CORRELATION OF GENDER AND LEPTIN WITH ANALGESIC EFFECT OF TRAMADOL IN RATS

Authors

  • Shakta Mani Satyam Department of Pharmacology, Melaka Manipal Medical College, Manipal Campus, Manipal Academy of Higher Education,Manipal – 576 104, Karnataka, India.
  • Laxminarayana Kurady Bairy Department of Pharmacology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, UAE
  • Vasudha Devi Department of Pharmacology, Melaka Manipal Medical College, Manipal Campus, Manipal Academy of Higher Education,Manipal – 576 104, Karnataka, India

DOI:

https://doi.org/10.22159/ajpcr.2018.v11i6.26678

Keywords:

Pain threshold, Sex hormone, Leptin, Opioids, Obesity, Writhing, Plantar, Acetic acid

Abstract

 Objective: The objective of the study was to investigate the correlation of gender and serum leptin level with analgesic modulation of tramadol in Wistar rats.

Methods: A total of 48 Wistar rats (body weight 100–150 g), 24 each male and female Wistar rats were randomly divided into two groups (n=6/group) (Group I - Control- 0.9% NaCl; 1 ml/kg/day i.p. and Group II - Tramadol 10 mg/kg/day i.p.) for each nociception model - plantar test and acetic acid induced writhing test. The treatment duration was of 5 days. Paw withdrawal latency (PWL) was assessed using plantar test and writhing movements were observed following administration of 0.8% acetic acid; 10 ml/kg i.p.

Results: PWL was significantly decreased (p<0.001) and both number of writhing movements and serum leptin concentrations were significantly increased (p<0.001) in female control group compared to male control group. In tramadol treated female rats, PWL was significantly decreased (p=0.005) and both number of writhing movements and serum leptin concentrations were significantly increased (p<0.001) in comparison with the tramadol treated male rats. PWL was negatively correlated with serum leptin concentration (Pearson correlation coefficient= −0.826, two-tailed significance= 0.000), and writhing movements were positively correlated with serum leptin concentration (Pearson correlation coefficient= 0.505, two-tailed significance= 0.012).

Conclusions: The present study revealed that female rats have more serum leptin concentration than male rats which could be one of the possible reasons for having more pain sensitivity to noxious stimuli in female rats compared to male rats. Tramadol treatment at the dose of 10 mg/kg for 5 days has decreased serum leptin level in rats which might be one of the additional mechanisms of tramadol to reduce pain.

Downloads

Download data is not yet available.

Author Biographies

Shakta Mani Satyam, Department of Pharmacology, Melaka Manipal Medical College, Manipal Campus, Manipal Academy of Higher Education,Manipal – 576 104, Karnataka, India.

Lecturer in Pharmacology, Melaka Manipal Medical College, Manipal Campus, Manipal Academy of Higher Education, Manipal-576104, Karnataka (INDIA).

Laxminarayana Kurady Bairy, Department of Pharmacology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, UAE

Associate Dean- Basic Sciences, Professor & Chairperson- Pharmacology, RAK College of Medical Sciences, RAK Medical & Health Sciences University, UAE.

 

Vasudha Devi, Department of Pharmacology, Melaka Manipal Medical College, Manipal Campus, Manipal Academy of Higher Education,Manipal – 576 104, Karnataka, India

Professor and Head of Pharmacology, Melaka Manipal Medical College, Manipal Campus, Manipal Academy of Higher Education, Manipal-576104, Karnataka (INDIA).

References

Scholz J, Woolf CJ. The neuropathic pain triad: Neurons, immune cells and glia. Nat Neurosci 2007;10:1361-8.

Fillingim RB. Sex differences in analgesic responses: Evidence from experimental models. Eur J Anaesthesiol 2002;19 Suppl. 26:16-24.

Isacson D, Bingefors K. Epidemiology of analgesic use: A gender perspective. Eur J Anaesthesiol 2002;19 Suppl. 26:5-15.

Starowicza K, Cocka BP. The role of melanocortins and their receptors in inflammatory processes, nerve regeneration and nociception. J Life Sci 2003;73:823-47.

Priyanka V, Rekha V. Analgesic, anti-inflammatory and antipyretic activity of Cissus quadrangularis. J Pharm Sci Technol 2010;2:111-8.

Maria TC, Cenzo C, Valentina O, Micaela M, Omar C. Synthesis of ibuprofen heterocyclic amides and investigation of their analgesic and toxicological properties. Euro J Med Chem 2003;38:513-8.

Biçer F, Eti Z, Aricioglu F, Konya D, Gogus Y. The effects of gabapentin, tramadol and amitriptyline on pain behavior in a rat neuropathic pain model: 14AP10-2. Euro J Anaesthesiol 2010;27:217.

Kepler KL, Standifer KM, Paul D, Kest B, Pasternak GW, Bodnar RJ. Gender effects and central opioid analgesia. Pain 1991;45:87-94.

Cicero TJ, Nock B, Meyer ER. Sex-related differences in morphine’s antinociceptive activity: Relationship to serum and brain morphine concentrations. J Pharmacol Exp Ther 1997;282:939-44.

Fillingim RB, Ness TJ, Glover TL, Campbell CM, Hastie BA, Price DD, et al. Morphine responses and experimental pain: Sex differences in side effects and cardiovascular responses but not analgesia. J Pain 2005;6:116-24.

Cicero TJ, Nock B, Meyer ER. Gender-related differences in the anti-nociceptive properties of morphine. J Pharmacol Exp Ther 1996;279:767-73.

