Ketamine is a dissociative anesthetic and powerful analgesic. At low doses, ketamine can desensitize the central pain pathway and modulate opioid receptors. Studies have generally found that preoperative use of ketamine can reduce opioid consumption by approximately 50% and sub-anaesthetic doses of it have a rapid antidepressant effect, especially refractory depression. Studies have confirmed that esketamine, the S(+) enantiomer of ketamine, has a stronger affinity for NMDA receptors, which can achieve the same effect at smaller doses. While the incidence of neuropsychiatric side effects is significantly lower. On March 4, 2019, the U.S. Food and Drug Administration (FDA) first approved esketamine nasal spray with a new mechanism of action for the treatment of adult patients with refractory depression. Based on the analgesic and antidepressant effects of ketamine, the investigators speculate that esketamine may be effective for patients with chronic visceral pain comorbid depression. At present, the research evidence in this area is relatively lacking. Therefore, this study aims to explore the difference in the efficacy and safety of esketamine as an adjuvant therapy and positive control drug-pregabalin in patients with chronic visceral pain comorbid depression.

Detailed Description: According to the inclusion criteria and exclusion criteria, select patients with chronic visceral pain comorbid depression.

Filtering and grouping period: During this phase, the patient will sign an informed consent form, and then conduct a structured clinical evaluation to determine whether it meets the "depressive disorder" in the DSM-IV-TR diagnostic criteria. According to the ICD-11, determine whether the patients have chronic visceral pain.

Acute treatment period: Randomize patients into the following treatment groups: intravenous administration of esketamine (3 groups, 0.125, 0.25, 0.50 mg/kg)， and duloxetine is co- administered orally. Pregabalin capsules were administered combined with duloxetine orally.

observation period: After 2 weeks, esketamine treatment was discontinued, and observation was continued for 2 weeks. Maintain duloxetine and pregabalin treatment.

Inclusion Criteria:

1. aged 18 to 55

2. Those who can understand and obey the research plan

3. Sign the informed consent form voluntarily

4. Those who meet the DSM-IV-TR depression diagnostic criteria and have first or second episodes of depression

5. Hamilton Depression Scale score ≥ 14 points

6. Those who meet the ICD-11 pain diagnostic criteria, and visual analogue scale score ≥ 7 points. Those who have chronic visceral pain instead of cancer pain.

7. No systemic use of antidepressants and analgesics within 2 weeks after enrollment.

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Exclusion Criteria:

1. Female patients who are pregnant, breastfeeding, or preparing to conceive

2. Allergic to duloxetine or pregabalin in the past.

3. A history of serious or unstable physical diseases, such as cardiovascular/liver/kidney/respiratory/ endocrine/nervous/ blood system disease.

4. A history of epileptic seizures or brain injury, or any neurological disease (including multiple sclerosis, degenerative diseases such as acute lateral sclerosis, Parkinson's disease and movement disorders, etc.);

5. In the last 12 months, the patient has the following medical history or its main diagnosis (DSM-IV-TR) is organic mental disorder, schizophrenia, schizoaffective mental disorder, delusional mental disorder, indeterminate mental disorder, Bipolar disorder, psychotic characteristics that are coordinated or uncoordinated with the mood, and history of substance abuse (including alcohol, psychoactive substances, etc.).

6. Patients with a history of adverse reactions to multiple drugs.

7. The patient is taking psychotropic drugs, including benzodiazepines, sleeping pills, anticonvulsants, etc.

8. During the depressive episode, treatment with at least 2 antidepressants in a sufficient course of treatment or at least one SSRI antidepressant treatment is ineffective. A sufficient dose of treatment means treatment with fluoxetine ≥40 mg/day (or sertraline ≥100 mg/day, paroxetine> 40 mg/day, fluvoxamine> 100 mg/day, citalopram> 40 mg /Day, escitalopram> 20 mg/day, venlafaxine> 150 mg/day, duloxetine> 80 mg/day)

9. Received electroconvulsive therapy within 6 months before enrollment.

10. Those who are currently at serious risk of suicide, and a score of 3 or higher in item 3 of the 17-HAMD .

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