Patient description: The patient is a 31-year-old woman complaining of abdominal pain. The pain started last night as diffuse abdominal discomfort. She had poor appetite as well as malaise. The pain worsened in intensity and became sharp in the morning. The pain became localized to the right lower quadrant in the morning. The temperature is within the normal limits with normal vital signs. Focal tenderness and guarding were observed during palpation of the right lower quadrant. Palpation of the left lower quadrant causes pain on the right. Her lab work is remarkable for leukocytosis. Computed Tomography of the abdomen with contrast shows the presence of a distended appendix with thickened appendiceal wall without perforation, abscess or gangrene. She is a candidate for laparoscopic appendectomy under general anesthesia.

Clinical trial eligibility criteria: eligible ages (years): 18.0-85.0,  Painful Diabetic Peripheral Neuropathy Female and male patients aged 18-85 years. 2. Patients with a history of type 2 diabetes mellitus according to The American Diabetes Association (ADA). 3. Patients with a diagnosis of painful diabetic peripheral neuropathy (PDPN) caused by type 2 diabetes mellitus based on DN4 ≥4. 4. Patients whose average pain intensity in PDPN in last 24 hours (measured by VAS), evaluated on baseline visit, is equal or more than 40 mm (0 mm ='no pain' and 100 mm ='worst possible pain'). 5. Ability to adhere to trial protocol. 6. Written informed consent. The methods for assessment medical history, interview, completing the DN4 questionnaire, physical examination, assesment of pain on VAS and laboratory analyses  Patients who took PDPN medication and/or analgesics on a day of baseline visit. 2. Patients with a known hypersensitivity to duloxetine, pregabalin, paracetamol or tramadol or any of the inactive ingredients or have any contraindication for the use of duloxetine, pregabalin, paracetamol or tramadol. 3. Patients with a history of inadequate pain response (pain reduced was equal or less than 30%) to: 3.1. pregabalin at maximum allowed treatment daily dose 600 mg, 3.2. duloxetine at maximum allowed treatment daily dose 120 mg, 3.3. venlafaxine at maximum allowed treatment daily dose 375 mg, 3.4. gabapentin on daily treatment dose more than 1800 mg 3.5. amitriptilin at maximum allowed treatment daily dose 150 mg. 4. Patients, who are currently treated with a daily dose that exceeds: 4.1. 150 mg of pregabalin, 4.2. 60 mg of duloxetine, 4.3. 150 mg of venlafaxine, 4.4. 600 mg of gabapentin. 5. Patients with an uncontrolled type 2 diabetes mellitus. 6. The average scores of less than 20 on MoCA. 7. Have any other type of neuropatic pain, contrasted to PDPN. 8. Evidence of another cause of distal polyneuropathy other than diabetic. 9. Have a serious (evaluated by physician) unstable cardiovascular (e.g. uncontrolled hypertension), hepatic, renal, respiratory, ophthalmologic, gastrointestinal, or hematologic illness, symptomatic peripheral vascular disease, malignant disease or other medical condition that could lead to hospitalisation during the course of the trial. 10. Have a diagnosis or history of uncontrolled glaucoma. 11. Known or suspected alcohol or drug abuse or addiction (excluding nicotine and caffeine). 12. Patients with a history of depression (less than one year after completing the last medical treatment), mania, bipolar disorder, psychosis or schizophrenia. 13. Pregnancy, lactation and women of child-bearing potential without highly effective* or at least acceptable** contraception (according to the Recommendations related to contraception and pregnancy testing in clinical trials). 14. Patients with a history of epilepsy, stroke or neurodegenerative disease. 15. Patients taking Monoamine oxidase (MAO) inhibitors or are within one year of their withdrawal. 16. Acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C). 17. Patients with suspected Restless leg syndrome (RLS). 18. Abnormal thyroid-stimulating hormone (TSH) concentrations (according to the references value of the local laboratory). 19. Vitamin B12 and folic acid deficiency (according to the reference values of the local laboratory). 20. Surgical procedures planned to occur during trial (patients may be rescreened following completion of and recovery from the surgical procedure). 21. Concomitant treatment that might influence the final therapeutic effect of the tested active substances including non-medical treatments. 22. Patients who under the opinion of the investigator will not be compliant to the treatment or not be able to finish the trial for any other reason Highly effective contraception is combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation(oral, intravaginal, transdermal) progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) intrauterine device (IUD) intrauterine hormone-releasing system (IUS) bilateral tubal occlusion vasectomised partner sexual abstinence **Acceptable contraception is progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action