Assessing Pain Behavioral Responses and Neurotrophic Factors in the Dorsal Root Ganglion, Serum and Peritoneal Fluid in Rat Models of Endometriosis
,
Abstract
Objective: Pain is the most frequently reported symptom involving in endometriosis. The alterations of neurotrophic factors and certain neuropeptides in the dorsal root ganglion (DRG), as well as serum and peritoneal fluid (PF), were evaluated in rat models of endometriosis.
Materials and methods: Twenty-four Sprague Dawley female rats were selected and maintained in a standard condition with 12 hours’ dark-light cycles. All the rats were randomly assigned to 3 groups: Control (intact rats); Sham (the operation was conducted without endometriosis induction); and Endometriosis (endometriosis induction was performed). The formalin test was performed for all groups on the first and the 21st day of the study. The assessments of Brain-Derived Neurotrophic Factor (BDNF), Nerve Growth Factor (NGF), Calcitonin Gene-Related Peptide (CGRP), and Substance P levels were carried out by enzyme-linked immunosorbent assay (Elisa). The data were analyzed by One-Way ANOVA. The Tukey’s test was used as post-hoc.
Results: Endometriosis induction significantly increased the mean pain scores in the endometriosis group in all three phases of the formalin test. The concentrations of DRG-CGRP (p=0.035), BDNF (p<0.001), and NGF (p=0.006) in the endometriosis group were significantly higher than that of the other groups while serum-BDNF (p<0.001), Substance P (p=0.009), and NGF (p=0.015) were significantly lower in endometriosis group compared to other groups. The concentrations of PF-BDNF (p=0.025) and Substance P (p=0.009) were significantly lower than those of other groups.
Conclusion: The present results delineate that endometriosis induction could lead to hyperalgesia. This may be related to the significant increases in the BDNF, NGF, and CGRP in DRG.
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4. Zhang Q, Dong P, Liu X, Sakuragi N, Guo S-W. Enhancer of Zeste homolog 2 induces epithelial-mesenchymal transition in endometriosis. Sci Rep 2017; 7: 6804.
5. Coxon L, Horne AW, Vincent K. Pathophysiology of endometriosis-associated pain: A review of pelvic and central nervous system mechanisms. Best Pract Res Clin Obstet Gynaecol 2018; 51: 53-67.
6. Lian YL, Cheng MJ, Zhang XX, Wang L. Elevated expression of transient receptor potential vanilloid type 1 in dorsal root ganglia of rats with endometriosis. Mol Med Rep 2017; 16: 1920-6.
7. Miller EJ, Fraser IS. The importance of pelvic nerve fibers in endometriosis. Womens Health . 2015; 11: 611-8.
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9. Tokushige N, Markham R, Russell P, Fraser IS. Nerve fibres in peritoneal endometriosis. Hum Reprod 2006; 21: 3001-7.
10. Berkley KJ, Rapkin AK, Papka RE. The pains of endometriosis. Science 2005; 308: 1587-9.
11. Schou WS, Ashina S, Amin FM, Goadsby PJ, Ashina M. Calcitonin gene-related peptide and pain: a systematic review. J Headache Pain 2017; 18: 34.
12. Zhang G, Dmitrieva N, Liu Y, McGinty KA, Berkley KJ. Endometriosis as a neurovascular condition: estrous variations in innervation, vascularization, and growth factor content of ectopic endometrial cysts in the rat. Am J Physiol Regul Integr Comp Physiol 2008; 294: R162-71.
13. Barcena de Arellano ML, Arnold J, Lang H, Vercellino GF, Chiantera V, Schneider A, Mechsner S. Evidence of neurotrophic events due to peritoneal endometriotic lesions. Cytokine 2013; 62: 253-61.
14. Kobayashi H, Yamada Y, Morioka S, Niiro E, Shigemitsu A, Ito F. Mechanism of pain generation for endometriosis-associated pelvic pain. Arch Gynecol Obstet 2014; 289: 13-21.
15. Stefani LC. BDNF and serum S100B levels according the spectrum of structuralpathology in chronic pain patients. Neurosci Lett 2019; 706: 105-9.
16. Ding S, Zhu T, Tian Y, Xu P, Chen Z, Huang X, et al. Role of Brain-Derived Neurotrophic Factor in Endometriosis Pain. Reprod Sci 2018; 25: 1045-57.
17. Rocha AL, Vieira EL, Ferreira MC, Maia LM, Teixeira AL, Reis FM. Plasma brain-derived neurotrophic factor in women with pelvic pain: a potential biomarker for endometriosis? Biomark Med 2017; 11: 313-17.
18. Wessels JM, Leyland NA, Agarwal SK, Foster WG. Estrogen induced changes in uterine brain-derived neurotrophic factor and its receptors. Hum Reprod 2015; 30: 925-36.
