Correlation of gender and leptin with analgesic effect of tramadol in high fat diet induced obese rats

Introduction: Gender and obesity related influences on the experience of pain have received considerable empirical attention in recent years. Differences in pain sensitivity among individuals may have implications for pain management which might account in part for the variability in analgesic requirements between individuals. Aim: To investigate the correlation of gender and serum leptin level with analgesic modulation of tramadol in high fat diet induced obese Wistar rats. Materials and Methods: A total of 48 Wistar rats (24 each male and female; body weight 100-150 gm) were housed as two rats/ cage. In addition to the normal pellet diet, these animals were orally fed with a mixture of Vanaspati daalda+Coconut oil (3:1)-10 mL/kg/day for 90 days. After 90 days, these rats attained body weight approximately ≥300 gm (obese). Thereafter, each 24 male and 24 female obese 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-Test: Tramadol 10 mg/kg/day i.p.) for each nociception model-plantar test (12 male rats and 12 female rats) and acetic acid induced writhing test (12 male rats and 12 female rats). The treatment duration was of five days. Results: Paw Withdrawal Latency (PWL) was significantly decreased (p<0.001) and both number of writhing movements and serum leptin concentrations were significantly increased (p<0.001) in obese female control group compared to obese male control group. Tramadol treated both obese male and female rats had significantly increased PWL (p<0.001) and decreased both number of writhing movements and serum leptin concentration (p<0.001) in comparison with both obese male and female control groups respectively. In tramadol treated obese female rats, PWL was significantly decreased (p=0.048) and both number of writhing movements and serum leptin concentration were significantly increased (p<0.001) in comparison with the tramadol treated obese male rats. PWL was negatively correlated with serum leptin concentration (Pearson correlation coefficient=-0.754, 2-tailed significance; p<0.001), and number of writhing movements were positively correlated with serum leptin concentration (Pearson correlation coefficient=0.507, 2-tailed significance; p=0.011). Conclusion: The present study revealed that obese female rats have more serum leptin concentration than obese male rats which could be one of the possible reasons for having more pain sensation to noxious stimuli in obese female rats compared to obese male rats. Tramadol treatment at the dose of 10 mg/ kg for five days has decreased serum leptin level in rats which might be one of the additional analgesic mechanisms of action of tramadol.