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Hormone replacement therapy did not alleviate temporomandibular joint inflammatory pain in ovariectomized rats

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Abstract

This study had the aim of examining the relationships between variations in estrogen levels resulting from ovariectomy, and estrogen hormone replacement therapy (HRT) in rats subjected to an orofacial inflammatory pain model. Eighty adult female Wistar rats were initially divided into 2 groups: Sham or ovariectomy (OVX—D1). Seven days later (D7), the rats were subjected to an unilateral infiltration of Freund’s Complete Adjuvant (CFA) or saline solution into the right temporomandibular joint (TMJ). Then, rats received 17β-estradiol (28 µg/kg/day) or placebo for 21 days (D10–D31). Nociception was evaluated by the von Frey (VF) and the Hot Plate (HP) tests, and depressive-like behavior by the Forced Swimming (FS) test. On D32 all rats were euthanized and serum, hippocampus and brainstem were collected. The CFA groups presented a mechanical hyperalgesia until day 21 (p ≤ 0.05). No differences were observed among groups in the HP (p = 0.735), and in the immobility and swimming time of the FS (p = 0.800; p = 0.998, respectively). In the brainstem, there was a significant difference in the TNF-ɑ levels (p = 0.043), and a marginal significant difference in BDNF levels (p = 0.054), without differences among groups in the hippocampal BDNF and TNF-ɑ levels (p = 0.232; p = 0.081, respectively). In conclusion, the hormone replacement therapy did not alleviate orofacial pain in ovariectomized rats. However, there is a decrease in brainstem TNF-ɑ levels in the animals submitted to both models, which was partially reverted by HRT.

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Data availability

The data that support the findings of this study are available on request from the corresponding author (I.L.S.T).

References

  1. Tsang A, Von Korff M, Lee S, Alonso J, Karam E, Angermeyer MC, Borges GL, Bromet EJ, Demytteneare K, de Girolamo G, de Graaf R, Gureje O, Lepine JP, Haro JM, Levinson D, Oakley Browne MA, Posada-Villa J, Seedat S, Watanabe M. Common chronic pain conditions in developed and develo** countries: gender and age differences and comorbidity with depression-anxiety disorders. J Pain. 2008;9(10):883–91. https://doi.org/10.1016/j.jpain.2008.05.005.

    Article  PubMed  Google Scholar 

  2. Neville A, Peleg R, Singer Y, Sherf M, Shvartzman P. Chronic Pain: a population-based study. Isr Med Assoc J. 2008;10:676–80 (PMID:19009944).

    PubMed  Google Scholar 

  3. Unruh AM. Gender variations in clinical pain experience. Pain. 1996;65(2–3):123–67. https://doi.org/10.1016/0304-3959(95)00214-6. (PMID: 8826503).

    Article  CAS  PubMed  Google Scholar 

  4. Hornung RS, Raut NG, Cantu DJ, Lockhart LM, Averitt DL. Sigma-1 receptors and progesterone metabolizing enzymes in nociceptive sensory neurons of the female rat trigeminal ganglia: a neural substrate for the antinociceptive actions of progesterone. Mol Pain. 2022;18:17448069211069256. https://doi.org/10.1177/17448069211069255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hilgenberg PB, Cunha CO, Mendonça LM, Conti PCR. Dor orofacial odontogênica e a importância do diagnóstico diferencial. Relato de caso Rev Dor. 2010;11(2):169–72.

    Google Scholar 

  6. Ferneini EM. Temporomandibular Joint Disorders (TMD). J Oral Maxillofac Surg. 2021;79(10):2171–2. https://doi.org/10.1016/j.joms.2021.07.008. (PMID: 34620421).

    Article  PubMed  Google Scholar 

  7. Oliveira LK, Almeida Gde A, Lelis ÉR, Tavares M, Fernandes Neto AJ. Temporomandibular disorder and anxiety, quality of sleep, and quality of life in nursing professionals. Braz Oral Res. 2015;29:S1806-83242015000100270. https://doi.org/10.1590/1807-3107BOR-2015. (PMID: 26039910).

