How do opioid analgesics such as morphine achieve pain relief?

Opioid analgesics, including morphine, primarily achieve pain relief by binding to mu-opioid receptors in the central nervous system (CNS). These receptors are a type of G-protein-coupled receptor that, when activated by opioids, produce a range of physiological effects that modulate pain perception.

When morphine binds to these mu-opioid receptors, it leads to an inhibition of neurotransmitter release from nociceptive primary afferent neurons, and simultaneously enhances the hyperpolarization of postsynaptic neurons in pain pathways. This combination of actions results in a significant reduction of the perception of pain. The mu-opioid receptors are widely distributed in areas of the brain involved in pain processing, such as the thalamus and the limbic system, further contributing to the analgesic and euphoric effects of these drugs.

Other options do not accurately reflect the primary mechanism of action of opioids. Blocking NMDA receptors is more related to certain types of analgesics, but not to morphine's mechanism. Increasing endorphin synthesis does not directly relate to the way morphine exerts its effects; instead, morphine mimics the action of endorphins by directly stimulating the mu-opioid receptors.