[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
:: Volume 18, Issue 1 (spring 2018) ::
J Ardabil Univ Med Sci 2018, 18(1): 70-79 Back to browse issues page
Effects of Testosterone on Analgesia in Formalin-Treated Mice
Akram Alijani , Rahmatoolah Parandin , Namdar Yousofvand , SHahrbanoo Oryan
Department of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran
Abstract:   (6341 Views)
Background & objectives: So far, various reports have been presented on the relationship between sex hormones and gender-related differences in pain and analgesia in humans and laboratory animals. The purpose of this study was to investigate the effect of testosterone hormone and spironolactone anti-androgen drug on morphine-induced analgesia in male mice using formalin test.
Methods: In this study, 80 male mice were divided into 10 groups (N=8); normal saline (control), sesame seed oil (as testosterone solvent), testosterone (5 and 10 mg/kg body weight), spironolactone, morphine, sesame seed oil + morphine, testosterone (5 and 10 mg/ kg body weight) + morphine and spironolactone + morphine. Formalin test was performed in all the mice, and data were analyzed by one-way ANOVA.
Results: The results showed that sesame seed oil + morphine (p<0.001), morphine (p<0.001), testosterone (5 mg/kg) + morphine (p<0.01) and testosterone (10 mg/kg) + morphine (p<0.001) significantly reduced acute  pain, and testosterone (5 mg/kg) (p<0.05), testosterone (10 mg/kg) (p<0.01), sesame seed oil + morphine (p<0.001), morphine (p<0.001), testosterone (5 mg/kg) + morphine (p<0.001) and testosterone (10 mg/kg) + morphine (p<0.001) significantly reduced chronic pain compared with control group. Spironolactone had no effect on pain relief in the presence and absence of morphine compared to control group.
Conclusions: It can be concluded that testosterone has analgesic effects on the chronic phase of the pain. On the other hand, spironolactone may have hyperalgesic effects due to its anti-androgenic properties.
Keywords: Testosterone, Analgesia, Morphine, Spironolactone
Full-Text [PDF 220 kb]   (1517 Downloads)    
Type of Study: article | Subject: General
Received: 2017/08/21 | Accepted: 2017/12/21 | Published: 2018/03/29
1. Schug SA, Goddard C. Recent advances in the pharmacological management of acute and chronic pain. Ann Palliat Med. 2014 Oct; 3(4): 263-75.
2. Rosenblum A, Marsch LA, Joseph H, Portenoy RK. Opioids and the Treatment of Chronic Pain: Controversies, Current Status, and Future Directions. Exp Clin Psychopharmacol. 2008 Oct; 16(5): 405–16. [DOI:10.1037/a0013628]
3. Lee CWS, Ho IK. Sex differences in opioid analgesia and addiction: interactions among opioid receptors and estrogen receptors. Mol Pain. 2013 Sep: 9: 45. [DOI:10.1186/1744-8069-9-45]
4. Graziani M, Nistico R. Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy. Front Pharmacol. 2015 Jun; 6: 122. [DOI:10.3389/fphar.2015.00122]
5. Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013 Jul; 111(1): 52-8. [DOI:10.1093/bja/aet127]
6. Dahan A, Kest B, Waxman AR, Sarton E. Sex-specific responses to opiates: animal and human studies. Anesth Analg. 2008 Jul; 107(1): 83-95. [DOI:10.1213/ane.0b013e31816a66a4]
7. Kandel ER, Schwartz JH, Jessell TM, Siegelbaum SA, Hudspeth AJ, Mack S Eds. Principles of Neural Science, 5th ed,New York, NY: McGraw-Hill; 2012. 1389-1400.
8. Hussain AM, Khan FA, Ahmed A, Chawla T, Azam SI. Effect of gender on pain perception and analgesic consumption in laparoscopic cholecystectomy: An observational study. J Anaesthesiol Clin Pharmacol. 2013 Ju-Sep; 29(3): 337-41.