19. Perricos A, Ashjaei K, Husslein H, Proestling K, Kuessel L, Obwegeser R, et al. Increased serum levels of mBDNF in women with minimal and mild endometriosis have no predictive power for the disease. Exp Biol Med (Maywood) 2018; 243: 50-6.
20. Morotti M, Vincent K, Brawn J, Zondervan KT, Becker CM. Peripheral changes in endometriosis-associated pain. Hum Reprod Update 2014; 20: 717-36.
21. Barcena de Arellano ML, Arnold J, Vercellino GF, Chiantera V, Ebert AD, et al. Influence of nerve growth factor in endometriosis-associated symptoms. Reprod Sci 2011; 18: 1202-10.
22. Jin Z, Wang L, Zhu Z. Effect of GuiXiong Xiaoyi Wan
in Treatment of Endometriosis on Rats. Evid Based Complement Alternat Med 2015; 2015: 208514.
23. Rudzitis-Auth J, Nenicu A, Nickels RM, Menger MD, Laschke MW. Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions. Am J Pathol 2016; 186: 2129-42
24. Taherianfard M, Mosavi M. Hippocampal GABA(A) Receptor and Pain Sensitivity during Estrous Cycle in the Rat. Iran J Med Sci 2011; 36: 289-95.
25. Do Amaral VF, Dal Lago EA, Kondo W, Souza L, Francisco JC. Development of an experimental model of endometriosis in rats. Rev Col Bras Cir 2009; 36: 250-5.
26. Wen J, Sun D, Tan J, Young W. A Consistent, Quantifiable, and Graded Rat Lumbosacral Spinal Cord Injury Model. J Neurotrauma 2015; 32: 875-92.
27. Li J, Micevych P, McDonald J, Rapkin A, Chaban V. Inflammation in the uterus induces phosphorylated extracellular signal-regulated kinase and substance P immunoreactivity in dorsal root ganglia neurons innervating both uterus and colon in rats. J Neurosci Res. 2008; 86: 2746-52.
28. Goetz TG, Mamillapalli R, Taylor HS. Low Body Mass Index in Endometriosis Is Promoted by Hepatic Metabolic Gene Dysregulation in Mice. Biol Reprod 2016; 95: 115.
29. Moradi M, Parker M, Sneddon A, Lopez V, Ellwood D. Impact of endometriosis on women’s lives: a qualitative study. BMC Womens Health 2014; 14: 123.
30. Hernandez S, Cruz ML, Torres-Reveron A, Appleyard CB. Impact of physical activity on pain perception in an animal model of endometriosis. J Endometr Pelvic Pain Disord 2015; 7: 89-114.
31. Bruner-Tran KL, Mokshagundam S, Herington JL, Ding T, Osteen KG. Rodent Models of Experimental Endometriosis: Identifying Mechanisms of Disease and Therapeutic Targets. Curr Womens Health Rev 2018; 14: 173-88.
32. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Human Reproduction Update 2011; 17: 327-46.
33. McKinnon BD, Bertschi D, Bersinger NA, Mueller MD. Inflammation and nerve fiber interaction in endometriotic pain. Trends Endocrinol Metab 2015; 26: 1-10.
34. Huang Y. Expression of BDNF in dorsal root ganglion of rats with bone cancer pain and its effect on pain behavior. J Musculoskelet Neuronal Interact 2018; 18: 42-6.
35. Qin X , Liu Y , Feng Y , Jiang J . Ginsenoside Rf alleviates dysmenorrhea and inflammation through the BDNF-TrkB-CREB pathway in a rat model of endometriosis. Food Funct 2019; 10: 244-9.
36. Dewanto A, Dudas J, Glueckert R, Mechsner S, Schrott-Fischer A, Wildt L, et al. Localization of TrkB and p75 receptors in peritoneal and deep infiltrating endometriosis: an immunohistochemical study. Reprod Biol Endocrinol 2016; 14: 43.
37. Li Y, Zhang SF, Zou SE, Xia X, Bao L. Accumulation of nerve growth factor and its receptors in the uterus and dorsal root ganglia in a mouse model of adenomyosis. Reprod Biol Endocrinol 2011; 9: 30.
38. Fassbender A, Burney RO, O DF, D'Hooghe T, Giudice L. Update on Biomarkers for the Detection of Endometriosis. Biomed Res Int 2015; 2015: 130854.
39. Chiantera V, Abesadze E, Mechsner S. How to Understand the Complexity of Endometriosis-Related Pain. Journal of Endometriosis and Pelvic Pain
Disorders 2017: 1-8.
