Depression manifests itself in many other symptoms besides sadness, lack of interest, guilt, self-blame, and suicide, and pain is one of them. However, pain is one of the most overlooked and misdiagnosed and underdiagnosed symptoms in the diagnosis of depression. Psychiatrists refer to this as painful somatic symptoms, which are described by a variety of terms, such as chronic painful somatic symptoms, medically unexplained symptoms, and somatization symptoms. It is precisely because the patient’s symptoms manifest as pain (back pain, headache, etc.) that he or she is often seen in neurology, orthopedics, pain medicine, etc., which is not only a waste of medical resources, but also a delay in the patient’s condition and a missed opportunity for early diagnosis and treatment. Pain: a common symptom of mental illness Pain is an extremely common symptom in patients with mental illness, with headache being the most common (Figure 1). The prevalence of headache is 64% in people with mental illness, compared with 48% in the healthy population. In addition, the prevalence of several common pain symptoms, such as muscle pain, stomach pain, and chest pain, was 53%, 51%, and 46%, respectively, in psychiatric patients, but much lower in the healthy population, at 27%, 20%, and 14%, respectively. The study showed that the prevalence of somatic pain symptoms in depressed patients was 65%; in patients with major depression, the prevalence of more than one chronic somatic pain symptom was as high as 43.4%, and common back, gastrointestinal, joint, limb pain and headache, while it was only 16.1% in other patients. Chronic somatic pain was strongly associated with depression and its severity was positively correlated with depression severity (Figure 2). In addition, it has been found that the majority of patients referred to psychiatry or neurology presented with depression with pain, and most of them visited various departments for pain and underwent various tests, but no organic disease was found. This suggests that when encountering this kind of unexplained painful physical symptoms, we should think that this kind of pain may be caused by emotional problems. The results of a survey showed that 49.2% of Chinese patients who consulted a neurologist for nonspecific pain met the current diagnostic criteria for depressive episodes, and 80.7% of them rated their pain as moderately severe, but only 14.2% had received antidepressant treatment in the past 3 months. This shows that non-specific pain bothers a lot of patients, which reminds other doctors, if the patient complains of “pain”, but can not find physical disease, should be promptly recommended to patients to the psychiatric consultation. Depression and pain are closely related There are two major neurotransmitters in the human body, namely, 5-hydroxytryptamine (5-HT) and norepinephrine (NE), which are closely related to the occurrence and treatment of depression and pain. In the human brain, most of the 5-HT bundles originate in the midbrain nucleus accumbens and most of the NE bundles originate in the midbrain nucleus accumbens.5-HT and NE project upward in the brain via the upward pathway and directly stimulate many brain regions, including the cerebral cortex and limbic system. The cerebral cortex (including the prefrontal cortex) is primarily involved in the management of executive functions, and the limbic system (including the hippocampus, anterior cingulate cortex, hypothalamus, and amygdala) is primarily involved in the management of behavior, motivation, and emotion. Depression occurs when the 5-HT and NE systems are low-functioning. In addition, 5-HT and NE project downward to the cristate medulla via the inferior fasciculus and are involved in the regulation of pain, and are key neurotransmitters in the inferior pathway that inhibit pain. Thus, increasing the function of the 5-HT and NE system or the concentration of 5-HT and NE in the synaptic gap may inhibit central pain. Thus, pain symptoms are neurobiologically strongly associated with depressed mood, which explains why depressed patients experience painful somatic symptoms; 5-hydroxytryptamine reuptake inhibitor (SSRI)-based antidepressants are effective in improving depressed mood; and norepinephrine reuptake inhibitor (SNRI)-based antidepressants are effective both in improving depressed mood and in alleviating depression-associated Painful somatic symptoms. Depression and pain interact with each other, and the amygdala is the bridge From the perspective of brain anatomy, depression affects a number of brain regions, such as the insular cortex (the cortex associated with integrating information about sensory experiences to generate emotion), the prefrontal cortex (involved in the management of executive functions, including working memory, decision-making, planning, and judgment), and the anterior cingulate cortex (which plays a role primarily in rational cognitive functions, such as reward expectancy, decision-making, empathy, emotion integration, emotional stimulation, and attention). , emotional integration, emotional stimulation, and attentional functions), the hippocampus (an important site for the formation and storage of associative and emotional memories), and the amygdala (which plays an important role in the formation and memorization of emotional responses). Interestingly, the brain regions affected by depression are also involved in pain perception and processing, and pain stimuli also primarily activate the same brain regions as in depression, including the insular cortex, prefrontal cortex, anterior