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 ...

       Caffeine, an adenosine A1, A2A, and A2B receptor antagonist, is frequently used as an adjuvant analgesic in combination with non steroidal anti-inflammatory drugs or opioids. The aim of this study was to evaluate the effects of caffeine on preventing the development of morphine tolerance and analgesia in mice. In this study, different groups of mice recei...

Tolerance to opioid administration represents a serious medical alert in different chronic conditions. This study compares the effects of the imidazoline compounds 1, 2, and 3 on morphine tolerance in an animal model of inflammatory pain in the rat. 1, 2, and 3 have been selected in that, although bearing a common scaffold, preferentially bind to α2-adrenoceptors, imidazoline I2 receptors, or b...

Background Metabotropic glutamate receptor 5 has been suggested by many rodent studies to be a promising target for the development of novel analgesic drugs. The lack of approved compounds has prevented proof-of-concept studies in human subjects. Here we describe preclinical and translational studies of the mGlu5 negative allosteric mod-ulator (NAM), fenobam. Fenobam was tested for analgesic ef...

The effect of oxymatrine on the development of tolerance to the antinociceptive effects of morphine was investigated in rats. The degree of tolerance was assessed using the tail-flick test before and after 6 days of twice daily administration of oxymatrine premorphine (10/20/30 mg/kg). High doses of oxymatrine inhibited the development of morphine tolerance (resembling the effect of 7.5 mg/kg o...

The neuropeptide orphanin FQ/nociceptin (OFQ/N) has been shown to counteract several effects of endogenous and exogenous opioids, and it has been proposed as an opioid-modulating agent involved in the development of morphine tolerance and dependence. However, conflicting results have been obtained from animal models using different protocols to induce morphine tolerance. Here, we report that bo...