Paper Title
Influence of Gender on Analgesic Modulation of Tramadol in WISTAR Rats

Abstract
To investigate the effect of tramadol on pain threshold between male and female Wistar rats using plantar test and acetic acid-induced writhing test. A total of 48 Wistar rats (body weight 100-150 g), 24 each male and female were randomly divided into eight groups (n=6/group) (Group I, II, V, VI- 0.9% NaCl; 1 ml/kg/day i.p. and Group III,IV, VII, VIII- Tramadol 10 mg/kg/day i.p.) . The paw withdrawal latency was significantly decreased (p<0.001) and number of writhing movements were significantly increased (p<0.001) in female control group compared to male control group. In tramadol treated female rats, paw withdrawal latency was significantly decreased (p=0.005) and number of writhing movements were significantly increased (p<0.001) in comparison with the tramadol treated male rats. The present study revealed that female Wistar rats have lower pain threshold than male Wistar rats and also the analgesic effect of tramadol was more pronounced in male Wistar rats compared to female Wistar rats. At present, the available evidence does not support sex-specific tailoring of treatments; however, this is a conceivable outcome in the near future. Additional research to elucidate the mechanisms driving sex differences in pain responses is needed in order to foster future interventions to reduce these disparities in pain. Keywords - Sex hormone, Opioids, Writhing, Plantar test