40. Medina MG, Lebovic DI. Endometriosis-associated nerve fibers and pain. Acta Obstet Gynecol Scand 2009; 88: 968-75.
41. Sanfilippo JS, Williams RS, Yussman MA, Cook CL, Bissonnette F. Substance P in peritoneal fluid. Am J Obstet Gynecol 1992; 166: 155-9.
2. Kyama MC, D'Hooghe TM, Debrock S, Machoki J, Chai DC, Mwenda JM. The prevalence of endometriosis among African-American and African-indigenous women. Gynecol Obstet Invest 2004; 57: 40-2.
3. Treloar S, Hadfield R, Montgomery G, Lambert A, Wicks J, Barlow DH, et al. The International Endogene Study: a collection of families for genetic research in endometriosis. Fertil Steril 2002; 78: 679-85.
4. Zhang Q, Dong P, Liu X, Sakuragi N, Guo S-W. Enhancer of Zeste homolog 2 induces epithelial-mesenchymal transition in endometriosis. Sci Rep 2017; 7: 6804.
5. Coxon L, Horne AW, Vincent K. Pathophysiology of endometriosis-associated pain: A review of pelvic and central nervous system mechanisms. Best Pract Res Clin Obstet Gynaecol 2018; 51: 53-67.
6. Lian YL, Cheng MJ, Zhang XX, Wang L. Elevated expression of transient receptor potential vanilloid type 1 in dorsal root ganglia of rats with endometriosis. Mol Med Rep 2017; 16: 1920-6.
7. Miller EJ, Fraser IS. The importance of pelvic nerve fibers in endometriosis. Womens Health . 2015; 11: 611-8.
8. Greaves E, Horne AW, Jerina H, Mikolajczak M, Hilferty L, Mitchell R, et al. EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis. Sci Rep 2017; 7: 44169.
9. Tokushige N, Markham R, Russell P, Fraser IS. Nerve fibres in peritoneal endometriosis. Hum Reprod 2006; 21: 3001-7.
10. Berkley KJ, Rapkin AK, Papka RE. The pains of endometriosis. Science 2005; 308: 1587-9.
11. Schou WS, Ashina S, Amin FM, Goadsby PJ, Ashina M. Calcitonin gene-related peptide and pain: a systematic review. J Headache Pain 2017; 18: 34.
12. Zhang G, Dmitrieva N, Liu Y, McGinty KA, Berkley KJ. Endometriosis as a neurovascular condition: estrous variations in innervation, vascularization, and growth factor content of ectopic endometrial cysts in the rat. Am J Physiol Regul Integr Comp Physiol 2008; 294: R162-71.
13. Barcena de Arellano ML, Arnold J, Lang H, Vercellino GF, Chiantera V, Schneider A, Mechsner S. Evidence of neurotrophic events due to peritoneal endometriotic lesions. Cytokine 2013; 62: 253-61.
14. Kobayashi H, Yamada Y, Morioka S, Niiro E, Shigemitsu A, Ito F. Mechanism of pain generation for endometriosis-associated pelvic pain. Arch Gynecol Obstet 2014; 289: 13-21.
15. Stefani LC. BDNF and serum S100B levels according the spectrum of structuralpathology in chronic pain patients. Neurosci Lett 2019; 706: 105-9.
16. Ding S, Zhu T, Tian Y, Xu P, Chen Z, Huang X, et al. Role of Brain-Derived Neurotrophic Factor in Endometriosis Pain. Reprod Sci 2018; 25: 1045-57.
17. Rocha AL, Vieira EL, Ferreira MC, Maia LM, Teixeira AL, Reis FM. Plasma brain-derived neurotrophic factor in women with pelvic pain: a potential biomarker for endometriosis? Biomark Med 2017; 11: 313-17.
18. Wessels JM, Leyland NA, Agarwal SK, Foster WG. Estrogen induced changes in uterine brain-derived neurotrophic factor and its receptors. Hum Reprod 2015; 30: 925-36.
19. Perricos A, Ashjaei K, Husslein H, Proestling K, Kuessel L, Obwegeser R, et al. Increased serum levels of mBDNF in women with minimal and mild endometriosis have no predictive power for the disease. Exp Biol Med (Maywood) 2018; 243: 50-6.
20. Morotti M, Vincent K, Brawn J, Zondervan KT, Becker CM. Peripheral changes in endometriosis-associated pain. Hum Reprod Update 2014; 20: 717-36.
21. Barcena de Arellano ML, Arnold J, Vercellino GF, Chiantera V, Ebert AD, et al. Influence of nerve growth factor in endometriosis-associated symptoms. Reprod Sci 2011; 18: 1202-10.
22. Jin Z, Wang L, Zhu Z. Effect of GuiXiong Xiaoyi Wan
in Treatment of Endometriosis on Rats. Evid Based Complement Alternat Med 2015; 2015: 208514.