    Article  PubMed  Google Scholar 

  8. Demyttenaere K, Bruffaerts R, Lee S, Posada-Villa J, Kovess V, Angermeyer MC, Levinson D, de Girolamo G, Nakane H, Mneimneh Z, Lara C, de Graaf R, Scott KM, Gureje O, Stein DJ, Haro JM, Bromet EJ, Kessler RC, Alonso J, Von Korff M. Mental disorders among persons with chronic back or neck pain: results from the World Mental Health Surveys. Pain. 2007;129(3):332–42. https://doi.org/10.1016/j.pain.2007.01.022. (Epub 2007 Mar 9 PMID: 17350169).

    Article  PubMed  Google Scholar 

  9. Wang J, Chao Y, Wan Q, Zhu Z. The possible role of estrogen in the incidence of temporomandibular disorders. Med Hypotheses. 2008;71:564–7. https://doi.org/10.1016/j.mehy.2008.05.011. (Epub 2008 Jul 1 PMID: 18597950).

    Article  CAS  PubMed  Google Scholar 

  10. Albertin A, Kerppers II, Amorim CF, Costa RV, Ferrari Correa JC, Oliveira CS. The effect of manual therapy on masseter muscle pain and spasm. Electromyogr Clin Neurophysiol. 2010;50(2):107–12 (PMID: 20405786).

    CAS  PubMed  Google Scholar 

  11. Gomes NC, Berni-Schwarzenbeck KC, Packer AC, Rodrigues-Bigaton D. Effect of cathodal high-voltage electrical stimulation on pain in women with TMD. Rev Bras Fisioter. 2012;16(1):10–5.

    Article  PubMed  Google Scholar 

  12. Zhou FH, Zhao HY. Acupuncture and ultrasound therapy for temporomandibular disorders. Di Yi Jun Yi Da Xue Xue Bao. 2004;24(6):720–1 (Chinese PMID: 15201103).

    PubMed  Google Scholar 

  13. Rodrigues D, Siriani AO, Bérzin F. Effect of conventional TENS on pain and electromyographic activity of masticatory muscles in TMD patients. Braz Oral Res. 2004;18(4):290–5. https://doi.org/10.1590/s1806-83242004000400003.

    Article  PubMed  Google Scholar 

  14. Romero-Reyes M, Uyanik JM. Orofacial pain management: current perspectives. J Pain Res. 2014;21(7):99–115. https://doi.org/10.2147/JPR.S37593.

    Article  Google Scholar 

  15. LeResche L, Saunders K, Von Korff MR, Barlow W, Dworkin SF. Use of exogenous hormones and risk of temporomandibular disorder pain. Pain. 1997;69(1–2):153–60. https://doi.org/10.1016/s0304-3959(96)03230-7.

    Article  CAS  PubMed  Google Scholar 

  16. Figueroba SR, Franco GC, Omar NF, Groppo MF, Groppo FC. Dependence of cytokine levels on the sex of experimental animals: a pilot study on the effect of oestrogen in the temporomandibular joint synovial tissues. Int J Oral Maxillofac Surg. 2015;44(11):1368–75. https://doi.org/10.1016/j.ijom.2015.06.025. (Epub 2015 Jul 17 PMID: 26194775).

    Article  CAS  PubMed  Google Scholar 

  17. Abdrabuh A, Baljon K, Alyami Y. Impact of estrogen therapy on temporomandibular joints of rats: Histological and hormone analytical study. Saudi Dent J. 2021;33(7):608–13. https://doi.org/10.1016/j.sdentj.2020.07.006.

    Article  PubMed  Google Scholar 

  18. Berger M, Szalewski L, Bakalczuk M, Bakalczuk G, Bakalczuk S, Szkutnik J. Association between estrogen levels and temporomandibular disorders: a systematic literature review. Prz Menopauzalny. 2015;14(4):260–70. https://doi.org/10.5114/pm.2015.56538.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Fejes-Szabó A, Spekker E, Tar L, Nagy-Grócz G, Bohár Z, Laborc KF, Vécsei L, Párdutz Á. Chronic 17β-estradiol pretreatment has pronociceptive effect on behavioral and morphological changes induced by orofacial formalin in ovariectomized rats. J Pain Res. 2018;25(11):2011–21. https://doi.org/10.2147/JPR.S165969.

