An unpleasant experience of severe, long-term, repeated pruritus and the deterioration of local skin lesions bring great psychological pressure to patients, and psychological pressure can also directly worsen pruritus symptoms and local skin lesions; scratching can temporarily relieve the unpleasant experience caused by pruritus and get a sense of euphoria. Over time, scratching is no longer just a way for patients to relieve pruritus, but also a way for patients to alleviate other psychological pressure and get euphoria. Therefore, psychological pressure participates in every link of the vicious circle of pruritus and scratching. Pruritic cutaneous diseases is a psychosomatic disease closely related to psychological stress, which has brought great pain to patients both psychologically and physically for a long time. Therefore, starting with regulating emotions and reducing psychological pressure, it will have a good therapeutic effect on pruritus diseases, which can effectively break the vicious circle of psychological pressure of pruritus and scratching[8–9].
Traditional Chinese medicine believes that the liver stores blood, and governs regulating, it likes the smooth movement of qi and hates depression. If being in a bad mood, then the liver qi is stagnated and turns to heat with the passing of time, then the blood will be disturbed. The liver governs the wood, the spleen governs the earth, the liver qi invades spleen, causing spleen deficiency and dampness, and the liver-heat and spleen dampness invades the skin, causing skin pruritus, eczema, dermatitis and other skin diseases. It should be treated by soothing the liver, clearing heat and invigorating the spleen to eliminate dampness. Danzhi Xiaoyao Powder is published in Xue Xinfu's Abstract of Internal Medicine, which is based on the famous prescription "Xiaoyao Powder" plus zhizi and mudanpi, also known as Jiawei Xiaoyao Powder and Bawei Xiaoyao Powder, which has the effect of soothing the liver and relieving depression, invigorating the spleen and Harmonizing Ying-qi, and clearing stagnated heat. It has been followed by doctors of all ages as a classic prescription for the treatment of liver depression and fire syndrome.
In this study, healthy mice were selected for modeling, which can effectively eliminate the effect of factors other than psychological pressure on pruritus symptoms. The results showed that after treatment, the number of scratches in the DZX group was significantly less than that in the WAS group, indicating that Danzhi Xiaoyao Powder could effectively improve the skin pruritus under the influence of psychological pressure.
It is well known that histamine is the most common pruritus mediator, which exists in human basophils and mast cells. Endogenous sensitizing substances secreted by keratinocytes, such as cytokines, amines, neuropeptides and nerve growth factors, can stimulate mast cells to release histamine and cause skin pruritus. Mast cells can also stimulate skin C-nerve fiber receptors to sensitize and cause skin pruritus. Histamine binds to specific receptors in the plasma membrane, such as H1R and H4R, and activates TRPV1, to activate downstream target molecules in sensory neurons, including G protein, phospholipase C, phospholipase A2 and 12-lipoxygenase, which leads to pruritus. The results showed that the level of plasma histamine in the DZX group was significantly lower than that in the WAS group, indicating that Danzhi Xiaoyao Powder could reduce the plasma histamine level in the model mice, suggesting its possible mechanism.
After treatment with Danzhi Xiaoyao Powder, the degree of depression in the model mice was significantly less than that in the WAS group, indicating that Danzhi Xiaoyao Powder could improve the state of depression caused by psychological stress. The author's previous studies have confirmed that changes in mental state can worsen the pruritus symptoms of this model mice, so improving the state of depression is also a possible treatment for pruritus to alleviate the deterioration of psychological stress. Previous studies have shown that the antidepressant mechanism of Danzhi Xiaoyao Powder may be related to the regulation of hypothalamus-pituitary-adrenal (HPA) axis, which can inhibit the abnormal hyperactivity of HPA axis. The authors' previous studies have also confirmed that chronic psychological stress can lead to damage to the HPA axis and delay the peak of corticosterone secretion in plasma. Psychological stress may lead to the change of HPA axis, but the change may be related to the type of stress and other conditions, so the antidepressant effect of Danzhi Xiaoyao Powder and the mechanism of improving pruritus of chronic psychological stress deterioration may be related to the regulation of HPA axis, but the specific mode of action needs to be further explored.
In this study, it was found that there was still a statistical difference in the number of scratches between the DZX group and the CON group, and the scratching times after treatment was still higher than that in the CON group, indicating that Danzhi Xiaoyao Powder only relieved the pruritus caused by the deterioration of chronic psychological pressure, but it still can not be completely cured, which suggests that Danzhi Xiaoyao Powder can not block all the mechanisms of pruritus in the deterioration of chronic psychological pressure. Existing studies have confirmed the existence of a vicious circle of pruritus and psychological stress. Existing studies have shown that the occurrence and deterioration of pruritus are mainly related to nerve conduction pathways and pruritus mediators, and psychogenic pruritus is also one of the causes of pruritus. The authors' previous studies have confirmed that pruritus with worsening psychological stress can be associated with increased mast cells in skin tissue, elevated plasma histamine levels and changes in the HPA axis. In recent years, the research on psychological stress and pruritus has made remarkable progress in the field of neuroscience. Su Xinyu of Shanghai Jiaotong University confirmed by photogenetics that two types of neurons in the ventral tegmental area regulate two different components of pruritus, that is, γ-aminobutyric acid neurons mediate pruritus-induced aversion, while dopaminergic neurons mediate pleasure after scratching. It is suggested that the brain science-related mechanism of pruritus is related to psychological stress. In addition, a study published by Sanders KM et al in 2018 shows that the vicious circle between pruritus and anxiety exists in healthy people, and the central nervous system plays an important role in the relationship between pruritus and anxiety. In this author's further study in 2019, it was found that a subpopulation of amygdala neurons responded to itch stimuli such as histamine. Optogenetic activation of histamine-responsive amygdala neurons affected both scratching and anxiety-like behavior. Pharmacological and non-pharmacological treatments to reduce anxiety showed good antipruritic effects. In the research of modern traditional Chinese medicine, Danzhi Xiaoyao Powder is effective in the treatment of neurodermatitis, chronic eczema and senile skin pruritus, so focusing on emotion and treating skin pruritus from the liver is a recognized treatment for skin pruritus. This study has confirmed that Danzhi Xiaoyao Powder can relieve skin pruritus caused by chronic psychological stress by controlling histamine release and improving depression. However, the related mechanisms of nerve conduction pathway and non-histamine pruritus medium need to be further studied.