Opioid drugs enhance the analgesic effect of endogenous opioids by mimicking their action; these molecules of a peptide nature perform different functions at the central level:
- they exercise an inhibitory control of the painful stimulus;
- they modulate the gastrointestinal and endocrine functions and those of the ortho and parasympathetic autonomic system;
- they regulate the emotional and cognitive sphere.
Endogenous opioids derive from macropeptides subjected to enzymatic hydrolysis processes; there are three types of opioids: enkephalins, endorphins and dynorphins.
In order to understand the mechanism of action of these drugs it is essential to know in detail the receptors on which endogenous and exogenous opioids act; there are three receptor types with which opioids interact, following an order of affinity and selectivity.
- Μ receptor: it is the most numerous receptor at the supra-spinal level, but we also find it in the spinal cord area, so as to allow ubiquitous pain modulation. The main functions of this receptor consist in controlling: the analgesic effect at the supra-spinal and spinal levels, the sedative effect, although not in all species; reduced gastrointestinal motility due to inhibition of acetylcholine release; of the release of hormones and neurotransmitters.
- Δ receptor: also located at the supra-spinal and spinal levels: it is responsible for the modulation of analgesia in the respective supra-spinal and spinal areas, and for neuro-endocrine control.
- Κ receptor: same collation as δ receptor, but with different function; the κ receptor is responsible for the psychomimetic effects and for the reduced gastrointestinal motility.
All three types of receptors have the same mechanism of action: they are inhibitory receptors linked to the G protein: once activated, they inhibit the enzyme adenylate cyclase with a consequent reduction in the production of cyclic AMP and the entry of calcium ions, so as to determine an "inhibition of the cell's excitability". This cellular inactivity results in a lower release of neurotransmitters: at the post-synaptic level, the release of potassium ions increases, which reduces the reactivity of the receptor at the post-synaptic level towards the neurotransmitter.
Opioids, endogenous or exogenous, inhibit the transmission of the painful stimulus by acting at various levels: they reduce the perceptive capacity of nociceptors; at the level of the spinal horns, they reduce the release of neurotransmitters responsible for pain transmission; at the thalamic level they prevent the transmission of the painful stimulus to the sensory cortex: on the other hand, they enhance the inhibitory control of the descending modulatory pathways.
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