The main symptoms of depression as we know it are sadness, lack of interest, guilt, self-blame, and suicide, but there are actually many other symptoms, pain being one of them. However, pain is the most overlooked and misdiagnosed symptom in the diagnosis of depression, precisely because the symptoms of this type of depression mostly start with pain (back pain, headache, etc.) or affect social function, and are often seen in neurology, orthopedics, pain medicine, etc. This not only wastes medical resources, but also delays the patient’s condition and misses the opportunity for early diagnosis and treatment. Depression and pain are closely related: There are two major neurotransmitters in the body, namely 5-hydroxytryptamine and norepinephrine, which are closely related to the occurrence and treatment of depression and pain. Depression occurs when the 5-hydroxytryptamine and norepinephrine systems are hypofunctioning. Increasing 5-hydroxytryptamine and norepinephrine system function or the concentration of 5-hydroxytryptamine and norepinephrine in the synaptic gap may suppress central pain. This shows that pain symptoms and depressed mood are neurobiologically closely related, which explains why depressed patients develop painful somatic symptoms; 5-hydroxytryptamine reuptake inhibitor class antidepressants are effective in improving depressed mood; clinical studies confirm that norepinephrine reuptake inhibitor class antidepressants are effective in both improving depressed mood and relieving painful somatic symptoms associated with depression symptoms. Studies have shown that the prevalence of somatic pain symptoms in depressed patients is 65%; 43.4% of patients with major depression have more than one chronic somatic pain symptom, including back, gastrointestinal, joint and limb pain and headache, and its severity is positively correlated with the severity of depression. This suggests that when we encounter unexplained painful somatic symptoms, we should think that such pain is likely to be a “signal” of depression, and also reminds doctors in other departments that if patients complain of “pain” but no somatic disease can be identified as the cause of the pain If a patient complains of “pain” but no physical illness is identified as the cause of the pain, the patient should be promptly advised to seek psychiatric consultation to rule out depression as the cause. Therefore, it is recommended that non-specific pain with no clear cause may be a “sign” of depression, and it is advisable to go to a psychiatrist for further diagnosis to avoid misdiagnosis and mistreatment!