    Article  Google Scholar 

  20. Bagis B, Ayaz EA, Turgut S, Durkan R, Özcan M. Gender difference in prevalence of signs and symptoms of temporomandibular joint disorders: a retrospective study on 243 consecutive patients. Int J Med Sci. 2012;9(7):539–44. https://doi.org/10.7150/ijms.4474.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lora VR, Canales Gde L, Gonçalves LM, Meloto CB, Barbosa CM. Prevalence of temporomandibular disorders in postmenopausal women and relationship with pain and HRT. Braz Oral Res. 2016;30(1):e100. https://doi.org/10.1590/1807-3107BOR-2016.vol30.0100. (PMID: 27556676).

    Article  PubMed  Google Scholar 

  22. Nekora-Azak A, Evlioglu G, Ceyhan A, Keskin H, Berkman S, Issever H. Estrogen replacement therapy among postmenopausal women and its effects on signs and symptoms of temporomandibular disorders. Cranio. 2008;26(3):211–5. https://doi.org/10.1179/crn.2008.028. (PMID: 18686498).

    Article  PubMed  Google Scholar 

  23. Hatch JP, Rugh JD, Sakai S, Saunders MJ. Is use of exogenous estrogen associated with temporomandibular signs and symptoms? J Am Dent Assoc. 2001;132(3):319–26. https://doi.org/10.14219/jada.archive.2001.0174. (PMID: 11258088).

    Article  CAS  PubMed  Google Scholar 

  24. Harding AT, Heaton NS. The Impact of Estrogens and Their Receptors on Immunity and Inflammation during Infection. Cancers (Basel). 2022;14(4):909. https://doi.org/10.3390/cancers14040909.

    Article  CAS  PubMed  Google Scholar 

  25. Zwiri A, Al-Hatamleh MAI, Ahmad W, WMA, Ahmed Asif J, Khoo SP, Husein A, Ab-Ghani Z, Kassim NK. Biomarkers for temporomandibular disorders: current status and future directions. Diagnost (Basel). 2020;10(5):303. https://doi.org/10.3390/diagnostics10050303.

    Article  CAS  Google Scholar 

  26. Campos MIG, Campos PSF, Line SRP. 2015 Inflammatory cytokines activity in temporomandibular joint disorders: a review of literature. Braz J Oral Sci. 5:(18) 1054–62. Available from: https://periodicos.sbu.unicamp.br/ojs/index.php/bjos/article/view/8641896

  27. Schulte W, Bernhagen J, Bucala R. Cytokines in sepsis: potent immunoregulators and potential therapeutic targets–an updated view. Mediators Inflamm. 2013;2013:165974. https://doi.org/10.1155/2013/165974.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Davies AM. The role of neurotrophins in the develo** nervous system. J Neurobiol. 1994;25(11):1334–48. https://doi.org/10.1002/neu.480251103. (PMID: 7852989).

    Article  CAS  PubMed  Google Scholar 

  29. Bemelmans MH, van Tits LJ, Buurman WA. Tumor necrosis factor: function, release and clearance. Crit Rev Immunol. 1996;16(1):1–11. https://doi.org/10.1615/critrevimmunol.v16.i1.10. (PMID: 8809470).

    Article  CAS  PubMed  Google Scholar 

  30. Snider WD. Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell. 1994;77(5):627–38. https://doi.org/10.1016/0092-8674(94)90048-5. (PMID: 8205613).

    Article  PubMed  Google Scholar 

  31. Scharfman HE, MacLusky NJ. Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: complexity of steroid hormone-growth factor interactions in the adult CNS. Front Neuroendocrinol. 2006;27(4):415–35. https://doi.org/10.1016/j.yfrne.2006.09.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jasim H, Ghafouri B, Gerdle B, Hedenberg-Magnusson B, Ernberg M. Altered levels of salivary and plasma pain related markers in temporomandibular disorders. J Headache Pain. 2020;21:1.

    Article  Google Scholar 

  33. Fischer M, Wille G, Klien S, Shanib H, Holle D, Gaul C, et al. Brain-derived neurotrophic factor in primary headaches. J Headache Pain. 2012;13(6):469–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nijs J, Meeus M, Versijpt J, Moens M, Bos I, Knaepen K, et al. Brain-derived neurotrophic factor as a driving force behind neuroplasticity in neuropathic and central sensitization pain: a new therapeutic target? Expert Opin Ther Targets. 2015;19(4):565–76.

    Article  CAS  PubMed  Google Scholar 

  35. Simao AP, Mendonca VA, de Oliveira Almeida TM, Santos SA, Gomes WF, Coimbra CC, et al. Involvement of BDNF in knee osteoarthritis: the relationship with inflammation and clinical parameters. Rheumatol Int. 2014;34(8):1153–7.