cingulate cortex, hippocampus, and amygdala, affecting the brain’s processing of pain and emotional responses to pain, where the amygdala is thought to be the bridge between emotion and pain, and negative emotions can enhance amygdala activity, thereby Negative emotions can enhance amygdala activity, thereby enhancing the perception of pain. On the contrary, positive emotions inhibit amygdala activity, thus decreasing the perception of pain. People with depression have organic brain changes Neuroimaging data suggests that depression also causes organic changes in the brain. A series of studies have found that patients with depression have significant decreases in gray matter volume in the hippocampus, amygdala, anterior cingulate cortex, and dorsomedial prefrontal cortex, and that chronic pain also has a toxic effect on the brain, causing gray matter atrophy, with patients with chronic pain experiencing a 5% to 11% decrease in gray matter volume throughout the brain, which is equivalent to 10 to 20 years of normal aging. Studies on brain-derived neurotrophic factor (BDNF) have found that acute or chronic stress and pain can lead to significantly lower levels of BDNF in the hippocampus of mice, and recurrent depression and suicide attempts have been associated with low levels of serum BDNF in humans, which also suggests a correlation between depression and pain. This may partially shed light on why patients with depression experience painful somatic symptoms. Timely Recognition of Pain First, physicians should proactively ask patients about painful somatic symptoms. An epidemiological survey in Asia showed that the incidence of pain in patients with major depression attending specialized hospitals averaged 52%, with a low of 35% in mainland China and a high of 73% in Hong Kong. At present, there are still a considerable number of doctors who believe that there are not many depressed patients with pain symptoms, which may be due to the fact that when patients go to the psychiatric consultation, they themselves do not realize that physical discomfort is actually a manifestation of emotional problems, so they do not take the initiative to complain about it. In addition, not all common painful discomforts in depressed patients are very intuitive, such as tightness in the head associated with muscle tension, stiffness, heaviness, soreness and swelling of the neck and back, etc. Some patients will also have somatic discomforts, such as ants (worms) like sensations under the skin, a feeling of the skin as if it were poured with cold water or hot, a feeling of rising or falling air in the body, a feeling of a foreign body in the digestive tract, dysphagia, etc., or even just a completely indescribable “I don’t feel well all over”, etc. Psychosocial factors play an important role in the occurrence and development of pain. Psychosocial factors affecting pain include early social learning experiences, perception of pain, emotions, personality, cultural background, as well as gender and age. In particular, adverse emotions such as depression, anxiety, and fear often accompany or exacerbate pain. Psychiatrists should proactively ask and carefully identify whether the pain is associated with depression, especially in patients who have had multiple visits to other departments but have not been found to have a physical illness. Second, the patient’s pain symptoms should be clearly diagnosed. Early diagnosis is a prerequisite for early treatment. Most of the patients with physical pain have already been seen in other departments and have undergone relevant examinations, so it is very important to refer to the results of previous examinations and make a clear diagnosis according to the diagnostic criteria of depression. At the same time, the patient should explain why the depressed patient has physical pain. Only when patients recognize the diagnosis of depression will they accept antidepressant treatment and improve treatment compliance. Once again, attention should be paid to the treatment of patients with depression accompanied by pain. Depressed patients with pain somatic symptoms have a great impact on their prognosis, on the one hand, aggravate the patient’s experience of mental pain, make the disease delayed or incurable, increase the risk of relapse and suicide, on the other hand, increase the consumption of unnecessary medical resources. Therefore, once the diagnosis of depression with pain is established, antidepressants should be selected immediately for systemic treatment, with norepinephrine reuptake inhibitor (SNRI)-type antidepressants as the first choice. Studies have confirmed that amitriptyline, doxepin, fluoxetine, and paroxetine, among others, are highly effective for pain symptoms in depression. In general, when depression is cured by antidepressant treatment, pain symptoms will naturally disappear without the need for additional pain medication. Conclusion Pain is one of the common symptoms of depression, which should be of great concern to clinicians, especially those in general hospitals, such as cardiovascular, roentgenology, neurology, orthopedics, etc. If the patient manifests somatic pain but no somatic disease can be detected, the patient should be promptly advised to go to the psychiatry department for consultation. Depressed patients with pain symptoms can seriously affect the patient’s prognosis. Therefore, paying attention to patients’ painful somatic symptoms and effectively treating depression can lead to a real cure for patients, as well as further recovery of social functions and improvement of quality of life.