Vertical Organization of the System
The anti-pain and nociceptive (pain) systems have a clear vertical hierarchy consisting of five main anatomical levels. Each level performs a specific task in pain perception or suppression:
- Cerebral cortex. The highest center where the final perception of pain occurs and its emotional assessment is formed.
- Thalamus. Acts as a sensory relay station, gathering all incoming information and routing pain impulses directly to the cortex.
- Midbrain. Contains the key structure for endogenous analgesia — the periaqueductal gray (PAG) (also known as central gray matter).
- Medulla oblongata. Houses critical reticular formation nuclei. These include the locus coeruleus (source of descending noradrenergic pathways) and the nucleus raphe magnus (source of serotonergic pathways).
- Spinal cord. The level of the dorsal horns (posterior horns) serving as the primary site for switching incoming peripheral pain impulses.
Ascending Pain Pathway
To understand how analgesia works, one must examine the mechanism of afferentation (pain signal transmission).
Pain impulses originate in the periphery and enter the dorsal horns of the spinal cord. Here, primary relay occurs to ascending neural pathways. Signals ascend via these pathways to the thalamus, and from there project to the cerebral cortex.
The primary function of this ascending pathway is the generation of the sensation of pain itself (perception) and its emotional coloring. Under normal conditions, signal transmission proceeds unhindered; however, upon administration of analgesics (e.g., morphine blockade), this pathway is interrupted.
Mechanism of Descending Inhibition
The antinociceptive system operates strictly in a top-down manner. It is activated to block incoming pain impulses at the spinal cord level.
Descending endogenous analgesia occurs in several stages:
- Activation. Neural impulses from the periaqueductal gray in the midbrain travel downward to structures in the medulla oblongata.
- Modulation. In the medulla, these impulses activate neurons of the locus coeruleus and nucleus raphe magnus.
- Effector phase. Activated descending fibers reach the dorsal horns of the spinal cord, releasing inhibitory neurotransmitters — norepinephrine (NE) and serotonin (5-HT).
- Pain blockade. These neurotransmitters act on specialized interneurons, which in turn release enkephalins (ENK) — endogenous opioid peptides. Enkephalins bind to opioid receptors and reliably inhibit further propagation of the pain signal.
Neurochemical Organization
A specific set of neurotransmitters and receptors is involved in transmitting and modulating pain signals.
To suppress pain, the body utilizes norepinephrine and serotonin to provide descending inhibition. Direct blockade is carried out by enkephalins. Opioid receptors, which bind enkephalins (and exogenous opiates), are localized not only in the spinal cord but also at other levels of the pain system, including the thalamus and midbrain.