in the other three groups (P<0.05). Conclusion: High concentration of E2 could exacerbated EOI-induced chronic masseter hyperalgesia in ovariectomized rats, and its central mechanism may be related to the upregulation of the phosphorylation of ERK1/2 in hippocampus.

Key words: 17β-estradiol, Occlusal interference, Hippocampus, Masseter hyperalgesia, Phospho-extracellular signal regulated kinase 1/2

CLC Number: 

  • R781.6

Figure 1

Experimental flow chart OVX, ovariectomy; EOI, experimental occlusal interference; E2, 17β-estradiol; the day of OVX was taken as day 0."

Table 1

Comparison of head withdrawal threshold (HWT) between left and right bilateral masseters in each group (n=8)"

Items Baseline Day 7 (OVX 7 d) Day 17 (E2 10 d) Day 24 (EOI 7 d)
HWT/g, $\bar{x}\pm s$ P HWT/g, $\bar{x}\pm s$ P HWT/g, $\bar{x}\pm s$ P HWT/g, $\bar{x}\pm s$ P
OVX Left 115.9±4.4 0.108 140.3±7.8 0.701 142.9±4.9 0.127 135.3±8.5 0.959
Right 120.5±6.5 139.5±8.9 145.1±7.1 135.4±10.8
OVX + E2 Left 126.1±10.5 0.652 146.7±7.0 0.245 112.2±2.8 0.685 113.3±5.6 0.574
Right 124.9±13.1 143.4±8.0 111.5±5.3 112.5±5.6
OVX + EOI Left 123.5±5.5 0.073 141.6±5.0 0.238 136.5±5.7 0.325 93.3±5.4 0.235
Right 119.2±3.6 144.3±5.0 139.2±8.8 90.8±5.5
OVX + E2 + EOI Left 124.0±10.7 0.739 141.9±8.0 0.908 111.8±6.8 0.490 81.2±6.2 0.330
Right 125.1±6.8 142.4±6.8 114.5±8.8 79.8±7.7

Figure 2

Colocalization of p-ERK1/2 with NeuN in CA3 of the left hippocampus at day 24 (day 7 following placement of occlusal interference, n=3, immunofluorescence microscopy) OVX, ovariectomy; EOI, experimental occlusal interference; E2, 17β-estradiol; p-ERK1/2, phospho-extracellular signal regulated kinase1/2. The arrows indicate p-ERK1/2 (red) and NeuN (green) double-labeled neurons. * P<0.05, OVX compares with the other three groups;# P<0.05,OVX+E2 compares with the other three groups;△ P<0.05,OVX+EOI compares with the other three groups;▲ P<0.05,OVX+E2+EOI compares with the other three groups."

Figure 3

Colocalization of p-ERK1/2 with NeuN in CA3 of the right hippocampus at day 24 (day 7 following placement of occlusal interference, n=3, immunofluorescence microscopy) OVX, ovariectomy; EOI, experimental occlusal interference; E2, 17β-estradiol; p-ERK1/2, phospho-extracellular signal regulated kinase1/2. The arrows indicate p-ERK1/2 (red) and NeuN (green) double-labeled neurons. * P<0.05, OVX compares with the other three groups;# P<0.05,OVX+E2 compares with the other three groups;△ P<0.05,OVX+EOI compares with the other three groups;▲ P<0.05,OVX+E2+EOI compares with the other three groups."

Figure 4

Change of p-ERK1/2 level in hippocampus at day 24 (day 7 following placement of occlusal interference, n=5) * P<0.05; OVX, ovariectomy; EOI, experimental occlusal interference; E2, 17β-estradiol; p-ERK1/2, phospho-extracellular signal regulated kinase1/2; ERK1/2, extracellular signal regulated kinase1/2; GAPDH, glyceraldehyde 3-phosphate ehydrogenase."

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