I. Definition of pain Pain is an unpleasant sensory and emotional experience caused by acute or underlying tissue damage or described by these damages. This definition emphasizes that pain is not only a sensory phenomenon, but also a multidimensional phenomenon that includes sensory, affective, 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 time for tissue healing (typically 3 months)”. Most authors, on the other hand, consider chronic pain as pain that lasts longer than 6 months for practical reasons. Chronic pain perception, pain behavior, social functioning situation at work and at home, emotional state, concern about somatic condition and perception. 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 because of the lack of a uniform definition of chronic pain and the difficulty of identifying chronic pain cases. The incidence of chronic pain in the general population is 20% to 45%. Third, the pathological mechanisms of chronic pain The pathological mechanisms of pain include psychological and physiological mechanisms. The duration of chronic pain may be related to the persistent perception of injury and the neurological changes it induces, but most pain researchers agree that psychological or psychiatric factors play a critical role in the onset, development, persistence, or exacerbation of chronic pain. In pain research, it has long been found that the relationship between injurious stimuli and nociception is not a simple response relationship, that stimulus intensity and pain intensity are not identical, and that pain can still originate from non-injurious stimuli, phenomena that suggest a close relationship between pain and psychological processes. Psychological factors influence the nature, intensity, timing, and spatial perception, discrimination, and degree of response to pain, and are reflected in all aspects of pain. The physiological mechanism of chronic pain is very complex, involving the nervous system, neurotransmitters and biochemical substances. Fourth, the characteristics of chronic pain 1, chronic pain as a symptom syndrome, its etiology is very complex, both congenital and acquired, such as infection, metabolic, endocrine, immune and other various causes; it can be caused by both physical diseases and psychiatric diseases; 2, pain often does not correspond to the underlying pathology or there is no explainable organic lesion; 3, its occurrence, development, persistence or aggravation It is closely related to psychological factors such as anxiety, depression, emotional stress, etc.; 4. The site of pain is often not limited to one site, 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. 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 distress in depression are often intertwined and interact with each other. A large number of studies have been conducted in this regard in recent decades, confirming that there is indeed a link between the two, and initially elucidating the incidence, nature and therapeutic implications of the link between chronic pain and depression. I. The incidence of depression in chronic pain The incidence of depression in the chronic pain population is very high, higher than in patients with chronic medical disease, and more than three times that of the general population. In patients with chronic pain, the incidence of clinically diagnosable depression is 30% to 60%, and when only major depression is considered, its incidence is 8% to 50%. The results reported in this literature are very inconsistent, with some researchers suggesting that depression is rare in patients with chronic pain, while others suggesting that all patients with chronic pain are depressed. Significant differences in incidence are clearly related to differences between studies, such as the type and location of pain, the diagnostic criteria used to determine depression and chronic pain, the source of the sample, and the evaluation of depression. Second, the relationship between chronic pain and depression Although it has been recognized for a long time that there is a relationship between chronic pain and depression, there is no definite empirical information about who is the cause and who is the effect, only several etiological hypotheses about the relationship between chronic pain and depression have been proposed. 1. pain-→depression: that is, depression is a direct consequence or an inherent part of the chronic pain experience. An understandable and even desired outcome occurs in a corner of chronic pain patients as a result of chronic pain exposure and the limitations it imposes on their lives. Pain constitutes an important 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 grief process, arguing that this may both lead to a final adaptation but may also often be stalled in a prolonged state of depression.Fishbain et al. comprehensively reviewed the literature on this subject and most of it considered depression as 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-→mediator-→depression: This model of relationship suggests that chronic pain is not a sufficient condition for depression to occur per se, 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 have 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, which is the tendency to view pain and one’s life circumstances as devastating. In addition, specific personal beliefs about pain can also mediate depressive symptoms of chronic pain. Mediators between chronic pain and depression: ① cognitive, behavioral, and coping styles (e.g., decreased mobility and mental capacity, catastrophizing); ② family and social factors (e.g., dissatisfaction with marriage); ③ anger control (or other negative affect); ④ predisposing qualities (e.g., genetic or developmental psychological); ⑤ medically derived factors (e.g., certain medications, negative attitudes). 