9. Palmeira CC, Ashmawi HA, Posso Ide P. Sex and pain perception and analgesia. Rev Bras Anestesiol. 2011 Nov-Dec; 61(6): 814-28. [DOI:10.1016/S0034-7094(11)70091-5]
10. Fillingim RB1, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley JL. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain. 2009 May; 10(5): 447-85. [DOI:10.1016/j.jpain.2008.12.001]
11. Yousofvand N, Khani S, Nasri S. The Effects of Testosterone and Gonadectomy Conditions on Nociception and Their Effect on Morphine-Induced Analgesia in Male Mice, Using the formalin test. Armaghane- danesh. 2010; 15(3): 212-23. [Full text in Persian]
12. Karram T, Abbasi A, Keidar S, Golomb E, Hochberg I, Winaver J, et al. Effects of spironolactone and eprosartan on cardiac remodeling and angiotensin-converting enzyme isoforms in rats with experimental heart failure. Am J Physiol Heart Circ Physiol. 2005 Oct; 289(4): 1351-81. [DOI:10.1152/ajpheart.01186.2004]
13. Sembulingam K, Sembulingam P. Essential of Medical Physiology, 2nd ed. New Delhi: Yadav,2001: 7-254.
14. Hunskaar S, Hol K. The formalin test in mice: dissociation between inflammatory and non inflammatory pain. Pain J. 1997; 30: 103-14. [DOI:10.1016/0304-3959(87)90088-1]
15. Dubuisson D, Dennis SF. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain. 1997 Dec; 4(2): 161-74.
16. Daroogari SH, Parandin R, Yousofvand N, Shakibaie D. The Antinociceptive Effects of Topical Clove Oil Using Formalin Test in Male Mice. J Ardabil Univ Med Sci. 2017 sum; 17(2): 252-60. [Full text in Persian]
17. Aloisi AM,Ceccarelli I, Fiorenzani P, Massafra C. Testosterone affects formalin-induced responses differently in male and female rats. Neurosci Lett. 2004 May; 361(1-3); 262-4. [DOI:10.1016/j.neulet.2003.12.023]
18. Ceccarelli I, Fiorenzani P, Massafra C, Aloisi AM. Repeated nociceptive stimulation induces different behavioral and neuronal responses in intact and gonadectomized female rats. Brain Res. 2006 Aug; 1106(1): 142-9. [DOI:10.1016/j.brainres.2006.05.089]
19. Cook CD, Barrett AC, Roach EL, Bowman JR, Picker MJ. Sex-related differences in the antinociceptive effects of opioids: importance of rat genotype nociceptive stimulus intensity and efficacy at the opioid receptor. Psychopharmacology. 2000 Jul; 150: 430-42. [DOI:10.1007/s002130000453]
20. Stoffel EC, Ulibarri CM, Folk JE, Rice KC, Craft RM. Gonadal hormone modulation of Mu, Kappa, and Delta opioid antinociception in male and female rats. J Pain. 2005 Apr; 6(4): 261-74. [DOI:10.1016/j.jpain.2004.12.006]
21. Riley JL, Robinson ME, Wise EA, Price DD. A meta-analytic review of pain perception across the menstrual cycle. Pain. 1999 Jun; 81(3); 225-35. [DOI:10.1016/S0304-3959(98)00258-9]
22. Javan M, Ahmadiani A, Motamadi F, Kazemi B. Changes in G proteins genes expression in rat lumbar spinal cord support the inhibitory effect of chronic pain on the development of tolerance to morphine analgesia. Neurosci Res. 2005 Aug; 53(3): 250-56. [DOI:10.1016/j.neures.2005.06.020]
23. Boyer JS, Morgon MM, craft RM. Microinjection of morphine into the rostral ventromedial medulla produced greater antinociception in male compared to female rats. Brain Res. 1998 Jun; 796(1-2): 315-18. [DOI:10.1016/S0006-8993(98)00353-9]
24. Ali BH, Sharif Sh, Elkad A. Sex differences and the effect of gonadectomy on morphine-induced antinociception and dependence in rats and mice. Clin Exp Pharmacol Physiol. 1995 May; 22(5): 342-44. [DOI:10.1111/j.1440-1681.1995.tb02012.x]
