(i) Definition of pain Pain is an unpleasant sensory and emotional experience caused by or described in terms of acute or underlying tissue damage. This definition emphasizes that pain is not just a sensory phenomenon but a multidimensional phenomenon that includes sensory, emotional, motivational, environmental, and cognitive components. There is no uniform definition of chronic pain. The International Association for the Study of Pain (IASP) defines it as “pain that lasts longer than the normal tissue healing time (usually 3 months)”. Most authors, on the other hand, consider pain lasting longer than 6 months to be chronic pain from a practical point of view. (i) Chronic pain perception, pain behavior, social functioning situation at work and at home, emotional state, concern for somatic conditions and cognition. (ii) Epidemiology of chronic pain Chronic pain is a relatively common problem in the population and is one of the most common reasons for people to seek medical care. Knowledge of the epidemiology of chronic pain is limited due to the lack of a standardized definition of chronic pain and the difficulty in identifying cases of chronic pain. The prevalence of chronic pain in the general population is 20% to 45%. (C) Pathologic mechanisms of chronic pain The pathologic mechanisms of pain include psychological and physiologic mechanisms. The duration of chronic pain may be related to persistent injurious perceptions and their induced neurological changes, but most pain researchers agree that psychological or psychiatric factors play a key role in the onset, development, persistence, or exacerbation of chronic pain. In the study of pain, it has long been found that the relationship between injurious stimuli and nociception is not a simple responding relationship, that stimulus intensity and pain intensity do not coincide, and that pain can yet originate from non-injurious stimuli, phenomena that suggest a close relationship between pain and psychological processes. Psychological factors have an impact on the nature, intensity, temporal and spatial perception of pain, discrimination and degree of response, and are reflected in all aspects of pain. The physiological mechanism of chronic pain is very complex, involving various nervous systems, neurotransmitters and biochemical substances. (D) the characteristics of chronic pain 1, chronic pain as a symptomatic syndrome, its etiology is very complex, both congenital and acquired, such as infection, metabolism, endocrine, immune and other causes; can be caused by physical diseases, but also can be caused by mental illness. 2.Pain is often incompatible with the underlying lesion or there is no explainable organic lesion. 3, its occurrence, development, persistence or aggravation and psychological factors such as anxiety, depression, emotional stress and so on closely related. 4.The site of pain is often not limited to one place, but can be multiple sites. The most common site of chronic pain is the head, followed by the lumbosacral region. 5, its manifestation is mostly persistent dull pain, but also irregular fluctuations. Second, depression and chronic pain Pain and depression are considered to be the most severe forms of human suffering. Clinical experience has shown that somatic pain and emotional pain in depression are often intertwined and interact with each other. A great deal of research has been conducted on this in recent decades, confirming that there is indeed a link between the two, and initially elucidating the incidence, nature, and therapeutic significance of the link between chronic pain and depression. (I) Incidence of depression in chronic pain: The incidence of depression is very high in the chronic pain population, higher than in patients with chronic medical diseases, and more than three times higher than in the general population. The incidence of clinically diagnosable depression in patients with chronic pain is 30% to 60%, and 8% to 50% when only major depressive disorder is considered. The results reported in the literature in this area are very inconsistent, with some researchers suggesting that very few chronic pain patients are depressed, while others suggest that all chronic pain patients are depressed. Significant differences in incidence are clearly related to differences between studies, such as the type and location of pain, diagnostic criteria used to determine depression and chronic pain, the source of the sample, and the evaluation of depression. (ii) Relationship between chronic pain and depression Although it has been recognized that there is a relationship between chronic pain and depression for a long time, there is no definitive empirical information on who is the cause and who is the effect, and only several etiological hypotheses about the relationship between chronic pain and depression have been proposed. 1, Pain -→ depression: i.e., depression is a direct consequence or inherent part of the experience of chronic pain. A corner of chronic pain sufferers as an understandable and even desired outcome that occurs as a result of chronic suffering from pain and the limitations it imposes on their lives. Pain constitutes a significant somatic and psychological stressor that may induce or exacerbate mental distress. Hendler describes in detail the psychological response to chronic pain in terms of the formation of a multi-stage grieving process, arguing that this may lead both to final adaptation but may also often be blocked in a prolonged state of depression.Fishbain et al. provide a comprehensive review of the literature on this subject, most of which considers depression to be a consequence of chronic pain. Nevertheless, the hypothesis of a direct relationship between the two still leaves an unanswered question as to why depression occurs in only a fraction of pain patients. 