An Association of Serotonin with Pain Disorders and Its Modulation by Estrogens

Abstract

Ovarian hormones play an important role in pain perception, and are responsible, at least in part, for the pain threshold differences between the sexes. Modulation of pain and its perception are mediated by neurochemical changes in several pathways, affecting both the central and peripheral nervous systems. One of the most studied neurotransmitters related to pain disorders is serotonin. Estrogen can modify serotonin synthesis and metabolism, promoting a general increase in its tonic effects. Studies evaluating the relationship between serotonin and disorders such as irritable bowel syndrome, fibromyalgia, migraine, and other types of headache suggest a clear impact of this neurotransmitter, thereby increasing the interest in serotonin as a possible future therapeutic target. This literature review describes the importance of substances such as serotonin and ovarian hormones in pain perception and illustrates the relationship between those two, and their direct influence on the presentation of the aforementioned pain-related conditions. Additionally, we review the pathways and receptors implicated in each disorder. Finally, the objective was to stimulate future pharmacological research to experimentally evaluate the potential of serotonin modulators and ovarian hormones as therapeutic agents to regulate pain in specific subpopulations.

Serotonergic Neurotransmission System Modulator, Vortioxetine, and Dopaminergic D2/D3 Receptor Agonist, Ropinirole, Attenuate Fibromyalgia-Like Symptoms in Mice

“…FM is a disease that results from the impaired neurotransmission mediated by serotonin and catecholamines [ 40 , 41 , 42 ]. This altered neurotransmission underlies many symptoms of this disease, including chronic pain, mood and sleep disorders, and cognitive decline [ 43 ].…”

Mechanisms of microbial–neuronal interactions in pain and nociception

“…Given the link between visceral pain and depression and anxiety, as commonly seen in patients with IBS, intestinal serotonin signaling may underlie these behaviors. Additionally, the role of serotonin in visceral pain may be sexually dimorphic as estorgens may regulate serotonin reuptake and degradation ( Paredes et al, 2019 ) However, it is unclear how much of a role microbial regulation of serotonin signaling plays in chronic pain diseases. It is possible that faulty tryptophan production by microbes, or lack of microbial species capable of facilitating ECC secretion of serotonin may contribute to increased visceral pain phenotypes.…”

Modular Characteristics and Mechanism of Action of Herbs for Endometriosis Treatment in Chinese Medicine: A Data Mining and Network Pharmacology–Based Identification

“…Estrogen pathway is related to apoptosis and neural and inflammatory regulatory pathways. Estrogen also play an important role in the regulation of the central serotoninergic system in pain (Paredes et al, 2019). Aromatase is considered a key therapeutic target for regulating the biosynthesis of local estrogen in endometriosis.…”