The description of small fiber neuropathy in a subgroup of fibromyalgia patients supports the disease neuropathic-autonomic underpinning. However, others claim that small fiber neuropathy occurs only in small groups of those with fibromyalgia. Autonomic nervous system
Some suggest that fibromyalgia is caused or maintained by a decreased vagal tone, which is indicated by low levels of heart rate variability, signaling a heightened sympathetic response. Accordingly, several studies show that clinical improvement is associated with an increase in heart rate variability. Some examples of interventions that increase the heart rate variability and vagal tone are meditation, yoga, mindfulness and exercise. Neurotransmitters
Some neurochemical abnormalities that occur in fibromyalgia also regulate mood, sleep, and energy, thus explaining why mood, sleep, and fatigue problems are commonly co-morbid with fibromyalgia. Serotonin is the most widely studied neurotransmitter in fibromyalgia. It is hypothesized that an imbalance in the serotoninergic system may lead to the development of fibromyalgia. There is also some data that suggests altered dopaminergic and noradrenergic signaling in fibromyalgia. Supporting the monoamine related theories is the efficacy of monoaminergic antidepressants in fibromyalgia. Neurophysiology
Neuroimaging studies have observed decreased grey matter of the default mode network in people with fibromyalgia. These deficits are associated with pain processing. Neuroendocrine system
Studies on the neuroendocrine system and HPA axis in fibromyalgia have been inconsistent. One study found fibromyalgia patients exhibited higher plasma cortisol, more extreme peaks and troughs, and higher rates of dexamethasone non-suppression. However, other studies have only found correlations between a higher cortisol awakening response and pain, and not any other abnormalities in cortisol.
As of 2018, the only tricyclic antidepressant (TCA) that has sufficient evidence is amitriptyline.For most people with fibromyalgia, the potential benefits of treatment with the serotonin and noradrenaline reuptake inhibitors (SNRI) duloxetine and milnacipran and the TCAs, such as amitriptyline, are outweighed by significant adverse effects (more adverse effects than benefits), however, a small number of people may experience relief from symptoms with these medications. In addition, while amitriptyline has been used as a first line treatment, the quality of evidence to support this use and comparison between different medications is poor. Very weak evidence indicates that a very small number of people may benefit from treatment with the tetracyclic antidepressant mirtazapine, however, for most, the potential benefits are not great and the risk of adverse effects and potential harm outweighs any potential for benefit.The length of time that antidepressant medications take to be effective at reducing symptoms can vary. Any potential benefits from the antidepressant amitriptyline may take up to three months to take effect and it may take between three and six months for duloxetine, milnacipran, and pregabalin to be effective at improving symptoms. Some medications have the potential to cause withdrawal symptoms when stopping so gradual discontinuation may be warranted particularly for antidepressants and pregabalin.There is tentative evidence that the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) appear to be similar. SSRIs may be used to treat depression in people diagnosed with fibromyalgia.Tentative evidence suggests that monoamine oxidase inhibitors (MAOIs) such as pirlindole and moclobemide are moderately effective for reducing pain.