Classification position
Globally, all painkillers are divided into two large groups depending on where and how they work: central and predominantly peripheral action.
Centrally acting agents include three categories of drugs:
- Opioid (narcotic) analgesics. Within this group, pure agonists, partial agonists, and agonist-antagonists of opioid receptors are distinguished.
- Non-opioid drugs that possess intrinsic analgesic activity.
- Mixed-action analgesics, which combine both opioid and non-opioid mechanisms.
Three main directions of opioid action
The mechanism of pain suppression upon the administration of narcotic analgesics is based on three critical processes in the central nervous system:
- Blockade of ascending transmission. The drugs interrupt the pathway through which pain impulses travel upward to the brain. This occurs due to impaired signal transmission from primary afferent fibers to interneurons.
- Activation of descending inhibition. The medications enhance the body's own antinociceptive system, which sends inhibitory signals downward to suppress pain.
- Psychological impact. The way a person emotionally assesses pain is altered. The physical sensation itself may remain, but it loses its frightening coloring.
Spinal mechanism: how pain is blocked
At the spinal cord level, the action unfolds in the region of the posterior horns. The process proceeds on two fronts simultaneously:
- Presynaptically (at the axon terminals of primary afferents): N-type calcium channels are blocked. Consequently, the release of key pain mediators — substance P and glutamate — is reduced. As a result, the pain signal simply cannot be properly transmitted to the next neuron.
- Postsynaptically (on the membrane of interneurons): Here, opioid receptors are stimulated, leading to impaired membrane depolarization. The interneuron becomes "insensitive" to excitatory mediators, and the pain conduction pathway is interrupted.
Supraspinal action and cerebral cortex
The supraspinal effect is mediated through the periaqueductal gray matter. Here, opioids work on the principle of "releasing the handbrake":
- The drugs stimulate opioid receptors.
- This suppresses the activity of inhibitory GABAergic neurons (releasing the inhibitory influence).
- As a result, the descending antinociceptive system is disinhibited and powerfully activated.
- Descending pathways travel to the spinal cord and inhibit pain transmission there, using serotonin and norepinephrine as mediators.
At the level of the cortex and higher centers, the drugs eliminate anxiety and fear associated with trauma or disease. A characteristic phenomenon develops: the patient may be aware of the presence of pain, but it ceases to bother them because its negative emotional appraisal completely disappears.
Briefly: answers to topical questions
What types of classifications of opioid analgesics within the group do pharmacology textbooks distinguish?
Within the group, opioid analgesics are classified by their type of receptor interaction and the potency of the induced effect.
- Full agonists possess maximum intrinsic activity and produce the maximum possible effect.
- Partial agonists have intrinsic activity below the maximum, producing a weaker effect than full agonists.
- Agonist-antagonists exhibit mixed action, as they stimulate one subtype of opioid receptors while simultaneously blocking another.
What side effects are characteristic of narcotic analgesics in case of overdose?
An overdose of narcotic analgesics may cause the following effects:
- Respiratory depression.
- Euphoria.
- Analgesia.
Competitive opioid receptor antagonists are used to manage acute intoxication.
The essence of the opioid effect on the cortex can be described by the phrase: "The pain is there, but I don't care." The drug does not completely erase the sensation itself, but it effectively turns off fear and anxiety.
Class and exam questions
How does analgesia differ from general anesthesia?
During analgesia, the patient is fully conscious, and temperature, tactile, and other types of sensitivity are preserved. General anesthesia, by contrast, implies complete loss of consciousness.
Which pain mediators are blocked in the spinal cord?
At the presynaptic level in the dorsal horns of the spinal cord, opioids reduce the release of substance P and glutamate.
What role does GABA play in the supraspinal mechanism?
Opioids inhibit GABAergic interneurons. This removes the natural brake on the descending antinociceptive system, allowing it to actively suppress pain.
What else to study on this topic
- Receptor characteristics: mu, kappa, and delta
- Differences between full and partial agonists
- Mechanism of action of agonist-antagonists
- Centrally acting non-opioid drugs
- Mixed-action analgesics
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