Mechanism of Action of Narcotic Analgesics
The mechanism of narcotic analgesics is based on the concept of substitution. The human body has its own antinociceptive (pain-relief) system that utilizes endogenous opioids, specifically enkephalins.
Upon exogenous administration of pharmacological agents (such as morphine), these internal substances are artificially mimicked. Morphine directly binds to opioid receptors across various structures of the central nervous system, triggering a cascade of reactions divided into supraspinal (in the brain) and spinal (in the spinal cord) effects.
Effects on the Cortex and Thalamus: Altered Perception
The first major aspect of supraspinal action is realized at the level of higher integrative centers — the thalamus and the cerebral cortex.
When morphine binds to opioid receptors in these regions, a unique pharmacological phenomenon occurs:
- The emotional perception of the pain stimulus is altered.
- Negative psychoemotional components are completely eliminated: fear, anxiety, and profound suffering disappear.
- Paradoxically, the raw physical sensation of pain may partially persist, but it no longer troubles the individual and loses its destructive power.
Effects on the Midbrain: Activating Descending Control
The second critical level of supraspinal action is the midbrain. Here, the key target for morphine is the periaqueductal gray (PAG).
- The drug activates neurons within the periaqueductal gray.
- This activation acts as a trigger, initiating heightened neural firing.
- Generated signals travel downward along specialized descending inhibitory pathways.
This process establishes descending control, which is essential for suppressing pain signals at lower levels of the nervous system.
Integration of Supraspinal and Spinal Mechanisms
Supraspinal influence is inextricably linked to spinal action. Descending pathways activated by morphine in the brain project to the spinal cord, utilizing specialized neurotransmitters — norepinephrine (NE) and serotonin (5-HT).
As a result, enkephalin release is massively stimulated at the spinal cord level. Simultaneously, morphine exerts a direct inhibitory effect by binding to opioid receptors on presynaptic and postsynaptic membranes of neurons in the posterior horns (dorsal horns). Consequently, pain transmission undergoes a powerful dual block.
Summary Pharmacological Effect
The summation of all described mechanisms leads to the primary result — the disruption of pain impulse transmission from the spinal cord to the cerebral cortex. The ascending pain pathway is interrupted (blocked), which clinically manifests as profound analgesia — the complete elimination of pain sensitivity while maintaining consciousness.