Prediction and Characterization of Acute and Chronic Postoperative Pain

Study Overview
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Brief Summary
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Despite enormous progress insufficient postoperative pain management remains a frequent problem in the early postoperative phase after surgery. Furthermore, the pain that persists after healing of the surgical wound is a large, but often unrecognized, clinical problem and it is estimated that 5-10% of those undergoing surgery will develop severe persistent pain leading to chronic disability and psychosocial distress. Conditioned Pain Modulation (CPM), also known as the phenomenon pain-inhibits-pain, is a reduction in pain somewhere on the body in response to the application of a second painful stimulus outside the painful area. In recent years, the CPM has been identified as a psycho-physical measure with clinical relevance in characterizing the individual's ability to modulate pain and consequently the individual's disposition to acquire painful conditions. The purpose of this study is primarily to assess the relationship between CPM efficacy and clinical postoperative pain (postoperative pain intensity, use of analgesics, the intensity of secondary hyperalgesia and allodynia, and the incidence of persistent postoperative pain) associated with minimally invasive repair of pectus excavatum. In addition, the study aims at identifying other patient- and/or surgery-related factors affecting the course of postoperative pain. Hypothesis: - The greater the positive difference between the experimental pressure pain threshold (kPa) measured before and after application of a second painful stimulus (Cold Pressor Test), the lower the risk of developing persistent postoperative pain. Secondary hypotheses The greater the positive difference between the experimental pressure pain threshold (kPa) measured before and after application of a different experimental painful stimulus (Cold Pressor Test) lower the pain intensity in the early postoperative period. The greater the positive difference between the experimental pressure pain threshold (kPa) measured before and after application of a different experimental painful stimulus (Cold Pressor Test), the shorter duration of early postoperative pain. The greater the positive difference between the experimental pressure pain threshold (kPa) measured before and after application of a different experimental painful stimulus (Cold Pressor Test), the lower the usage of epidural analgesia (mg / ml). The larger the positive difference between the experimental pressure pain threshold (kPa) measured before and after application of a different experimental painful stimulus (Cold Pressor Test) the lower consumption of oral analgesics (mg / day). Severe acute pain in the early postoperative period (postoperative days 0-3) is positively associated with the development of persistent postoperative pain (6 months postoperatively). Presence of preoperative pain and / or high postoperative use of analgesics and / or high pain intensity during the first 6-8 weeks postoperatively predicts pain 6 months postoperatively. The higher pain intensity and discomfort associated with brush-evoked allodynia and / or pinprick (Von Frey) secondary hyperalgesia the greater the risk for developing persistent postoperative pain (6 months postoperatively). High levels of preoperative catastrophizing (assessed on the day of admission) is related to the severity of acute pain (rated third postoperative day) and chronic pain (assessed 6 months postoperatively), even if controlled for depression and anxiety. The degree of preoperative positive and negative emotions (as assessed on the day of admission) is related to the degree of acute pain (rated third postoperative day) and chronic pain (assessed 6 months postoperatively) so that negative emotions are associated with high levels of pain, while positive feelings are related to low levels of pain. The study population does not differ significantly from the normal population in terms of personality traits (emotional reactions, extraversion, openness to experience, friendliness, conscientiousness). The study population does not experience a significant change in personality traits during the first 6 months after surgery. The quality of life and self-esteem is lower among patients who develop persistent postoperative pain compared with pain patients. Quality of life and self-esteem improve as a result of minimally invasive repair of pectus excavatum.

Official Title
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Prediction and Characterization of Acute and Chronic Postoperative Pain - a Longitudinal Observational Study of the Relationship Between Experimental Pain Modulation and Clinical Postoperative Pain in Patients Undergoing Minimally Invasive Repair of Pectus Excavatum

Conditions
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Pain, Pain, Postoperative, Funnel Chest

Intervention / Treatment
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* Other: Conditioned pain modulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing minimally invasive repair of pectus excavatum Age > 15 years old Exclusion Criteria: Previous thoracic surgery interventions Disorders affecting the central or peripheral nervous system Chronic pain (pain intensity assessed by numerical rating scale > 3) Inability to speak and understand Danish (instructions, questionnaires) Inability to understand and participate in experimental pain modulation Psychiatric disorders (ICD-10) A history of frostbite in the non-dominant upper limb Sores or cuts on non-dominant upper limb Cardiovascular disease A history of fainting and/or seizures Fracture in non-dominant upper limb Reynaud's phenomenon

