Serotonin (5-hydroxtryptamine [5-HT]) in the central nervous system (CNS) has long been associated with pain processing and modulation. 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems.
- Serotonin (5-hydroxytryptamine) is a monoamine acting as one of the neurotransmitters at synapses of nerve cells.
- Serotonin receptors are G-protein-coupled receptors (GPCRs).
- Serotonin acts through several receptor types and subtypes. It has a role in the etiology of several diseases, including depression, schizophrenia, anxiety and panic disorders, migraine, hypertension, pulmonary hypertension, eating disorders, vomiting and irritable bowel syndromes.
- Serotonin [5- HydroxyTryptamine (5-HT)] is a neurotransmitter with seven families (5-HT1-5-HT7) and approximately 15 receptor subtypes.
- Serotonin modulates neuronal activity; however, this neurotransmitter is related with a number of physiological processes, such as cardiovascular function, gastric motility, renal function, etc. On the other hand, several researches reported that serotonin modulates nociceptive response through 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the Central Nervous System (CNS).
- Estrogen can modify serotonin synthesis and metabolism, promoting a general increase in its tonic effects.
¶ Serotonin and cardiovascular disease
- 5-HT2 receptors are mediators of the biological responses of vessels and blood platelets to 5-HT.
- The importance of 5-HT in peripheral and cerebral ischemia is shown by the key role it plays in inducing vasoconstriction, platelet aggregation, vascular permeability, and cell proliferation.
- Of particular importance is the 5-HT-selective hypersensitivity developing in vessels/platelets shortly after acute ischemia or early in the development of chronic vascular diseases.
¶ Serotonin and depression
- 5-HT deficiency is crucial for the development of depression and that an impaired 5-HT metabolism may play a major role in the development of this disorder.
- Stress is a common etiological factor in the development of depression and the circadian system is highly interconnected to stress-sensitive neurotransmitter systems such as the serotonin (5-hydroxytryptamine, 5-HT) system.
¶ Serotonin and pain
- Serotonin (5-hydroxtryptamine [5-HT]) is present in central and peripheral serotonergic neurons, it is released from platelets and mast cells after tissue injury, and it exerts algesic and analgesic effects depending on the site of action and the receptor subtype.
- After nerve injury, the 5-HT content in the lesioned nerve increases.
- 5-HT receptors of the 5-HT3 and 5-HT2A subtype are present on C-fibers.
- 5-HT, acting in combination with other inflammatory mediators, may ectopically excite and sensitize afferent nerve fibers, thus contributing to peripheral sensitization and hyperalgesia in inflammation and nerve injury.
¶ Serotonin and headaches
- A low central 5-HT disposition associated with an increase in 5-HT released during a migraine attack is the most convincing change of 5-HT metabolism implicated in migraine.
- A low 5-HT state facilitates activation of the trigeminovascular nociceptive pathway, as induced by cortical spreading depression.
- 5-HT is involved in pain progression, which is evident by the use of triptans (serotonin receptor 1B/1D [5-HT1B/1D] agonists) for abortion of acute attacks of migraine and cluster headache.
- 5-HT1B/D/F are related to vasoconstriction. 5HT2 is related to dilatation. During a migraine attack, the vessel is dilated and the level of 5HT is decreased. That is why you want to offer an agonistic effect to 5-HT1B/D/F (such as using a triptan or ditan) or an antagonist effect to 5-HT2 (such as Trazodone).
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