Possible mechanisms of morphine analgesia

The body has an endogenous analgesic system that prevents excess pain from interfering with the normal body functions. Depression of pain sensations occurs within the dorsal horn of the spinal cord where the primary pain fibers, which transmit pain sensations from the periphery, synapse with neurons that transmit pain to the higher centers. There appear to be two mechanisms by which the transmission of pain sensations are depressed; these include hyperpolarization of interneurons within the dorsal cord and depressing the release of the neurotransmitters associated with pain transmission. Activation of the analgesic mechanisms results from an interaction between specific neurotransmitters, such as enkephalin, serotonin, or norepinephrine, and specific receptors located on the neurons that transmit pain. The spinal analgesic mechanisms can be activated by either pain or nonpainful sensations arriving from the periphery or by supraspinal mechanisms. The supraspinal mechanisms originate in specific structures within the brainstem that include the periaqueductal gray matter, locus ceruleus, and nuclei in the medulla. These systems are activated either by ascending pain impulses or by higher centers such as the cortex or hypothalamus that, in turn, activate the spinal analgesic systems. There are three systems associated with activation of the supraspinal mechanisms. These include the opioid system associated with the release of the endorphins, the adrenergic system associated with the release of norepinephrine, and the serotonergic system associated with the release of serotonin. The interaction between these systems activates the spinal analgesic system. When the endogenous analgesic systems fail to control pain, analgesic drugs can be used to enhance the endogenous systems. Opiate drugs, such as morphine, interact with opioid receptors and produce analgesia by the same mechanisms as enkephalin, i.e., hyperpolarization of interneurons and depressing the release of transmitters associated with transmission of pain. In addition, morphine can interact with opioid receptors located in the supraspinal structures and activate the supraspinal system. Adrenergic drugs that interact with specific receptors also produce analgesia and it has been suggested that morphine interacts with the adrenergic system to produce analgesia.