    Article  CAS  PubMed  Google Scholar 

  36. Merighi A, Salio C, Ghirri A, Lossi L, Ferrini F, Betelli C, Bardoni R. BDNF as a pain modulator. Prog Neurobiol. 2008;85(3):297–317. https://doi.org/10.1016/j.pneurobio.2008.04.004. (Epub 2008 Apr 26 PMID: 18514997).

    Article  CAS  PubMed  Google Scholar 

  37. Binder DK, Scharfman HE. Brain-derived neurotrophic factor. Growth Factors. 2004;22(3):123–31. https://doi.org/10.1080/08977190410001723308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Park SB, Lee YJ, Chung CK. Bone mineral density changes after ovariectomy in rats as an osteopenic model: stepwise description of double dorso-lateral approach. J Korean Neurosurg Soc. 2010;48(4):309–12. https://doi.org/10.3340/jkns.2010.48.4.309.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Philippe L, Gegout-Pottie P, Guingamp C, Bordji K, Terlain B, Netter P, Gillet P. Relations between functional, inflammatory, and degenerative parameters during adjuvant arthritis in rats. Am J Physiol. 1997;273(4):R1550–6. https://doi.org/10.1152/ajpregu.1997.273.4.R1550. (PMID: 9362323).

    Article  CAS  PubMed  Google Scholar 

  40. Yamazaki Y, Ren K, Shimada M, Iwata K. Modulation of paratrigeminal nociceptive neurons following temporomandibular joint inflammation in rats. Exp Neurol. 2008;214(2):209–18. https://doi.org/10.1016/j.expneurol.2008.08.005.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Imbe H, Iwata K, Zhou QQ, Zou S, Dubner R, Ren K. Orofacial deep and cutaneous tissue inflammation and trigeminal neuronal activation implications for persistent temporomandibular pain. Cells Tissues Organs. 2001;169(3):238–47.

    Article  CAS  PubMed  Google Scholar 

  42. Ström JO, Theodorsson A, Ingberg E, Isaksson IM, Theodorsson E. Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration. J Vis Exp. 2012;64:e4013. https://doi.org/10.3791/4013.

    Article  CAS  Google Scholar 

  43. Goldman JM, Murr AS, Cooper RL. The rodent estrous cycle: characterization of vaginal cytology and its utility in toxicological studies. Birth Defects Res B Dev Reprod Toxicol. 2007;80(2):84–97. https://doi.org/10.1002/bdrb.20106. (PMID: 17342777).

    Article  CAS  PubMed  Google Scholar 

  44. Liu S, Crawford J, Tao F. Assessing orofacial pain behaviors in animal models: a review. Brain Sci. 2023;13(3):390. https://doi.org/10.3390/brainsci13030390.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Woolfe G, MacDonald AD. The evaluation of the analgesic action of pethidine hydrochloride. J Pharmacol Exp Ther. 1944;80(3):300–7.

    CAS  Google Scholar 

  46. Gregory NS, Harris AL, Robinson CR, Dougherty PM, Fuchs PN, Sluka KA. An overview of animal models of pain: disease models and outcome measures. J Pain. 2013;14(11):1255–69. https://doi.org/10.1016/j.jpain.2013.06.008.

    Article  PubMed  Google Scholar 

  47. Castagné V, Moser P, Roux S, Porsolt RD. Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice. Curr Protoc Pharmacol. 2010. https://doi.org/10.1002/0471141755.ph0508s49.

    Article  PubMed  Google Scholar 

  48. Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol. 1978;47(4):379–91. https://doi.org/10.1016/0014-2999(78)90118-8. (PMID: 204499).

    Article  CAS  PubMed  Google Scholar 

  49. Fillingim RB, Ness TJ. Sex-related hormonal influences on pain and analgesic responses. Neurosci Biobehav Rev. 2000;24(4):485–501. https://doi.org/10.1016/s0149-7634(00)00017-8. (PMID: 10817845).

