Analgesic effect

During the Civil War of 1860s in the U.S., veterans were treated with opioids, especially morphine, for their pain relief. And after that, World War II enhanced this effect by opening “nerve block clinics”. Since the abuse problem arose, the doctors became aware of the issue and tried to avoid prescribing opioids. Around 1980, public opinion towards opioids was relatively relaxed due to several studies pointing out the fact that opioids are not that addictive, particularly with the birth of OxyContin in 1996. The class opioids can be divided into two categories: prescription medications such as morphine, and illegal ones which include heroin.

The major and the most direct effect of opioids is analgesia by binding to opioid receptors in the central and peripheral nervous system to treat acute and chronic noncancer pain. Another localization of opioid receptors is in the gastrointestinal tract. A typical acute pain situation is when there is intraoperative, postoperative, or posttraumatic pain. Comparing its common use on acute pain, the one on chronic noncancer is more controversial because of the unclear underlying mechanism and a lack of general psychosocial features in a long-term study.

Mechanism of action of µ-opioid receptor agonists in the spinal cord

Among three types of opioid receptors, µ, κ, and δ, most exogenous agonists bind to µ receptors in order to initiate potent analgesic effects.

All opioid receptors are linked through G proteins. In the dorsal horn of the spinal cord, activation of the µ receptor in the presynaptic terminal decreases the transmitter releasing through inhibition of Ca2+ influx facing an action potential. In the meantime, the postsynaptic µ receptor increases K+ conductance by facilitating the opening of potassium channels and, thereby, causing the hyperpolarization and decrease of the postsynaptic response to excitatory neurotransmission, thus, we feel less pain.

By mimicking the natural endogenous peptides (enkephalins, endorphins, and dynorphins), morphine, as the most widely used analgesic, doesn’t change the sensor threshold but keeps the patients out of pain that troubles them. Morphine reduced strongly and predominantly the pain through the descending pathways from the brainstem to the dorsal horn. Besides morphine, codeine, fentanyl, and methadone are frequently used in patients with pain.