Mechanism of action of narcotic analgesics
Understanding the mechanism of action of narcotic analgesics is based on the concept of substitution. The human body possesses its own antinociceptive (pain-relief) system, which utilizes endogenous opioids, specifically enkephalins.
Upon exogenous administration of pharmacological agents (using morphine as an example), there is an artificial imitation of the action of these internal substances. Morphine directly binds to opioid receptors in various structures of the central nervous system, triggering a cascade of reactions that can be divided into supraspinal (in the brain) and spinal (in the spinal cord) effects.
Effect on the cortex and thalamus: alteration of perception
The first critical aspect of supraspinal action is realized at the level of higher integrative centers — the thalamus and the cerebral cortex.
When morphine acts on opioid receptors in these zones, a unique pharmacological phenomenon occurs:
- The emotional perception of the pain stimulus is altered.
- The negative psychoemotional components are completely eliminated in the patient: fear, anxiety, and profound suffering disappear.
- At the same time, paradoxically, the physical sensation of pain itself may partially persist, but it ceases to bother the person and loses its destructive power.
Effect on the midbrain: triggering of descending control
The second critically important level of supraspinal action is the midbrain. Here, the key target for morphine is the periaqueductal gray matter.
- The drug activates the neurons of the periaqueductal gray matter.
- This activation serves as a trigger that initiates enhanced impulse generation.
- The generated signals are directed downward via specialized descending inhibitory pathways (in functional diagrams, they are often indicated by solid lines emphasizing their active status, unlike dashed lines of inactive pathways).
This process establishes descending control, which is essential for suppressing pain signals at lower levels of the nervous system.
Connection of supraspinal and spinal mechanisms
Supraspinal influence is inextricably linked with spinal action. The descending pathways activated by morphine in the brain descend to the spinal cord and utilize specific neurotransmitters — norepinephrine (NE) and serotonin (5-HT).
As a result, there is a massive stimulation of enkephalin release already at the spinal cord level. Concurrently, morphine exerts a direct inhibitory effect by binding to opioid receptors on the pre- and postsynaptic membranes of dorsal horn neurons. Consequently, the transmission of the pain impulse undergoes a powerful dual block.
Final 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 transmission pathway is interrupted (blocked), which clinically manifests as the development of profound analgesia — complete elimination of pain sensitivity while maintaining consciousness.
Briefly: answers to topical questions
What specific structure of the midbrain is activated by morphine when initiating descending control?
When initiating descending control, morphine activates the periaqueductal gray matter (central gray matter) of the midbrain. This structure is key to disinhibiting the descending antinociceptive system.
Following the stimulation of opioid receptors and the inhibition of inhibitory GABAergic neurons, impulses are directed to the medulla oblongata. The following structures are activated there:
- Locus coeruleus — the source of noradrenergic pathways.
- Nucleus raphe magnus — the source of serotonergic pathways.
Descending fibers release mediators that exert an inhibitory effect on pain transmission in the spinal cord.
Where exactly are opioid receptors located in the dorsal horns of the spinal cord during the direct inhibitory action of morphine?
During the direct inhibitory action of morphine, opioid receptors are located on the pre- and postsynaptic membranes of neurons in the dorsal horns of the spinal cord.
The precise localization of receptors includes two levels:
- Presynaptic level — terminals of primary afferent axons. Action upon them leads to the blockade of N-type calcium channels and a decrease in the release of pain mediators (substance P and glutamate).
- Postsynaptic level — the membrane of interneurons. Receptor stimulation causes disruption of the postsynaptic membrane depolarization process and inhibition of neuronal activation.
Memorizing the effects in the brain is assisted by the "C-T-P" mnemonic: Cortex (removes anxiety) — Thalamus (changes emotions) — Periaqueductal gray (turns on descending inhibition).
Class and exam questions
Does the sensation of pain persist during the action of opioids on the cortex and thalamus?
Yes, the basic sensation of pain may persist, but morphine completely eliminates its emotional coloring, sparing the patient from fear, anxiety, and suffering.
What specific structure in the midbrain does morphine activate?
Morphine activates the periaqueductal gray matter, which acts as the trigger mechanism for the functioning of descending inhibitory pathways.
How does supraspinal action affect the spinal cord?
Descending pathways activated in the brain transmit signals (involving serotonin and norepinephrine) that massively stimulate the release of enkephalins and inhibit impulse transmission in the dorsal horns of the spinal cord.
What else to study on this topic
- Direct spinal inhibition: effect on pre- and postsynaptic membranes
- Localization of receptors in neurons of the dorsal horns of the spinal cord
- The role of norepinephrine and serotonin in the antinociceptive system
- Endogenous opioids: functions and characteristics of enkephalins
- Mechanism of ascending pain pathway interruption
Master the entire topic in the «Pharmacology» course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Supraspinal action of opioids" and 5,304 more pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 116 video lessons on the subject
Other topics in the "Analgesics" section
Free video lessons: pharmacologyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.