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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."

[1] Cao Y. Occlusal disharmony and chronic oro-facial pain: from clinical observation to animal study[J]. J Oral Rehabil, 2021, 7 (2021-07-17) [2021-09-19]. https://onlinelibrary.wiley.com/doi/epdf/10.1111/joor.13236 .
[2] Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon[J]. Nat Rev Neuro-sci, 2012, 13(12):859-866.
[3] Cairns BE. The influence of gender and sex steroids on craniofacial nociception[J]. Headache, 2007, 47(2):319-324.
pmid: 17300382
[4] Bueno CH, Pereira DD, Pattussi MP, et al. Gender differences in temporomandibular disorders in adult populational studies: a systematic review and meta-analysis[J]. J Oral Rehabil, 2018, 45(9):720-729.
doi: 10.1111/joor.12661 pmid: 29851110
[5] Slade GD, Bair E, By K, et al. Study methods, recruitment, sociodemographic findings, and demographic representativeness in the OPPERA study[J]. J Pain, 2011, 12(11):12-26.
[6] Castrillon EE, Cairns BE, Wang K, et al. Comparison of glutamate-evoked pain between the temporalis and masseter muscles in men and women[J]. Pain, 2012, 153(4):823-829.
doi: 10.1016/j.pain.2012.01.003 pmid: 22336721
[7] Cao Y, Xie QF, Li K, et al. Experimental occlusal interference induces long-term masticatory muscle hyperalgesia in rats[J]. Pain, 2009, 144(3):287-293.
doi: 10.1016/j.pain.2009.04.029 pmid: 19473767
[8] Liu Y, Zhang XY, Fan YY, et al. Genistein reverses the effect of 17β-estradiol on exacerbating experimental occlusal interference-induced chronic masseter hyperalgesia in ovariectomised rats[J]. J Oral Rehabil, 2021, 2021, 6 (2021-06-02) [2021-09-19]. .
[9] Niu K, Saloman JL, Zhang Y, et al. Sex differences in the contribution of ATP-sensitive K(+) channels in trigeminal ganglia under an acute muscle pain condition[J]. Neuroscience, 2011, 1809(4):344-352.
[10] Cairns BE, Hu JW, Arendt-Nielsen L, et al. Sex-related differences in human pain and rat afferent discharge evoked by injection of glutamate into the masseter muscle[J]. J Neurophysiol, 2001, 86(2):782-791.
pmid: 11495950
[11] Wood PB, Ledbetter CR, Glabus MF, et al. Hippocampal meta-bolite abnormalities in fibromyalgia: correlation with clinical features[J]. J Pain, 2009, 10(1):47-52.
doi: 10.1016/j.jpain.2008.07.003
[12] Shimo K, Ueno T, Younger J, et al. Visualization of painful experiences believed to trigger the activation of affective and emotional brain regions in subjects with low back pain[J]. PLoS One, 2011, 6(11):1-6.
[13] Sakiyama Y, Sato A, Senda M, et al. Positron emission tomography reveals changes in global and regional cerebral blood flow during noxious stimulation of normal and inflamed elbow joints in anesthetized cats[J]. Exp Brain Res, 1998, 118(4):439-446.
doi: 10.1007/s002210050300
[14] Derbyshire SWG, Jones AKP, Gyulai F, et al. Pain processing during three levels of noxious stimulation produces differential patterns of central activity[J]. Pain, 1997, 73(3):431-445.
pmid: 9469535
[15] Aloisi AM, Zimmermann M, Herdegen T. Sex-dependent effects of formalin and restraint on c-Fos expression in the septum and hippocampus of the rat[J]. Neuroscience, 1997, 81(4):951-958.
pmid: 9330358
[16] Jia M, Dahlman-Wright K, Gustafsson JÅ. Estrogen receptor alpha and beta in health and disease[J]. Best Pract Res Clin Endocrinol Metab, 2015, 29(4):557-568.
doi: 10.1016/j.beem.2015.04.008
[17] Warfvinge K, Krause DN, Maddahi A, et al. Estrogen receptors α, β and GPER in the CNS and trigeminal system-molecular and functional aspects[J]. J Headache Pain, 2020, 21(1):131.
doi: 10.1186/s10194-020-01197-0
[18] Prange-Kiel J, Rune GM. Direct and indirect effects of estrogen on rat hippocampus[J]. Neuroscience, 2006, 138(3):765-772.
pmid: 16324798
[19] Henderson LA, Gandevia SC, Macefield VG. Gender differences in brain activity evoked by muscle and cutaneous pain: A retrospective study of single-trial fMRI data[J]. Neuroimage, 2008, 39(4):1867-1876.
pmid: 18069004
[20] Hubbard CS, Karpowicz JM, Furman AJ, et al. Estrogen-depen-dent visceral hypersensitivity following stress in rats: an fMRI study[J]. Mol Pain, 2016, 12:1-10.
