Dysfunctional neurotransmitter systems in fibromyalgia, their role in central stress circuitry and pharmacological actions on these systems

Abstract

Fibromyalgia is considered a stress-related disorder, and hypo- as well as hyperactive stress systems (sympathetic nervous system and hypothalamic-pituitary-adrenal axis) have been found. Some observations raise doubts on the view that alterations in these stress systems are solely responsible for fibromyalgia symptoms. Cumulative evidence points at dysfunctional transmitter systems that may underlie the major symptoms of the condition. In addition, all transmitter systems found to be altered in fibromyalgia influence the body's stress systems. Since both transmitter and stress systems change during chronic stress, it is conceivable that both systems change in parallel, interact, and contribute to the phenotype of fibromyalgia. As we outline in this paper, subgroups of patients might exhibit varying degrees and types of transmitter dysfunction, explaining differences in symptomatoloy and contributing to the heterogeneity of fibromyalgia. The finding that not all fibromyalgia patients respond to the same medications, targeting dysfunctional transmitter systems, further supports this hypothesis.

Figure 1

Alterations in transmitter systems found in fibromyalgia patients in terms of increased or decreased activity and action of drugs used in fibromyalgia on these transmitters systems in terms of activity increase or decrease. *The positive effect of naltrexone, an opioid antagonist, on fibromyalgia symptoms is suggested to be mediated through disinhibiting effects on HPA axis activity, rather than by its effect on the opioid system (cf. [–18]).