Fibromyalgia in Pregnancy: Neuro-Endocrine Fluctuations Provide Insight into Pathophysiology and Neuromodulation Treatment

Abstract

Fibromyalgia (FM) is a chronic pain disorder with unclear pathophysiological mechanisms, which leads to challenges in patient management. In addition to pain, the disorder presents with a broad range of symptoms, such as sleep disruption, chronic fatigue, brain fog, depression, muscle stiffness, and migraine. FM has a considerable female prevalence, and it has been shown that symptoms are influenced by the menstrual cycle and periods of significant hormonal and immunological changes. There is increasing evidence that females with FM experience an aggravation of symptoms in pregnancy, particularly during the third trimester and after childbirth. In this perspective paper, we focus on the neuro-endocrine interactions that occur between progesterone, allopregnanolone, and cortisol during pregnancy, and propose that they align with our previously proposed model of FM pathogenesis based on GABAergic “weakening” in a thalamocortical neural loop system. Based on our hypothesis, we introduce the possibility of utilizing transcranial direct current stimulation (tDCS) as a non-invasive treatment potentially capable of exerting sex-specific effects on FM patients.

Fibromyalgia pathogenesis explained by a neuroendocrine multistable model

“…We have described a theoretical model of FM pathogenesis based on literature data. This new model includes elements from our previous hypothesis of a pain-processing thalamocortical loop [ 18 ], and our previous review of FM in pregnancy [ 21 ]. The model is supported by literature data as follows.…”

“…This is a theoretical study that presents a hypothesis about the biological mechanisms giving rise to a transition leading to the development of the FM syndrome. The hypothesis was based on a literature search on the PubMed database (National Institutes of Health, Bethesda, MD, USA), from inception through September 2023, combined with our previous thalamocortical loop model of FM chronic pain [ 18 ], and our review concerning FM in pregnancy [ 21 ]. The PubMed search was conducted by using as main keywords the names of different gonadal hormones, glucocorticoids, neurosteroids, and endocrine axes, variously combined with each other or with any of the following: “fibromyalgia”, “pain”, “glutamate”, “GABA”, and the names of various glutamate and GABA receptors.…”