Physiology of Spinal Opioids and its relevance for Pain Management Selection

Widespread medical use of unprocessed opium was a common practice along the centuries until morphine was fi rst discovered in 1804 by Friedrich Sertürner, a German Pharmacist, who fi rst distributed this drug in 1817 [1]. The Romanian surgeon Racoviceanu-Pitesti, who reported his experience using a mixture of cocaine and morphine in 1901, made the fi rst publication concerning the use of opioids in spinal anesthesia [2]. After the development of new opioid in the 1940s, scientists began to believe that there must exist original binding sites within the brain for these opiate-like drugs. The problems were overcome in 1973 when Pert and Snyder further characterized the properties of this opiate binding from nervous tissue [3]. Not only did these binding sites reside within the brain, but they also lay in the gelatinous substance of the spinal cord. Fields et al., found that primary afferent tissue of the dorsal root and the dorsal horn of the spinal cord contained multiple receptor types [4]. The year 1975 was a crucial one regarding the discovery of endogenous enkephalins by Kosterlitz et al. [5]. Further, it was proven by Yaksh et al., that direct application of morphine into the spine of rats by a chronic intrathecal (IT) catheter produced analgesia [6] and this practice became a reality when Wang et al., successfully used intrathecal morphine bolus dose injection in humans [7]. The publication by Behar et al., in 1979 was the fi rst paper on the use of epidural morphine at 2 mg doses for the treatment of acute and chronic pain [8]. The latter authors suggested that there was a direct spinal opioid effect on the specifi c receptors of the spinal cord. Therefore, more than a hundred years passed until it became routine to use neuraxial opioids for acute pain analgesia.