Fig. 2

Histamine receptor sensitivity balance theory. The hypothesis is that histamine is a common mediator of CSU and panic disorder. Four types of histamine receptors are present in neurons: H1, H2, H3 and H4. This theory involves the hypothesis that the sensitivity of the four neuron receptors to histamine can be the same or different for many reasons, and two possibilities may be present. A The first possibility presupposes that the normal status is when the sensitivities of the four receptors are equal. Therefore, the responses of receptors to histamine are equivalent, regardless of the level of histamine (2A). Under normal conditions, patients may exhibit urticaria without other neurological symptoms and signs despite elevated histamine levels while maintaining the balance in their neuron responses. If a constitutional imbalance in the sensitivity of histamine receptors is present, the clinical manifestations of neurological, psychological and/or psychiatric disorders (constitutional histamine-mediated syndrome) may develop (2A1 and 2A2). The possible kinds of sensitivity imbalance may occur in many cases due to the combination of receptor types. The clinical manifestations may differ according to the sensitivity among the receptors. Additionally, subjects can possibly adapt to a balanced state among the responses of the receptors to histamine in the normal state (2A3 and 2A4). However, if histamine levels are increased due to pathological conditions, such as allergic responses, anaphylaxis, allergic rhinitis, asthmatic attacks and/or chronic urticaria, the clinical manifestations of neurological, psychological and/or psychiatric disorders may develop due to the unbalanced responses of the four types of neuron histamine receptors (induced histamine-mediated syndrome). Histamine receptor sensitivity may be related to many conditions, including the number of receptors on target cells and gene mutation of the receptors. B The other hypothesis is that the normal status is unequal sensitivities of the four receptors (2B). At the physiological level, the responses of receptors to histamine maintain normal physiological conditions. However, when the histamine level is increased, neurological and psychological symptoms and signs appear. However, these neurological and psychological changes may be normal defense mechanisms. Namely, if a situation such as anaphylaxis occurs and urticaria develops, the subject might focus on their defense response. Therefore, the subject becomes nervous in situations in which anxiety and panic feel like defense mechanisms. Therefore, it may be natural that subjects experience anxiety and have feelings of panic in situations such as anaphylaxis where histamine levels are raised