Review: An Association of Serotonin with Pain Disorders and Its Modulation by Estrogens, 2019, Paredes et al

Andy

Andy

Retired committee member
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.
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Open access, https://www.mdpi.com/1422-0067/20/22/5729/htm
 
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It is notable that the narrative review hypothesise that serotonin levels / activation of 5-HT1A receptor is too low, which is not consistent with the various neuroendocrine studies that have suggested normal and occasionally elevated serotonin pathway activity (but the findings of elevated serotonin activity were mostly in men). Likewise various SSRIs have failed to demonstrate efficacy in double blinded trials with CFS patients, for any self reported symptoms including depressive symptoms. This suggests that "low-serotonin" doesn't seem to be a mediator of symptoms, including depression in this group of patients.

The assumption of too little serotonin seems strange since estrogen generally increases serotonin pathway activity. They do mention a single case of a medical condition that was exacerbated by contraceptive hormone therapy, which had a resolution of fatigue after cessation. But the simplest explanation in that case is the fatigue was simply a consequence of the medical condition...

I think that if CFS or ME patients had a noticeable increase in symptoms due to contraceptive medication, we would have been talking about it for a long time.

But they also mention that:
The role of hormones in the pathophysiology of CFS has also been explored. A study comparing blood levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, progesterone, and cortisol in premenopausal females diagnosed with CFS and paired healthy controls found no significant difference between CFS and fatigue-free patients for LH, FSH, estrogens, and progesterone
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Looking at all the prior evidence, I don't see the relevance of the relationship between estrogen and serotonin to CFS...
 
Snow Leopard said:
It is notable that the narrative review hypothesise that serotonin levels / activation of 5-HT1A receptor is too low, which is not consistent with the various neuroendocrine studies that have suggested normal and occasionally elevated serotonin pathway activity (but the findings of elevated serotonin activity were mostly in men). Likewise various SSRIs have failed to demonstrate efficacy in double blinded trials with CFS patients, for any self reported symptoms including depressive symptoms. This suggests that "low-serotonin" doesn't seem to be a mediator of symptoms, including depression in this group of patients.

The assumption of too little serotonin seems strange since estrogen generally increases serotonin pathway activity. They do mention a single case of a medical condition that was exacerbated by contraceptive hormone therapy, which had a resolution of fatigue after cessation. But the simplest explanation in that case is the fatigue was simply a consequence of the medical condition...

I think that if CFS or ME patients had a noticeable increase in symptoms due to contraceptive medication, we would have been talking about it for a long time.

But they also mention that:


Looking at all the prior evidence, I don't see the relevance of the relationship between estrogen and serotonin to CFS...
Click to expand...

Jonas Bergquist found Pregnenolone to be significantly lower in people with ME [OMF funded study - https://let-me.be/e107_files/downloads/the_me_global_chronicle_-_30_-_20181222.pdf].

Not sure if this is relevant to this discussion.
 
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