GABA Agonists could Decrease Hyperalgesia and NO Serum Level in Morphine Tolerance Model

Several studies have demonstrated that nitric oxide (NO) is involved in hyperalgesia induced by NMDA activity in Morphine tolerance and NO synthase inhibitors can attenuate hyperalgesia in morphine tolerance. In addition, one of the possible mechanisms in morphine tolerance is reduction of GABA inhibitory effect. For this reason, we used GABA agonists (muscimol and baclofen) to investigate the effect of GABA agonists on analgesic effect of morphine and NO level of serum. In this study, experimental rats were divided into 4 groups as follows: 1. Control group, 2. Morphine tolerance group, 3. Morphine tolerance + muscimol, and 4-morphine tolerance + baclofen. To induce morphine tolerance in rats, the animals received 10 mg/kg of morphine sulfate intraperitoneal (ip) once a day for 8 days. In the treatment group, GABA agonist was injected on the 1^st, 3^rd, 5^th, and 8^th day before morphine injection. Finally, to evaluate GABA agonists treatment on morphine analgesia and hyperalgesia on the 8^th day of the study, thermal hyperalgesia was used to evaluate tolerance and hyperalgesia. Then, NO level of serum was investigated as an important factor in OIH. The results indicated that GABA agonists reduced thermal hyperalgesia in the morphine tolerance group (p 0.05). Furthermore, in the morphine tolerance group, NO significantly increased in comparison to the control group (p 0.01); however, after treatment with GABA agonists, NO decreased in the morphine tolerance group (P 0.01). This study indicates that GABA agonists even under effective dose decreased the NO released by activation of NMDA and improved OIH