Kest B, Palmese C, Hopkins E. A comparison of morphine analgesic tolerance in male and female mice. Brain Res 2000;879:17-22.

Finkelstein EA, Fiebelkorn IC, Wang G. State-level estimates of annual medical expenditures attributable to obesity. Obesity Res 2004;12:18-24.

World Health Organization. Obesity: Preventing and Managing the Global Epidemic. Geneva (Switzerland): World Health Organization; 1997.

Sirisha G, Rahul PB, Usha NS, Madhu DK. Evaluation of antidepressant effect of chronic administration of tramadol alone and in combination with fluoxetine in low doses in albino mice. Int J Pharm Pharm Sci 2014;6:101-5.

Chogtu B, Bairy KL, Satyam SM, Pirasanthan R, Gupta S. Analgesic modulation of tramadol, amitriptyline and gabapentin in male and female wistar rats. Res J Pharm Biol Chem Sci 2013;4:70-8.

Motaghinejad M, Ebrahimzadeh A, Shabab B. Preventive effect of central administration of venlafaxine on morphine physical dependence, nociception, and blood cortisol level in rat. Int J Prev Med 2014;5:1422-31.

Prabhu VV, Nalini G, Chidambaranathann N, Kisan SS. Evaluation of anti-inflammatory and analgesic activity of Tridax procumbens linn against formalin, acetic acid and CFA induced pain models. Int J Pharm Pharm Sci 2011;3:126-30.

Selim K, Sinan C, Suleyman S, Mete O, Mustafa S, Haluk K. Effects of central and peripheral administration of leptin on pain threshold in rats and mice. Neuroendocrinol Lett 2003;24:193-6.

Mendonca HC, Montenegro RM, Foss MC, Silva de Sa MF, Ferriani RA. Positive correlation of serum leptin with estradiol levels in patients with polycystic ovary syndrome. Braz J Med Biol Res 2004;37:729-36.

Shimizu H, Shimomura Y, Nakanishi Y, Futawatari T, Ohtani K, Sato N, Mori M. Estrogen increases in vivo leptin production in rats and human subjects. J Endocrinol 1997;154:285-92.

Messinis IE, Milingos S, Zikopoulos K, Kollios G, Seferiadis K, Lolis D. Leptin concentrations in the follicular phase of spontaneous cycles and cycles superovulated with follicle stimulating hormone. Hum Reprod 1998;13:1152-6.

Rosenbaum M, Nicolson M, Hirsch J, Heymsfield SB, Gallagher DY, Chu FL, et al. Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab 1996;81:3424-7.

Hickey MS, Israel RG, Gardiner SN, Considine RV, McCammon MR, Tyndall GL, et al. Gender differences in serum leptin levels in humans. Biochem Mol Med 1996;59:1-6.

Kennedy A, Gettys TW, Watson P, Wallace P, Ganaway E, Pan QI,

et al. The metabolic significance of leptin in humans: Gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure. J Clin Endocrinol Metab 1997;82:1293-300.

Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB, Flier JS. Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action. Nat Med 1995;1:1311-4.

Saad MF, Damani S, Gingerich RL, Riad-Gabriel MG, Khan A., Boyadjian R, et al. Sexual dimorphism in plasma leptin concentration. J Clin Endocrinol Metab 1997;82:579-84.

Bhasin S, Storer TW, Berman N, Yarasheski KE, Clevenger B, Phillips J, et al. Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab 1997;82:407-13.

Behre HM, Simoni M, Nieschlag E. Strong association between serum levels of leptin and testosterone in men. Clin Endocrinol (Oxf) 1997;47:237-40.

Ibrahim IY, Ibrahim HM, Aziz NM, Rahman DM. Effect of opioid receptors modulation on the HFD-Induced obesity in adult male Albino rats. Malays J Med Res 2014;25:72-81.

Anghel A, Jamieson C, Ren X, Young J, Porche R, Ozigbo E, et al. Gene expression profiling following short-term and long-term morphine exposure in mice uncovers genes involved in food intake. Neurosci 2010;167:554-66.

Alvarez P, Bogen O, Chen X, Giudice LC, Levine JD. Ectopic endometrium-derived leptin produces estrogen dependent chronic pain in a rat model of endometriosis. Neuroscience 2014;258:111-20.

Kutlu S, Canpolat S, Sandal S, Ozcan M, Sarsilmaz M, Kelestimur H. Effects of central and peripheral administration of leptin on pain threshold in rats and mice. Neuro Endocrinol Lett 2003;24:193-6.

Hosoi T, Okuma Y, Nomura Y. Leptin regulates interleukin-1beta expression in the brain via the STAT3-independent mechanisms. Brain Res Mol Brain Res 2002;13:139-46.

Lim G, Wang S, Zhang Y, Tian Y, Mao J. Spinal leptin contributes to the pathogenesis of neuropathic pain in rodents. J Clin Invest 2009;119:295-304.

Maeda T, Kiguchi N, Kobayashi Y, Ikuta T, Ozaki M, Kishioka S. Leptin derived from adipocytes in injured peripheral nerves facilitates development of neuropathic pain via macrophage stimulation. Proc Natl Acad Sci USA 2009;106:13076-81.

Published

07-06-2018

How to Cite

Satyam, S. M., L. K. Bairy, and V. Devi. “CORRELATION OF GENDER AND LEPTIN WITH ANALGESIC EFFECT OF TRAMADOL IN RATS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 11, no. 6, June 2018, pp. 493-7, doi:10.22159/ajpcr.2018.v11i6.26678.

Issue

Section

Original Article(s)