Chronic 17β-estradiol Pretreatment Has Pronociceptive Effect on Behavioral and Morphological Changes Induced by Orofacial Formalin in Ovariectomized Rats

Overview

Journal J Pain Res

Publisher Dove Medical Press

Date 2018 Oct 13

PMID 30310305

Citations 4

Authors

Annamaria Fejes-Szabo

Eleonora Spekker

Lilla Tar

Gabor Nagy-Grocz

Zsuzsanna Bohar

Klaudia Flora Laborc

Laszlo Vecsei

Arpad Pardutz

Affiliations

Soon will be listed here.

Abstract

Background: The prevalence of craniofacial pain disorders show sexual dimorphism with generally more common appearance in women suggesting the influence of estradiol, but the exact cause remains unknown. The common point in the pathogenesis of these disorders is the activation of trigeminal system. One of the animal experimental models of trigeminal activation is the orofacial formalin test, in which we investigated the effect of chronic 17β-estradiol pretreatment on the trigeminal pain-related behavior and activation of trigeminal second-order neurons at the level of spinal trigeminal nucleus pars caudalis (TNC).

Methods: Female Sprague Dawley rats were ovariectomized and silicone capsules were implanted subcutaneously containing cholesterol in the OVX group and 17β-estradiol and cholesterol in 1:1 ratio in the OVX+E group. We determined 17β-estradiol levels in serum after the implantation of capsules. Three weeks after operation, 50 µL of physiological saline or 1.5% of formalin solution was injected subcutaneously into the right whisker pad of rats. The time spent on rubbing directed to the injected area and c-Fos immunoreactivity in TNC was measured as the formalin-induced pain-related behavior, and as the marker of pain-related neuronal activation, respectively.

Results: The chronic 17β-estradiol pretreatment mimics the plasma levels of estrogen occurring in the proestrus phase and significantly increased the formalin-induced pain-related behavior and neuronal activation in TNC.

Conclusion: Our results demonstrate that the chronic 17β-estradiol treatment has strong pronociceptive effect on orofacial formalin-induced inflammatory pain suggesting modulatory action of estradiol on head pain through estrogen receptors, which are present in the trigeminal system.

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References

Tashiro A, Okamoto K, Bereiter D . Chronic inflammation and estradiol interact through MAPK activation to affect TMJ nociceptive processing by trigeminal caudalis neurons. Neuroscience. 2009; 164(4):1813-20. PMC: 2813765. DOI: 10.1016/j.neuroscience.2009.09.058. View

Flores C, Shughrue P, Petersen S, Mokha S . Sex-related differences in the distribution of opioid receptor-like 1 receptor mRNA and colocalization with estrogen receptor mRNA in neurons of the spinal trigeminal nucleus caudalis in the rat. Neuroscience. 2003; 118(3):769-78. DOI: 10.1016/s0306-4522(02)01000-x. View

Cairns B . The influence of gender and sex steroids on craniofacial nociception. Headache. 2007; 47(2):319-24. DOI: 10.1111/j.1526-4610.2006.00708.x. View

Lipton R, Stewart W, Diamond S, Diamond M, Reed M . Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001; 41(7):646-57. DOI: 10.1046/j.1526-4610.2001.041007646.x. View

Puri V, Puri S, Svojanovsky S, Mathur S, MacGregor R, Klein R . Effects of oestrogen on trigeminal ganglia in culture: implications for hormonal effects on migraine. Cephalalgia. 2006; 26(1):33-42. DOI: 10.1111/j.1468-2982.2005.00987.x. View

Somerville B . Estrogen-withdrawal migraine. I. Duration of exposure required and attempted prophylaxis by premenstrual estrogen administration. Neurology. 1975; 25(3):239-44. DOI: 10.1212/wnl.25.3.239. View

