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.
Highlights
Pain is subjective by definition and the treatment of pain is complex since its perception is influenced by neurobiological and psychological factors as well as by social-cultural differences and the hormonal behavior of each individual [1]
A positron emission tomography (PET) scan study in postmenopausal women showed an increase by 21% on the binding of altanserin to the receptors when women were treated with transdermal estrogen and micronized progesterone [31]
A study comparing blood levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, progesterone, and cortisol in premenopausal females diagnosed with chronic fatigue syndrome (CFS) and paired healthy controls found no significant difference between CFS and fatigue-free patients for LH, FSH, estrogens, and progesterone, CFS-diagnosed patients were shown to have significantly lower levels of cortisol [154]
Summary
Pain is subjective by definition and the treatment of pain is complex since its perception is influenced by neurobiological and psychological factors as well as by social-cultural differences and the hormonal behavior of each individual [1]. It is crucial to understand the causes, pathophysiology, and different targets of therapies of pain as pain is highly prevalent in the global population. Based on the analysis of the morbidity and mortality weekly report of the Center for Disease and Prevention Control (CDC) in 2016, an estimated 20.4% of adults in the U.S suffered from chronic pain and among these, 8% had high-impact chronic pain [2]. Chronic pain is one of the principal reasons adults seek medical care; is the cause of a high disability index, and is closely linked with the opioid abuse epidemic [2]. The impact of chronic pain affects the individual’s quality of life, but is responsible for the increase of disability-adjusted life years (DALY), a negative marker of overall health and life expectancy in the society [4,5,6,7]
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