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with pectus excavatum<br> | Other: Conditioned pain modulation<br>* When evaluating conditioned pain modulation, pressure pain threshold in the musculus quadriceps femoris act as test stimulus and 2 minutes cold pressor test (stirred ice and water) acts as the conditioning stimulus. The difference between pain thresholds before and after the cold pressor test is defined as the effect of CPM.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistent postoperative pain | Pain that develops and persists after minimally invasive repair of pectus excavatum. Other causes of pain (e.g. infection) and preoperatively defined painful conditions are are excluded. | 6 months postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity at rest | Pain intensity is measured by means of an 11-point numerical rating scale with the verbal anchors No pain and Worst pain imaginable | Daily for up to 42 days postoperatively, at 6 months follow-up | 
| Pain intensity when active | Pain intensity is measured by means of an 11-point numerical rating scale with the verbal anchors No pain and Worst pain imaginable | Daily for up to 42 days postoperatively, at 6 months follow-up | 
| Pain unpleasantness/discomfort at rest | Pain unpleasantness/discomfort is measured by means of an 11-point numerical rating scale with the verbal anchors No unpleasantness/discomfort and Worst unpleasantness/discomfort imaginable | Daily for up to 42 days postoperatively, at 6 months follow-up | 
| Pain unpleasantness/discomfort when active | Pain unpleasantness/discomfort is measured by means of an 11-point numerical rating scale with the verbal anchors No unpleasantness/discomfort and Worst unpleasantness/discomfort imaginable | Daily for up to 42 days postoperatively, at 6 months follow-up | 
| Pain location | Painful areas are marked on a figure illustrating a human torso (both front and back are shown). The figure has predefined squares in order to standardize report. | Daily for up to 42 days postoperatively, at 6 months follow-up | 
| Postoperative usage of analgesics | Usage of analgesics is divided into non-opioid and opioid analgesics and into prescribed and as needed usage. | Daily for up to 42 days postoperatively, at 6 months follow-up | 
| Postoperative usage epidural analgesia | Usage of epidural analgesia is measured as both total and bolus infusion of epidural analgesics i millilitres (Ml) | Within 4 days postoperatively | 
| Intensity of brush-evoked pain (mechanical allodynia) | Any pain evoked by brush on the thorax (mechanical allodynia) is rated on 11-point numerical rating scale with the verbal anchors No pain and Worst pain imaginable | At 6 weeks follow-up | 
| Intensity of brush-evoked discomfort (mechanical allodynia) | Any discomfort evoked by brush on the thorax (mechanical allodynia) is rated on 11-point numerical rating scale with the verbal anchors No discomfort and Worst discomfort imaginable | At 6 weeks follow-up | 
| Dysaesthesia | Presence of dysaesthesia when stroking the skin on the thorax with a brush | At 6 weeks follow-up | 
| Intensity of pinprick-evoked pain (mechanical dynamical hyperalgesia) | Any pain evoked by pinprick (Von Frey) on the thorax (mechanical dynamical hyperalgesia) is rated on 11-point numerical rating scale with the verbal anchors No pain and Worst pain imaginable | At 6 weeks follow-up | 
| Hypoalgesia (skin) | Presence of hypoalgesia on the thorax is defined as a reduced response to pinprick (Von Frey) | At 6 weeks follow-up | 
| Peri-incisional secondary hyperalgesia | Negative difference between pressure pain thresholds (skinfold pinch) measured before surgery and at 6 weeks follow-up. Meassurements are made with a handheld pressure algometer 5 cm distal to the papilla | At 6 weeks follow-up | 
| Generalized secondary hyperalgesia | Negative difference between pressure pain thresholds (musculus quadriceps femoris) measured before surgery and at 6 weeks follow-up. Meassurements are made with a handheld pressure algometer in the quadriceps 10 cm above to the patella | At 6 weeks follow-up | 
| Personality | Response to Neuroticism, extraversion, openness, personality inventory - revised (NEO-PI-R) at 6 months follow-up compared to baseline | At 6 months follow-up | 
| Pain Catastrophizing | Responses to the Pain Catastrophizing Scale (PCS) compared to baseline | At baseline, following coldpressor test, at 3 days postoperatively, at 6 months follow-up | 
| Anxiety | Responses to the State-Trait Anxiety Inventory (STAI) compared to baseline | At baseline, following coldpressor test, at 3 days postoperatively, at 6 months follow-up | 
| Depression | Responses to the Beck's depression Inventory - second edition (BPI-II) compared to baseline | At baseline, at 3 days postoperatively, at 6 months follow-up | 
| Emotions | Responses to the Positive and Negative Affective Scale (PANAS) compared to baseline | At baseline, at 3 days postoperatively, at 6 months follow-up | 
| Health-related Quality of life | Responses to the Short Form Health Survey (SF-36) compared to baseline | At baseline, at 6 months follow-up | 
| Self-esteem | Responses to the Rosenberg Self-esteem Scale (SES) compared to baseline | At baseline, at 6 months follow-up | 
| Qualitative dimension of pain | Responses to the McGill Pain Questionnaire - short form (SF-MPQ) compared to baseline | At baseline, following coldpressor test, at 3 days postoperatively, at 6 weeks follow-up, at 6 months follow-up | 
| Pain interference with daily life | Responses to the Brief Pain Inventory - short form (SF-BPI) compared to baseline | At baseline, at 6 weeks follow-up, at 6 months follow-up | 
| Course of pain | Course of pain is defined as 1.) constant pain with few fluctuations, 2.) constant pain with breakthrough pain, 3.) Breakthrough pain without pain in between, 4.) Breakthrough pain with pain in between. | At 6 weeks follow-up, at 6 months follow-up |