[21] Jie HF, Yang GJ, Bi RY, et al. Genistein antagonizes 17β-estradiol effects on glutamate-evoked masseter muscle hypernociception in rats[J]. Front Neurol, 2018, 9:649.
doi: 10.3389/fneur.2018.00649
[22] Liverman CS, Brown JW, Sandhir R, et al. Oestrogen increases nociception through ERK activation in the trigeminal ganglion: evidence for a peripheral mechanism of allodynia[J]. Cephalal-gia, 2009, 29(5):520-531.
[23] Ji RR, Kohno T, Moore KA, et al. Central sensitization and LTP: do pain and memory share similar mechanisms?[J]. Trends Neurosci, 2003, 26(12):696-705.
doi: 10.1016/j.tins.2003.09.017
[24] Martuscello RT, Spengler RN, Bonoiu AC, et al. Increasing TNF levels solely in the rat hippocampus produces persistent pain-like symptoms[J]. Pain, 2012, 153(9):1871-1882.
doi: 10.1016/j.pain.2012.05.028 pmid: 22770843
[25] Ding TT, Xu XX, Cao Y, et al. Inflammatory pain memory facilitates occlusal interference-induced masticatory muscle hyperalgesia in rats[J]. Eur J Pain, 2016, 20(3):353-364.
doi: 10.1002/ejp.730 pmid: 26014463
[26] Gurtskaia G, Tsiklauri N, Nozadze I, et al. Antinociceptive tolerance to NSAIDs microinjected into dorsal hippocampus[J]. BMC Pharmacol Toxicol, 2014, 15(1):10.
doi: 10.1186/2050-6511-15-10
[27] Mckenna JE, Melzack R. Blocking NMDA receptors in the hippocampal dentate gyrus with AP5 produces analgesia in the formalin pain test[J]. Exp Neurol, 2001, 172(1):92-99.
doi: 10.1006/exnr.2001.7777
[28] Gol A, Faibish GM. Effects of human hippocampal ablation[J]. J Neurosurg, 1967, 26(4):390.
pmid: 6021342
[29] Liu Y, Xu XX, Cao Y, et al. 17β-Estradiol exacerbated experimental occlusal interference-induced chronic masseter hyperalgesia by increasing the neuronal excitability and TRPV1 function of trigeminal ganglion in ovariectomized rats[J]. Int J Mol Sci, 2021, 22(13):6945.
doi: 10.3390/ijms22136945
[30] Bi RY, Meng Z, Zhang P, et al. Estradiol upregulates voltage-gated sodium channel 1.7 in trigeminal ganglion contributing to hyperalgesia of inflamed TM[J]. PLoS One, 2017, 12(6):1-19.
[31] Payrits M, Sághy é, Cseko K, et al. Estradiol sensitizes the transient receptor potential vanilloid 1 receptor in pain responses[J]. Endocrinology, 2017, 158(10):3249-3258.
doi: 10.1210/en.2017-00101 pmid: 28977586
[32] 徐啸翔, 曹烨, 傅开元, 等. 咬合干扰致大鼠咬肌能量代谢产物含量变化[J]. 北京大学学报(医学版), 2017, 49(1):25-30.
[33] 徐啸翔, 曹烨, 丁婷婷, 等. 三叉神经节嘌呤能P2X4受体参与牙合干扰致大鼠咬肌痛觉过敏的研究[J]. 中华口腔医学杂志, 2016, 51(3):176-181.
[34] Xu XX, Cao Y, Ding TT, et al. Role of TRPV1 and ASIC3 channels in experimental occlusal interference-induced hyperalgesia in rat masseter muscle[J]. Eur J Pain, 2016, 20(4):552-563.
doi: 10.1002/ejp.758 pmid: 26201614
[35] Chen Y, Chen AQ, Luo XQ, et al. Hippocampal NR2B-containing NMDA receptors enhance long-term potentiation in rats with chronic visceral pain[J]. Brain Res, 2014, 1570:43-53.
doi: 10.1016/j.brainres.2014.05.001 pmid: 24824341
[36] Simonic-Kocijan S, Zhao X, Liu W, et al. TRPV1 channel-mediated bilateral allodynia induced by unilateral masseter muscle inflammation in rats[J]. Mol Pain, 2013, 9(1):68.
[37] Kim MT, Soussou W, Gholmieh G, et al. 17beta-Estradiol potentiates field excitatory postsynaptic potentials within each subfield of the hippocampus with greatest potentiation of the associational/commissural afferents of CA3[J]. Neuroscience, 2006, 141(1):391.
pmid: 16725270
[38] 贾静. 大鼠三叉神经脊束核和海马星形胶质细胞对咬合创伤的反应[D]. 北京, 中国人民解放军军医进修学院, 2005.
[39] Wu YW, Kou XX, Bi RY, et al. Hippocampal nerve growth factor potentiated by 17β-estradiol and involved in allodynia of inflamed TMJ in rat[J]. J Pain, 2012, 13(6):555-563.
doi: 10.1016/j.jpain.2012.03.005
[40] Leresche L, Saunders K, von Korff MR, et al. Use of exogenous hormones and risk of temporomandibular disorder pain[J]. Pain, 1997, 69(1/2):153-160.
doi: 10.1016/S0304-3959(96)03230-7
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