23. Rudzitis-Auth J, Nenicu A, Nickels RM, Menger MD, Laschke MW. Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions. Am J Pathol 2016; 186: 2129-42
24. Taherianfard M, Mosavi M. Hippocampal GABA(A) Receptor and Pain Sensitivity during Estrous Cycle in the Rat. Iran J Med Sci 2011; 36: 289-95.
25. Do Amaral VF, Dal Lago EA, Kondo W, Souza L, Francisco JC. Development of an experimental model of endometriosis in rats. Rev Col Bras Cir 2009; 36: 250-5.
26. Wen J, Sun D, Tan J, Young W. A Consistent, Quantifiable, and Graded Rat Lumbosacral Spinal Cord Injury Model. J Neurotrauma 2015; 32: 875-92.
27. Li J, Micevych P, McDonald J, Rapkin A, Chaban V. Inflammation in the uterus induces phosphorylated extracellular signal-regulated kinase and substance P immunoreactivity in dorsal root ganglia neurons innervating both uterus and colon in rats. J Neurosci Res. 2008; 86: 2746-52.
28. Goetz TG, Mamillapalli R, Taylor HS. Low Body Mass Index in Endometriosis Is Promoted by Hepatic Metabolic Gene Dysregulation in Mice. Biol Reprod 2016; 95: 115.
29. Moradi M, Parker M, Sneddon A, Lopez V, Ellwood D. Impact of endometriosis on women’s lives: a qualitative study. BMC Womens Health 2014; 14: 123.
30. Hernandez S, Cruz ML, Torres-Reveron A, Appleyard CB. Impact of physical activity on pain perception in an animal model of endometriosis. J Endometr Pelvic Pain Disord 2015; 7: 89-114.
31. Bruner-Tran KL, Mokshagundam S, Herington JL, Ding T, Osteen KG. Rodent Models of Experimental Endometriosis: Identifying Mechanisms of Disease and Therapeutic Targets. Curr Womens Health Rev 2018; 14: 173-88.
32. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Human Reproduction Update 2011; 17: 327-46.
33. McKinnon BD, Bertschi D, Bersinger NA, Mueller MD. Inflammation and nerve fiber interaction in endometriotic pain. Trends Endocrinol Metab 2015; 26: 1-10.
34. Huang Y. Expression of BDNF in dorsal root ganglion of rats with bone cancer pain and its effect on pain behavior. J Musculoskelet Neuronal Interact 2018; 18: 42-6.
35. Qin X , Liu Y , Feng Y , Jiang J . Ginsenoside Rf alleviates dysmenorrhea and inflammation through the BDNF-TrkB-CREB pathway in a rat model of endometriosis. Food Funct 2019; 10: 244-9.
36. Dewanto A, Dudas J, Glueckert R, Mechsner S, Schrott-Fischer A, Wildt L, et al. Localization of TrkB and p75 receptors in peritoneal and deep infiltrating endometriosis: an immunohistochemical study. Reprod Biol Endocrinol 2016; 14: 43.
37. Li Y, Zhang SF, Zou SE, Xia X, Bao L. Accumulation of nerve growth factor and its receptors in the uterus and dorsal root ganglia in a mouse model of adenomyosis. Reprod Biol Endocrinol 2011; 9: 30.
38. Fassbender A, Burney RO, O DF, D'Hooghe T, Giudice L. Update on Biomarkers for the Detection of Endometriosis. Biomed Res Int 2015; 2015: 130854.
39. Chiantera V, Abesadze E, Mechsner S. How to Understand the Complexity of Endometriosis-Related Pain. Journal of Endometriosis and Pelvic Pain
Disorders 2017: 1-8.
40. Medina MG, Lebovic DI. Endometriosis-associated nerve fibers and pain. Acta Obstet Gynecol Scand 2009; 88: 968-75.
41. Sanfilippo JS, Williams RS, Yussman MA, Cook CL, Bissonnette F. Substance P in peritoneal fluid. Am J Obstet Gynecol 1992; 166: 155-9.
| Files | ||
| Issue | Vol 14, No 4 (December 2020) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/jfrh.v14i4.5210 | |
| Keywords | ||
| Endometriosis Brain-Derived Neurotrophic Factor Nerve Growth Factor Calcitonin Gene-Related Peptide Substance P Rat | ||
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How to Cite
1.
Farahani Z, Taherianfard M, Naderi MM, Ferrero H. Assessing Pain Behavioral Responses and Neurotrophic Factors in the Dorsal Root Ganglion, Serum and Peritoneal Fluid in Rat Models of Endometriosis. J Family Reprod Health. 2020;14(4):259-268.
