Review: 5-HT1, 5-HT2, 5-HT3 and 5-HT7 Receptors and their Role in the Modulation of Pain Response in the Central Nervous System

Abstract

Background:The aim of this review was to identify the mechanisms by which serotonin receptors involved at the central level are able to modulate the nociceptive response. Pain is a defense mechanism of the body that entails physio-logical, anatomical, neurochemical, and psychological changes, and is defined as an unpleasant sensory and emotional expe-rience with potential risk of tissue damage, comprising the leading cause of appointments with Physicians worldwide. Treatment for this symptom has generated several neuropharmacological lines of research, due to the different types of pain and the various drugs employed to treat this condition. 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).Method:In this review, a search was conducted on PubMed, ProQuest, EBSCO, and the Science Citation Index for studies evaluating the effects of 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS on the modulation of different types of pain.ConclusionWe concluded that 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS modulate the pain, but this depends on the distribution of the receptors, dose of agonists or antagonists, administration route, pain type and duration in order to inhibit, excite, or even maintain the nociceptive response.

Contribution of central sensitization to stress-induced spreading hyperalgesia in rats with orofacial inflammation

“…Active 5-HT-dependent descending pathway from the RVM plays a key role for the maintenance of persistent pain after tissue and nerve injury [ 6 , 35 , 36 ]. Spinal 5-HT 3 receptors widely existing in the dorsal horn of spinal cord have been reported to mediate descending serotonergic facilitation and the upregulation of 5-HT 3 receptor expression in the dorsal horn presents enhanced descending pain facilitation after tissue and nerve injury [ 6 , 37 , 38 ]. Some studies have realized the important role of peripheral 5-HT 3 receptors in functional pain syndromes such as TMD and FMS [ 39 , 40 ].…”

Pharmacological interaction between NSAIDS with clomipramine and risperidone in mice visceral pain

“…Nociception is a complex condition controlled by diverse neuromodulators including the monoaminergic systems noradrenaline (NA), 5‐hydroxytryptamine 5‐HT), and dopamine (DA) have diverse modulatory roles in pain signaling. (Bannister & Dickenson, ; Bannister, Kucharczyk, & Dickenson, ; Cortes‐Altamirano et al, ). Therefore, the possibility of drugs that modify the monoaminergic system, such as clomipramine or risperidone, could enhance antinociception activity of NSAIDs.…”

Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy

“…Serotonin (5-HT), as an important neurotransmitter, could effectively modulate the nociceptive response and serve as a special regulator in NP. When 5-HT acts on its receptors, 5-HT 1 receptor activation create a hyperpolarizing effect; while 5-HT2 and 5-HT3 activation leads to primary nociceptive neurons depolarized in DRG [ 80 ] (Fig. 2 ).…”