The purpose of this study is to define the role of preemptive systemic analgesia in combination with regional anesthetic techniques on postoperative pain following upper limb surgery in different subgroups of patients with different psychosocial and psychophysical characteristics.

After being informed about the study and potential risks, patients will be given written informed consent. The study will include patients between the ages of 18 and 65, rated 1 or 2 by the American Society of Anesthesiologists (ASA) classification scheduled for distal radius surgery.

We will exclude patients with a known allergy to or adverse reaction to a local anesthetic, opioid, paracetamol or non-steroidal anti-inflammatory drugs, patients with a known opioid dependence, injection site infection, chronic pain, renal disease, known neuropathy, liver disease, with psychiatric disorders and diabetics.

The study will be randomized, prospective and double-blind. We will study the effect of preemptive dose of paracetamol and ibuprofen and pregabalin on postoperative pain after distal radius surgery in patients with different psychosocial and psychophysical characteristics. Patients will be admitted to the ward the day before surgery. At that time, we will explain to them the course of the research and offer them participation. For those with a written consent we will perform preoperative quantitative sensory tests on the same day and give them pain questionnaires.

We will determine conditional pain modulation by first applying a mechanical test stimulus of increasing intensity with an algometer to the skin of the volar side of the forearm and the skin in the middle of the front of the thigh contralateral to the injury until the patient experiences pain on the visual analog scale (VAS) 4/10. At that point the patients will press the patient operated button on the algometer and the stimulus will be stopped with the measurement stored. We will then repeat the same test together with a conditional stimulus - immersion of the ipsilateral lower extremity in cold water at 2 degrees Celsius. Conditional pain modulation will be calculated by subtracting the intensity of the independent primary stimulus from the intensity of the primary stimulus together with a concomitant conditioned stimulus. The end result will be the average of the values obtained on the skin of the volar side of the forearm and the skin in the middle of the front of the thigh.

On the same day the patients will also complete a Pain Catastrophising Scale (PCS) Questionnaire and a Brief Pain Inventory (BPI). They will also receive a short questionnaire to assess the pain and quality of sleep on the first night after surgery, which they will complete together with an anesthesiologist the morning after surgery.

On the day of surgery, patients will be divided into 3 groups:

The first group will receive pregabalin 150 mg per os 1 hour before arrival in the operating room and two intravenous doses of 100 ml of saline within 30 minutes before the surgical incision.

The second group will receive a placebo capsule per os 1 hour before arrival in the operating room and a preemptive intravenous dose of paracetamol 1 g and ibuprofen 400 mg within 30 minutes before the surgical incision.

The third group will receive a placebo capsule per os 1 hour before arrival in the operating room and two intravenous doses of 100 ml of saline within 30 minutes before the surgical incision.

All three groups will then receive an axillary block under ultrasound control by an experienced anesthesiologist. They may receive midazolam and/or fentanyl/sufentanil for anxiolysis and analgesia during the blockade. The surgery will be performed with of without sedation with propofol, titrated to desired effect. In the event of a failed block, patients will be placed under general anesthesia and excluded from the study. For postoperative nausea and vomiting they will not receive dexamethasone.

Postoperative analgesia:

For the postoperative analgesia, patients will receive a PCA (patient controlled analgesia) pump with Piritramide 45 mg diluted to 90 ml of saline. The PCA pump will have no continuous flow. The PCA boluses will be 3 mg every 20 minutes, with a 2 hour limit of 9 mg and a 6 hour limit of 15 mg. The PCA pump will be connected to the patients for at least 24 hours.

If necessary, the ward nurse will administer an additional intravenous dose of Piritramide 3 mg every 4 hours in case of insufficient analgesia (pain on VAS > 3/10). Patients will additionally receive intravenous Paracetamol 1 g every 6 h and intravenous Ibuprofen 400 mg every 8 hours.

For 24 hours after surgery we will record pain experienced by the patients, based on the VAS. Opioid consumption will be recorded by the PCA pump, any additional boluses by the nurses will be added to the total consumption. The first day after surgery, 14 days after surgery and 3 months after surgery the patients will again complete a BPI questionnaire. We will also document the interval between the injury and surgery, time of surgery, AO Distal Radius Fracture Classification, surgical approach and type of osteosynthesis.

We will study the impact of psychosocial, psychophysical and preemptive systemic analgesia on acute and chronic postoperative pain in distal radius surgery. We will examine whether patients with different psychosocial and psychophysical characteristics benefit differently from different regimens of preemptive systemic analgesia.

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) classification score 1 and 2
• Patients with a distal radius fracture, scheduled for surgery

Exclusion Criteria:

• Allergy to a local anesthetic, opioid, paracetamol or a non-steroidal antirheumatic drug
• Opioid addiction
• Infection at the injection site
• Chronic pain syndromes
• Neuropathies
• Liver cirrhosis
• Chronic kidney disease stage 3 or higher
• Diabetes
• Psychiatric illness

We will include all IPD that underlie results in a publication

Immediately following publication. No end date.

Anyone who wishes to access the data.

Participants will receive either the actual drug or placebo. A separate investigator will be in charge of preparing the capsules and intravenous solutions that patients will receive before surgery in a way that it will not be possible to determine whether it is an actual drug or a placebo. That investigator will also write in which group the patient is on a piece of paper and insert it in the patient's inventory for safety purposes. The person that will measure the conditioned pain modulation and complete the pain questionnaires with patients will be a separate investigator. The anesthesiologist performing the axillary block will also be blinded, because the drugs/placebo will be prepared by a separate investigator. We will code the group to which the patients are allocated, so that the Outcomes Assessor will also be blinded.