Amandusson A, Blomqvist A . Estrogen receptor-alpha expression in nociceptive-responsive neurons in the medullary dorsal horn of the female rat. Eur J Pain. 2009; 14(3):245-8. DOI: 10.1016/j.ejpain.2009.05.008. View

Srivastava D, Woolfrey K, Penzes P . Insights into rapid modulation of neuroplasticity by brain estrogens. Pharmacol Rev. 2013; 65(4):1318-50. PMC: 3799233. DOI: 10.1124/pr.111.005272. View

Gazerani P, Dong X, Wang M, Kumar U, Cairns B . Sensitization of rat facial cutaneous mechanoreceptors by activation of peripheral N-methyl-d-aspartate receptors. Brain Res. 2010; 1319:70-82. DOI: 10.1016/j.brainres.2010.01.018. View

10.

Niu K, Zhang Y, Ro J . Effects of gonadal hormones on the peripheral cannabinoid receptor 1 (CB1R) system under a myositis condition in rats. Pain. 2012; 153(11):2283-2291. PMC: 3578305. DOI: 10.1016/j.pain.2012.07.037. View

11.

Hazell G, Yao S, Roper J, Prossnitz E, OCarroll A, Lolait S . Localisation of GPR30, a novel G protein-coupled oestrogen receptor, suggests multiple functions in rodent brain and peripheral tissues. J Endocrinol. 2009; 202(2):223-36. PMC: 2710976. DOI: 10.1677/JOE-09-0066. View

12.

Liverman C, Brown J, Sandhir R, Klein R, McCarson K, Berman N . Oestrogen increases nociception through ERK activation in the trigeminal ganglion: evidence for a peripheral mechanism of allodynia. Cephalalgia. 2009; 29(5):520-31. PMC: 2671577. DOI: 10.1111/j.1468-2982.2008.01755.x. View

13.

Nag S, Mokha S . Activation of alpha2-adrenoceptors in the trigeminal region produces sex-specific modulation of nociception in the rat. Neuroscience. 2006; 142(4):1255-62. DOI: 10.1016/j.neuroscience.2006.07.012. View

14.

Lee K, Asgar J, Zhang Y, Chung M, Ro J . The role of androgen receptor in transcriptional modulation of cannabinoid receptor type 1 gene in rat trigeminal ganglia. Neuroscience. 2013; 254:395-403. PMC: 3870904. DOI: 10.1016/j.neuroscience.2013.09.014. View

15.

Tashiro A, Okamoto K, Bereiter D . Rapid estrogenic effects on TMJ-responsive brainstem neurons. J Dent Res. 2011; 91(2):210-4. PMC: 3261121. DOI: 10.1177/0022034511428156. View

16.

Liverman C, Brown J, Sandhir R, McCarson K, Berman N . Role of the oestrogen receptors GPR30 and ERalpha in peripheral sensitization: relevance to trigeminal pain disorders in women. Cephalalgia. 2009; 29(7):729-41. PMC: 4054707. DOI: 10.1111/j.1468-2982.2008.01789.x. View

17.

Gupta S, McCarson K, Welch K, Berman N . Mechanisms of pain modulation by sex hormones in migraine. Headache. 2011; 51(6):905-22. DOI: 10.1111/j.1526-4610.2011.01908.x. View

18.

Wise E, Price D, Myers C, Heft M, Robinson M . Gender role expectations of pain: relationship to experimental pain perception. Pain. 2002; 96(3):335-342. PMC: 2535906. DOI: 10.1016/S0304-3959(01)00473-0. View

19.

Yu L, Li N, Liu C, Ma B . Estrogen altered facial mechanical pain threshold and trigeminal P2X3 receptor expression. Neuro Endocrinol Lett. 2012; 32(6):811-5. View

20.

Pajot J, Ressot C, Ngom I, Woda A . Gonadectomy induces site-specific differences in nociception in rats. Pain. 2003; 104(1-2):367-73. DOI: 10.1016/s0304-3959(03)00044-7. View