Brain Smooth Muscle Axis: A Hypothesis and Its Interrelation with Comorbid Depression or Traditional Chinese Medicine Theory of Gan-Shicangxue and -Shishuxie

Brain-smooth muscle (BSM) axis refers to a bidirectionally influencial and modulatory pathway between the encephalic region and smooth muscle. Via a local cytochrome P450 enzyme and an endogenous active material, stress reaction between the brain and vascular or visceral smooth muscle was modulated, specially implicated depressive comorbidities. Evidence provided by publications and recent experiments of this research group showed that firstly, 40%–50% depression is comorbidity of functional gastrointestinal disorders; a frequent comordibity of functional hypothalamus amenorrhea and depression; depression increases 3- to 6-fold of nocturia than in healthy people; myocardial and cerebral ischemia induce depression. Comorbidity just mentioned especially refers to simultaneous disorders of the brain and vascular or visceral smooth muscle. Secondly, a traditional Chinese medicine formula is as effective as an anti-depressive, prokinetic and vasoactive, which highlights the therapeutic mechanism of modern anti-depressive serotonin and noradrenaline reuptake inhibitors. Absorbed bioactive compounds in hippocampus, intestine and vessel wall were detected after oral administration of the formula and forced swimming rat. Thirdly, both sides of the BSM axis are the same, suggesting the common pathophysiological mechanism. Among the four axes, only “brain”, one side of the axis, is the same and the other sides are different. Fourthly, the pivotal role is that one of the important pathogenetic mechanisms involved in liver visceral manifestation of TCM theory and stress disease is the disorder of the BSM axis. The validation and improvement of the BSM axis hypothesis contribute much to the study of depression, stress diseases and liver visceral manifestation in TCM.