    Article  CAS  PubMed  Google Scholar 

  50. Abdus-Saboor I, Fried NT, Lay M, Burdge J, Swanson K, Fischer R, Jones J, Dong P, Cai W, Guo X, Tao YX, Bethea J, Ma M, Dong X, Ding L, Luo W. Development of a mouse pain scale using sub-second behavioral map** and statistical modeling. Cell Rep. 2019;28(6):1623-1634e4. https://doi.org/10.1016/j.celrep.2019.07.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Okamoto K, Tashiro A, Hirata H, Bereiter DA. Differential modulation of TMJ neurons in superficial laminae of trigeminal subnucleus caudalis/upper cervical cord junction region of male and cycling female rats by morphine. Pain. 2005;114(1–2):203–11. https://doi.org/10.1016/j.pain.2004.12.013. (Epub 2005 Jan 26 PMID: 15733646).

    Article  CAS  PubMed  Google Scholar 

  52. da Silva Moreira SF, Medeiros LF, de Souza A, de Oliveira C, Scarabelot VL, Fregni F, Caumo W, Torres IL. Transcranial direct current stimulation (tDCS) neuromodulatory effects on mechanical hyperalgesia and cortical BDNF levels in ovariectomized rats. Life Sci. 2016;15(145):233–9. https://doi.org/10.1016/j.lfs.2015.10.011. (Epub 2015 Oct 22 PMID: 26471218).

    Article  CAS  Google Scholar 

  53. Paller CJ, Campbell CM, Edwards RR, Dobs AS. Sex-based differences in pain perception and treatment. Pain Med. 2009;10(2):289–99. https://doi.org/10.1111/j.1526-4637.2008.00558.x.

    Article  PubMed  Google Scholar 

  54. Chakraborty TR, Gore AC. Aging-related changes in ovarian hormones, their receptors, and neuroendocrine function. Exp Biol Med (Maywood). 2004;229(10):977–87. https://doi.org/10.1177/153537020422901001. (PMID: 15522833).

    Article  CAS  PubMed  Google Scholar 

  55. Hwang C, Pu HF, Hwang CY, Liu JY, Yao HC, Tung YF, Wang PS. Age-related differences in the release of luteinizing hormone and gonadotropin-releasing hormone in ovariectomized rats. Neuroendocrinology. 1990;52(2):127–32. https://doi.org/10.1159/000125562. (PMID: 2125700).

    Article  CAS  PubMed  Google Scholar 

  56. Borsini F, Meli A. Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology. 1988;94(2):147–60. https://doi.org/10.1007/BF00176837. (PMID: 3127840).

    Article  CAS  PubMed  Google Scholar 

  57. Li LH, Wang ZC, Yu J, Zhang YQ. Ovariectomy results in variable changes in nociception, mood and depression in adult female rats. PLoS ONE. 2014;9(4):e94312. https://doi.org/10.1371/journal.pone.0094312.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Walf AA, Paris JJ, Frye CA. Chronic estradiol replacement to aged female rats reduces anxiety-like and depression-like behavior and enhances cognitive performance. Psychoneuroendocrinology. 2009;34(6):909–16. https://doi.org/10.1016/j.psyneuen.2009.01.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Grigoryan GA. Ovariectomy as a model of anxiety-depressive disorders. Neurochem J. 2022;16:1–13. https://doi.org/10.1134/S1819712422010068.

    Article  CAS  Google Scholar 

  60. Kiss A, Delattre AM, Pereira SI, Carolino RG, Szawka RE, Anselmo-Franci JA, Zanata SM, Ferraz AC. 17β-estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas. Behav Brain Res. 2012;227(1):100–8. https://doi.org/10.1016/j.bbr.2011.10.047. (Epub 2011 Nov 7 PMID: 22085882).

    Article  CAS  PubMed  Google Scholar 

  61. Boivin JR, Piekarski DJ, Wahlberg JK, Wilbrecht L. Age, sex, and gonadal hormones differently influence anxiety- and depression-related behavior during puberty in mice. Psychoneuroendocrinology. 2017;85:78–87. https://doi.org/10.1016/j.psyneuen.2017.08.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. do Nascimento GC, Leite-Panissi CR. Time-dependent analysis of nociception and anxiety-like behavior in rats submitted to persistent inflammation of the temporomandibular joint. Physiol Behav. 2014;125:1–7. https://doi.org/10.1016/j.physbeh.2013.11.009.

    Article  CAS  PubMed  Google Scholar 

  63. Spears R, Dees LA, Sapozhnikov M, Bellinger LL, Hutchins B. Temporal changes in inflammatory mediator concentrations in an adjuvant model of temporomandibular joint inflammation. J Orofac Pain. 2005;19(1):34–40.