3, pain ← – common pathogenic basis – → depression: there may be some common common common pathological mechanisms between chronic pain (especially neuropathic pain) and depressive disorders. 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, hypercortisolism, abnormal dexamethasone inhibition experiments, shortened fast eye movement sleep latency in sleep EEG, and normal or increased endorphin factor I levels in cerebrospinal fluid. Second, antidepressants have a significant therapeutic effect in chronic pain, but the exact mechanism by which these drugs produce their effects is not known. Third, a relatively large number of patients with chronic psychogenic pain appear to have a family history of depression and “depressive spectrum disorders” such as migraine and irritable bowel syndrome, and VonKnorring (1994) et al. suggest that a common pathological mechanism between depressive disorders and chronic psychogenic pain appears to be a disruption of the 5-TH system. Mersky (1994) similarly concluded clinically that “sometimes the brain pathophysiology of pain patients makes them as effective as depressed patients in response to antidepressants, but the difference is that pain patients lack a basis for depressive mood”. 4. Depression-→pain: i.e., chronic pain is explained by implicit depression, and chronic pain is considered as a somatic symptom of depression. Depression is often manifested in some patients, especially in the elderly, as a suspicious subjective narrative about pain and somatic symptoms without emotional problems. Pain as a symptom of depression can be mediated by many psychological and/or physiological mechanisms, including anxiety, tension, excessive preoccupation with the somatic body, and biochemical changes. Depressed patients tend to hide emotional problems behind pain problems for a number of reasons, such as the desire to avoid a diagnosis of psychosis and the idiosyncratic influence of social and cultural constants. 5. Pain-→depression-→more pain: Once pain is present, the coexisting depression significantly affects its subsequent development, regression, etc. Chronic pain and depression interact through a recurrent vicious cycle in which pain increases unpleasant emotions and promotes the memory of unpleasant events, which, in turn, help to induce pain.Fields (1991) proposed a neurobiological model that suggests that depression directly affects pain sensory transmission by increasing the somatic foci that can activate pain-prone neuropilots, and that pain about Negative cognitions such as catastrophizing mediate the cognitive and affective effects of depression. This model is supported by several authors. Third, antidepressants for chronic pain 1. the need for antidepressant application: the incidence of depression in chronic pain is high, and once depression forms, whether primary or secondary, and regardless of its manifestation, it has a significant adverse effect on the quality of life of pain patients, adding mental suffering to their somatic pain, often exacerbating sleep problems, loss of pleasure and interest in a vicious cycle, and depression Patients experience much more severe emotional distress than physical 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, treating depression or depressive symptoms in chronic pain is of great importance. Treating depression in these patients may reduce the emotional distress of pain, fatigue, sleep disturbances, anxiety, nervousness, and fidgeting, thereby improving the patient’s overall health and quality of life. And these may be beneficial for all aspects of the pain experience itself. Some patients can completely eliminate pain with antidepressant treatment. 2. Mechanism of action of antidepressants: The most commonly used antidepressants for the treatment of chronic pain are tricyclic, such as amitriptyline, doxepin, chlorpromazine, and promethazine, and it has not been proven that those are the most effective ones. 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 direct action on opioid receptors, which is achieved through the following mechanisms: ① inhibition of the recycling of 5-HT, dopamine, and norepinephrine (NE) at synaptic sites, which are neurotransmitters that act on the endogenous opioid system; ② improvement of depressed mood and enhancement of pain tolerance and coping; ③ slight inhibition of prostate synthase; ④ positive effects on tryptophan metabolism; ⑤ their anticholinergic and antihistamine effects. The analgesic effect of tricyclic antidepressants is faster, while their antidepressant effect takes 7∽20 days to take effect. SSRIs have no “analgesic” effect on chronic pain, so their therapeutic effect is relatively poor, but their safety is higher than that of tricyclics, and they are suitable for elderly people and patients with poor physical condition.