Table 1: Overview of the effects of the neurotransmitter systems found to be altered in fibromyalgia on HPA axis activity and the effects of drugs used in fibromyalgia, targeting these transmitter systems, on HPA axis activity. Information on effects on the sympathetic nervous system is not included, because results are scarce. The specific effect of the transmitters depends on different aspects of HPA axis activity, that is, basal tone and circadian rhythm or acute stress responses. In addition, under conditions of chronic stress, the transmitter effects on the HPA axis are often altered. The table represents a simplistic summary of the evidence found on transmitter actions on HPA axis activity. Despite a vast number of studies, the precise mechanisms of neurotransmitters on HPA axis functioning remain only incompletely understood [52]; transmitter actions depend on receptor subtypes, brain regions, and type of stressor.

Transmitter systemEffect on HPA axis activity in terms ofHPA axis activity under chronic stress*
basal tone and circadian rhythmacute stress responsesEffect of drugs on HPA axis activity*

Serotoninexcitatory (↑) and inhibitory ()excitatory (↑)inhibitory ()excitatory (↑) and inhibitory ()
Noradrenalinexcitatory (↑) and inhibitory ()excitatory (↑)excitatory (↑)excitatory (↑) and inhibitory ()
Dopamineexcitatory (↑)excitatory (↑)excitatory (↑)?
Opioidsexcitatory (↑)inhibitory ()inhibitory ()excitatory (↑)
Glutamate?excitatory (↑)?excitatory (↑) and inhibitory ()
GABAinhibitory ()inhibitory ()excitatory (↑)?
Substance Pinhibitory ()inhibitory ()inhibitory ()?

*Chronic stress as well as drugs have differential effects on basal tone, circadian rhythm, and acute responses to stress but most studies do not differentiate these aspects. Accordingly, this table does not differentiate in these instances.