    PubMed  Google Scholar 

  64. Rauf A, Badoni H, Abu-Izneid T, Olatunde A, Rahman MM, Painuli S, Semwal P, Wilairatana P, Mubarak MS. Neuroinflammatory markers: key indicators in the pathology of neurodegenerative diseases. Molecules. 2022;27(10):3194. https://doi.org/10.3390/molecules27103194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Beyeler SA, Naidoo R, Plunkett DLM, Huxtable AG. Homotypic neonatal and adult inflammation primes adult microglia without impairing adult breathing. The Faseb J: Physiol. 2022. https://doi.org/10.1096/fasebj.2022.36.S1.0R587.

    Article  Google Scholar 

  66. Chung JY, Yi JW, Kim SM, Lim YJ, Chung JH, Jo DJ. Changes in gene expression in the rat hippocampus after focal cerebral ischemia. J Korean Neurosurg Soc. 2011;50(3):173–8. https://doi.org/10.3340/jkns.2011.50.3.173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Hedley KE, Callister RJ, Callister R, Horvat JC, Tadros MA. Alterations in brainstem respiratory centers following peripheral inflammation: a systematic review. J Neuroimmunol. 2022;369:577903. https://doi.org/10.1016/j.jneuroim.2022.577903.

    Article  CAS  PubMed  Google Scholar 

  68. Kraynak TE, Marsland AL, Wager TD, Gianaros PJ. Functional neuroanatomy of peripheral inflammatory physiology: a meta-analysis of human neuroimaging studies. Neurosci Biobehav Rev. 2018;94:76–92. https://doi.org/10.1016/j.neubiorev.2018.07.013.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Basinger H, Hogg JP. Neuroanatomy, Brainstem. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544297/

  70. Smith PA. BDNF: no gain without pain? Neuroscience. 2014;26(283):107–23. https://doi.org/10.1016/j.neuroscience.2014.05.044. (Epub 2014 Jun 2 PMID: 24887639).

    Article  CAS  Google Scholar 

  71. Russell WMS, Burch RL. The principles of humane experimental technique, Methuen, London. ISBN 0900767782. 1959. https://caat.jhsph.edu/the-principles-of-humane-experimental-technique/

  72. Muley MM, Krustev E, McDougall JJ. Preclinical assessment of inflammatory pain. CNS Neurosci Ther. 2016;22(2):88–101. https://doi.org/10.1111/cns.12486.

    Article  PubMed  Google Scholar 

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Funding

This study was supported by the following Brazilian funding agencies: the National Council for Scientific and Technological Development, CNPq for research grants (I.L.S.T.: PQ #302345/2011–6; WC: PQ #301256/2013–6); Research Incentive Fund at the Hospital de Clínicas de Porto Alegre (FIPE/HCPA) and Graduate and Research Group at the Hospital de Clínicas de Porto Alegre, GPPG/HCPA (I.L.S. Torres – FIPE HCPA Grant #2021–0632). Brazilian Federal Agency for Support and Evaluation of Graduate Education, CAPES (J.M. de Castro, Dr. D.J. Stein); (V) Brazilian Innovation Agency (FINEP) (WC and ILST process #1245/13).

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All authors contributed substantially to the present work. Giovana Paola Heck Kroeff: Conceptualization, Investigation, Methodology, Formal analysis, Data curation, Visualization, Writing—Original Draft; Writing—Review & Editing; Josimar Macedo de Castro: Investigation, Data Curation, Formal analysis, Writing—Review and Editing; Hemily Barbosa Braga: Investigation; Tenille Dal Bosco: Investigation; Thais Collioni de Oliveira: Investigation; Iala Thais de Sousa Morais: Investigation; Liciane F Medeiros: Investigation, Methodology; Wolnei Caumo: Resources, Writing—Review and Editing; Dirson J Stein: Supervision, Investigation, Methodology, Visualization, Writing—Review and Editing; Iraci LS Torres: Supervision, Project administration, Funding acquisition, Writing—Review & Editing;

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Correspondence to Iraci L. S. Torres.

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Kroeff, G.P.H., de Castro, J.M., Braga, H.B. et al. Hormone replacement therapy did not alleviate temporomandibular joint inflammatory pain in ovariectomized rats. Odontology (2024). https://doi.org/10.1007/s10266-024-00964-8

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