Introduction: Estrogen and progesterone are supposed to modify pain sensitivity. However, the actual role of each of these steroid hormones in this respect is not well known. Plasma concentrations of these hormones show variation during estrous cycle. The role of alpha2 receptors in tonic pain has been pointed out. The aim of the present study was to investigate the agonist and antagonist effect of alpha2 adrenergic receptors on tonic pain sensitivity during all stages of estrous cycle in female rats. Methods: Xylasine as alpha2 agonist and yohimbin as alpha2 antagonist were used via intraperitoneal route (IP). Adult rats weighing 180-200 grams were used. Animals were maintained on 12h reverse light/dark cycle for 7 days prior to the experiment. Water and food was available ad libitum. Formalin test was performed by subcutaneous injection of 50 l formalin (2.5%) solution into the hind paw. Formalin test was performed in all stages of estrous cycle for 60 minutes. Animals were divided into four groups 1- control group (intact animal), 2- Sham group (animals received 0.2 ml normal saline by IP route), 3- Agonist groups (animals received 0.2 ml xylasine 1, 3 mg/kg body weight by IP route) and 4- Antagonist group (animals received 0.2 ml yohimbine 1, 3 mg/kg body weight by IP route). Data were statistically analyzed using 2 way ANOVA test followed by Tukey's test as post-hoc test. P<0.05 was considered significant. Results: Results showed that xylasine significantly (p<0.05) decreases pain sensitivity in all stages of estrous cycle. Analgesic effect of xylasine was maximum in estrus stage of estrous cycle and minimum in metestrus stage of estrous cycle. Yohimbine significantly (p<0.05) increases pain sensitivity in all stages of estrous cycle. Hyperalgesic effect of yohimbine was maximum in metestrus stage of estrous cycle and minimum in estrus stage of estrous cycle. Conclusion: These results indicate that alpha2 adrenergic system and endogenous steroids have an important role in pain sensitivity.

Keywords: Xylasine, Yohimbine, Formalin Test, Estrous cycle, Rats

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