The unpleasant sensation of pain is experienced by all human beings at a given point in life. When pain gets severe and/or chronic it requires medical treatment. For over a thousand years, opioid agonists have been employed therapeutically to treat pain, with the first reports of such use involving the alkaloid morphine dated to the second century B.C.(Waldhoer, Bartlett et al. 2004) The term opioid refers to any substance with opium-like activity. Opium is extracted from the juice of the poppy plant Papaver somniferum. Opium contains in excess of 20 different alkaloids, and for centuries its crude form was used for pain management and for its psychological effects. In 1806 the German pharmacist Serturner isolated a pure substance from opium, which he called morphine after the Greek god of dreams, Morpheus. Thereafter other alkaloids such as codeine (1832) and papaverine (1848) were isolated.(Reisine and Pasternak 1996) These discoveries paved the way for the use of pure alkaloids as opposed to crude opium in the medical profession. It became apparent that these alkaloids had a high potential for abuse and addiction. However, it was not until 1973 that the first descriptions of the pharmacological properties of morphine, along with other agonists and antagonists, at the level of the receptor were reported.(Pert, Pasternak et al. 1973) Opioid receptors are of therapeutic relevance because they constitute the primary targets in the clinical treatment of both acute and chronic pain. They are members of the superfamily of seven helix transmembrane (TM) proteins known as G-protein coupled receptors (GPCRs); so-called because they are coupled in the cytoplasmic side to a group of Gi/Go hetero-trimeric proteins called G-proteins: G┙, G┚ and G┛.(Eguchi M 2004) Currently four types of opioid receptors have been identified:  (mu for morphine),  (kappa for ketocyclazocine),  (delta for deferens given that it was originally discovered in the vas deferens of mice)(Waldhoer, Bartlett et al. 2004) and orphan opioid receptor-like 1. They are in turn sub-divided into additional subtypes on the basis of their ligand binding and pharmacological profiles: 1-2, 1-3, and 1-2.(Pasternak 1993; Blakeney, Reid et al. 2007) The ,  and  main types are the most studied, each playing a different role in pain sedation: the -receptor generates the most profound analgesia, but is also associated with constipation, respiratory depression, euphoria, tolerance, dependence and addition;(Schmauss and Yaksh 1984; Cowan, Zhu et al. 1988) the -receptor is involved in pain relief from thermal sources,(Mansour, Khachaturian et al. 1988) but like the μ-receptor, it is also associated with respiratory depression and addiction;(Abdelhamid, Sultana et al.