2. Pain -→ mediators -→ depression: this model of the relationship suggests that chronic pain itself is not a sufficient condition for the occurrence of depression, but is mediated by some cognitive behaviors associated with it, causing increased levels of depression. When the impact of pain on perception and life is controlled for, the link between pain and depression is practically non-existent. Some patients with chronic pain often experience significant cognitive distortions and feelings of helplessness, such as the impact of pain on their lives as perceived by the patient, the corresponding decrease in social rewards, the resulting decrease in activities, and the decrease in self-control and self-practice. Certain specific pain coping behaviors are clearly associated with depression. One of these is catastrophizing, i.e., the tendency to view pain and one’s life circumstances as devastating. In addition, specific personal beliefs about pain can mediate depressive symptoms in chronic pain. Mediators between chronic pain and depression: ① cognitive, behavioral, and coping styles (e.g., decreased mobility and spirituality, catastrophizing); ② family and social factors (e.g., marital dissatisfaction); ③ anger control (or other negative affect); ④ predisposing qualities (e.g., genetic or developmental psychological); and ⑤ medical factors (e.g., certain medications, negative attitudes). 3, pain ← – common pathogenic basis – → depression: chronic pain (especially neo-inflammatory pain) and depressive disorders may have some common common pathological mechanisms. First, biological similarities between the two include low melatonin levels in serum and urine, low 5-HIAA in cerebrospinal fluid, low platelet monoamine oxidase, decreased promethazine (3H) receptor binding capacity, hypersecretion of cortisol, abnormal dexamethasone suppression experiments, shortened fast-eye-movement sleep latency in sleep electroencephalograms, and normal or increased cerebrospinal fluid endorphin factor I levels. Second, antidepressants have a significant therapeutic effect in chronic pain, but the exact mechanism by which these drugs produce their effects is unknown. Third, a relatively large number of patients with chronic cardiac pain appear to have a family history of depression and “depressive spectrum disorders” such as migraine and irritable bowel syndrome, and von Knorring (1994) and others have suggested that the common pathogenesis between depressive disorders and chronic cardiac pain appears to be a disorder of the 5-TH system. Mersky (1994) clinically similarly argued that “sometimes the brain pathophysiology of pain patients makes them as effective on antidepressants as depressed patients, unlike pain patients who lack a basis for depressed mood”. 4, depression – → pain: that is, the use of implicit depression to explain chronic pain, chronic pain is considered to be a physical symptom of depression. Depression is often manifested in some patients, especially the elderly, as a hypochondriacal master narrative about pain and somatic symptoms without emotional involvement. Pain as a symptom of depression can be mediated by a number of psychological and/or physiological mechanisms, including anxiety, tension, excessive preoccupation with the body, and biochemical alterations. There are many reasons why depressed patients tend to hide emotional problems behind pain problems, such as the desire to avoid a psychiatric diagnosis and the idiosyncratic influence of social and cultural norms. 5. Pain -→ depression -→ more pain: once pain is present, the co-existence of depression can significantly influence its subsequent development, regression, etc. Chronic pain and depression interact with each other through a recurrent vicious cycle in which pain increases unpleasant affect and promotes the remembering of unpleasant events, which, in turn, contribute to the triggering of pain.Fields (1991) proposed a neurobiological model that suggests that depression directly affects the sensory transmission of pain by increasing the number of somatic foci that can activate labile pain neurons, and that negative perceptions about the pain negative cognitions about pain such as catastrophizing mediate the effects of depression on cognitive and affective aspects. This model is supported by several authors. (C) Antidepressants in the treatment of chronic pain 1. Necessity of antidepressant application: depression has a high incidence in chronic pain and, once it has developed, whether primary or secondary, and regardless of its manifestations, it has a markedly adverse effect on the quality of life of the pain patient, adding mental suffering to his or her somatic pain, often in a vicious circle of exacerbation of sleep problems, loss of pleasure and interest, and Depressed patients experience much more severe emotional pain than somatic pain. Depression is one of the most serious problems in chronic pain, and about 50% of patients are admitted to the hospital because they feel helpless and have thoughts of dying. Therefore, it is important to treat depression or depressive symptoms in chronic pain. Treating depression in these patients reduces the emotional distress of pain fatigue sleep disturbances anxiety nervousness and restlessness and thus improves the overall health and quality of life of the patient. And these may be beneficial to aspects of the pain experience itself. Some patients with antidepressant treatment can completely eliminate pain. 2, the mechanism of action of antidepressants: the most commonly used antidepressants for the treatment of chronic pain are tricyclic, such as amitriptyline, doxepin, chlorpromazine, promethazine, has not yet been proved that these kinds of that one is the most effective. The doses used in the treatment of chronic pain are much smaller than those used in antidepressant therapy. In addition to their pharmacological properties of sedation, anxiolysis, and cognitive improvement, antidepressants have an additional “sedative” effect without having a direct effect on opioid receptors, which is mediated by the following mechanisms: (1) Inhibition of the recycling of 5-HT, dopamine, and norepinephrine (NE) at the synaptic site. opioid system. (ii) Improvement of depression and enhancement of pain tolerance and coping. (iii) Slight inhibitory effect on prostate synthase. ④ Positive effects on tryptophan metabolism. ⑤ Its anticholinergic and antihistamine effects. The analgesic effect of tricyclic antidepressants appears faster, while its antidepressant effect takes 7~20 days to be effective. SSRI does not have “analgesic” effect on chronic pain, so its therapeutic effect is relatively poor, but its safety is higher than that of tricyclic drugs, and it is suitable for the elderly and the patients with poor physical condition.