Classification in Pharmacology
Globally, all analgesics are divided into two major groups based on their site and mechanism of action: central-acting and predominantly peripheral-acting agents.
Central-acting agents include three main categories:
- Opioid (narcotic) analgesics. This group is further subdivided into pure agonists, partial agonists, and agonist-antagonists of opioid receptors.
- Non-opioid agents with intrinsic analgesic activity.
- Mixed-mechanism analgesics, which combine both opioid and non-opioid mechanisms.
Three Main Mechanisms of Opioid Action
The pain-suppressive mechanism of opioid analgesics is based on three critical processes in the central nervous system:
- Blockade of ascending transmission. The drugs interrupt the pathway carrying pain impulses upward to the brain. This occurs by disrupting signal transmission from primary afferent fibers to interneurons.
- Activation of descending inhibition. The drugs enhance the body's own antinociceptive system, which sends inhibitory signals downward to suppress pain.
- Effects on the psyche. The emotional appraisal of pain is altered. The physical sensation itself may persist, but it loses its frightening affective quality.
Spinal Mechanism: How Pain is Blocked
At the level of the spinal cord, action unfolds in the dorsal horns via two distinct fronts:
- Presynaptically (at primary afferent axon terminals): N-type calcium channels are blocked. This decreases the release of key pain mediators — substance P and glutamate. As a result, the pain signal fails to properly transmit to the next neuron.
- Postsynaptically (on interneuron membranes): Opioid receptors are stimulated here, leading to membrane hyperpolarization. The interneuron becomes resistant to excitatory neurotransmitters, interrupting the pain conduction pathway.
Supraspinal Action and the Cerebral Cortex
Supraspinal effects are mediated primarily through the periaqueductal gray (PAG). Here, opioids function by "releasing the brake":
- The drugs stimulate opioid receptors.
- This inhibits GABAergic inhibitory neurons (removing tonic inhibition).
- Consequently, the descending antinociceptive system is disinhibited and powerfully activated.
- Descending pathways project to the spinal cord, inhibiting pain transmission using serotonin and norepinephrine as neurotransmitters.
At the level of the cerebral cortex and higher centers, the drugs alleviate anxiety and fear associated with trauma or disease. A characteristic phenomenon develops: the patient may perceive the presence of pain, but it no longer distresses them because its negative emotional appraisal is completely abolished.