25. Candido J, Lutfy K, Billings B, Sierra V, Duttaroy A, Inturrisi CE. Effect of adrenal and sex hormones on opioid analgesia and opioid receptor regulation. Pharmacol Biochem Behav. 1992 Aug; 42(4): 685-92. [DOI:10.1016/0091-3057(92)90015-8]
26. Loyd DR, Murphy AZ. The neuroanatomy of sexual dimorphism in opioid analgesia. Exp Neurol. 2014 Sep; 259: 57-63. [DOI:10.1016/j.expneurol.2014.04.004]
27. Serafini PC, Catalino J, Lobo RA. The effect of spironolactone on genital skin 5 alpha-reductase activity. J Steroid Biochem. 1985 Aug; 23(2): 191-4. [DOI:10.1016/0022-4731(85)90236-5]
28. Hammer RP Jr, Zhou L, Cheung S. Gonadal steroid hormones and hypothalamic opioid circuitry. Horm Behav. 1994 Dec; 28(4): 431-37. [DOI:10.1006/hbeh.1994.1040]
29. Keogh E, Herdenfeldt M. Gender, coping and the perception of pain. Pain. 2002 Jun; 97(3); 195-201. [DOI:10.1016/S0304-3959(01)00427-4]
30. Nestler EJ. Historical review: Molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharmacol Sci. 2004 Apr; 25(4): 210-8. [DOI:10.1016/j.tips.2004.02.005]
31. Vander Horst VG, Meij E, Schasfoort FC, Leeuwen FWV, Holstege G. Estrogen receptor- immunoreactive neurons in the lumbosacral Cord projection to the periaqueductal gray in the ovariectomized female cat. Neurosci Lett. 1997 Oct; 236(1): 25-8. [DOI:10.1016/S0304-3940(97)00750-7]
32. Meunier JC. Opioid Receptors, Tolerance and Dependence. Therapie. 1992 Nov; 47(6): 495-502.
33. McEwen BS. Invited review: Estrogens effects on the brain: multiple sites and molecular mechanisms. Journal of applied physiology. 2001 Dec 1;91(6):2785-801. [DOI:10.1152/jappl.2001.91.6.2785]
34. Carr BR. The effect of spironolactone on aromatase activity. Fertil Steril. 1986 May;45(5): 655-8. [DOI:10.1016/S0015-0282(16)49337-4]
35. Decker C, Sugiyama K, Underwood M, Correia MA. Inactivation of rat hepatic cytochrome P-450 by spironolactone. Biochem Biophys Res Commun. 1986 May; 136(3): 1162-9. [DOI:10.1016/0006-291X(86)90456-0]
36. Abdel-Salam OME, Baiuomy AR, Nada SA. Effects of spironolactone on pain responses in mice. EXCLI J. 2010 Feb; 9: 46-57.
37. Geerling JC, Kawata M, Loewy AD. Aldosterone- sensitive neurons in the rat central nervous system. J Comp Neurol. 2006 Jan; 494(3): 515-27. [DOI:10.1002/cne.20808]
38. Sonder SU, Mikkelsen M, Rieneck K, Hedegaard CJ, Bendtzen K. Effects of spironolactone on human blood mononuclear cells: mineralocorticoid receptor independent effects on gene expression and late apoptosis induction. Br J Pharmacol. 2006 May; 148(1): 46-53. [DOI:10.1038/sj.bjp.0706700]
39. Hansen PR, Rieneck K, Bendtzen K. Spironolactone inhibits production of proinflammatory cytokines by human mononuclear cells. Immunol Lett. 2004 Feb;91(2-3):87-91. [DOI:10.1016/j.imlet.2003.11.008]
Send email to the article author

Add your comments about this article
Your username or Email:


XML   Persian Abstract   Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Alijani A, Parandin R, Yousofvand N, Oryan S. Effects of Testosterone on Analgesia in Formalin-Treated Mice . J Ardabil Univ Med Sci 2018; 18 (1) :70-79
URL: http://jarums.arums.ac.ir/article-1-1528-en.html

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 18, Issue 1 (spring 2018) Back to browse issues page
مجله دانشگاه علوم پزشکی اردبیل Journal of Ardabil University of Medical Sciences
Persian site map - English site map - Created in 0.06 seconds with 30 queries by YEKTAWEB 4502