NCT04014829

Evaluation of Central Sensitization, Fear-Avoidance, and Pain-Pressure Threshold With Chronic Pain After Hysterectomy

Evaluation of Central Sensitization, Fear-Avoidance, and Pain-Pressure Threshold With Chronic Pain in Post-Hysterectomy Patients: A Collaborative Cohort Study (EPOCH - Enhancing Post-operative Outcomes in Chronic Pain After Hysterectomy)

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 436 (estimated)
• Sponsor: KK Women's and Children's Hospital · Other Government
• Sex: Female
• Age: 21 Years – 80 Years
• Healthy volunteers: Accepted

Summary

Phase 1 (started in July 2019): Central Sensitization Inventory (CSI), Fear-Avoidance Components Scale (FACS), pain-pressure threshold are factors associated with chronic post-hysterectomy pain (CPHP), but a complete understanding on the development of CPHP is lacking. The study aims to identify clinically-relevant factors for CPHP that can be reliably assessed preoperatively. === Phase 2 (anticipated start May 2022): In addition to above factors, the association between heart rate variability (HRV) parameters, anxiety level, anticipated pain, and anticipated analgesia requirement with significant postoperative pain and CPHP will be investigated.

Detailed description

Phase 1 (started in July 2019): Chronic post-surgical pain is persistent pain after a surgical procedure that lasts for at least 3 months with other causes of pain excluded. It is a major socioeconomic and healthcare burden, and has impact on quality of life, physical function, emotional wellbeing and healthcare costs. In Singapore, hysterectomy for benign indications incurs 32% risk of developing chronic post-hysterectomy pain (CPHP). CPHP can occur around the surgical site, lower abdominal or pelvic region. Based on the pathophysiology underlying chronic pain, the investigators hypothesize that central sensitization, pain fear-avoidance and low pain-pressure threshold are plausible risk factors for CPHP. However, none of these three risk categories has been evaluated in patients with CPHP. The investigators hypothesize that preoperatively abnormal central sensitization, pain fear-avoidance and decreased pain-pressure threshold are associated with increased risk of developing CPHP. The investigators will evaluate these risk factors preoperatively, and follow-up study participants at 4- and 6-months after hysterectomy, to assess the associations between these risk factors and CPHP. The investigators will perform a prospective study of 236 patients undergoing abdominal/laparoscopic hysterectomy for benign indications, recruited at KK Hospital, Singapore. Central Sensitization Inventory (CSI), Fear-Avoidance Components Scale (FACS), pain-pressure threshold and other known factors associated with CPHP will be assessed and recorded. Participants will be followed up at 4- and 6-months postoperatively to assess CPHP. Logistical regression analysis will be used to evaluate the associations between these factors and CPHP. Knowledge of risk factors for CPHP will guide future studies to identify high-risk patients for implementation of individualized targeted therapies to optimize surgical outcomes of this patient group, and to confirm the hypothetical pathophysiological processes of chronic post-surgical pain similarly applicable to CPHP. === Phase 2 (anticipated start May 2022): Recent evidence suggests that changes in heart rate variability (HRV) parameters, anxiety level, anticipated pain, and anticipated analgesia requirement may be associated with significant postoperative pain (numerical pain score \>3 out of 10). The associations between HRV, anxiety level, anticipated pain, and anticipated analgesia requirement with significant pain or CPHP after hysterectomy have yet been investigated. The investigators hypothesize that preoperative changes in HRV parameters, increased anxiety level, higher anticipated pain, and higher anticipated analgesia requirement are associated with increased risk of developing significant postoperative pain or CPHP. HRV, anxiety level, anticipated pain, and anticipated analgesia requirement will be assessed preoperatively, and follow-up study participants at 24 hours, 48 hours, 4- and 6-months after hysterectomy to assess their associations with significant postoperative pain and CPHP. The investigators will perform a prospective study of 200 patients undergoing abdominal/laparoscopic hysterectomy for benign indications, recruited at KK Hospital, Singapore. HRV, anxiety level, anticipated pain, and anticipated analgesia requirement will be assessed and recorded. Participants will be followed up at 24 hours, 48 hours, 4- and 6-months postoperatively to assess significant pain and CPHP. Logistical regression analysis will be used to evaluate the associations between these factors and significant pain or CPHP. Knowledge of risk factors for significant pain and CPHP will guide future studies to identify high-risk patients for implementation of individualized targeted therapies to optimize surgical outcomes of this patient group.

Conditions

• Hysterectomy
• Chronic Pain
• Central Sensitisation
• Anxiety Depression

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Pain-Pressure Threshold	Performed on bilateral trapezius muscles. Pressure will be applied at 90 degrees downward with an algometer, with the speed of pressure increase approximately 1kgf/s. Upon the sensation of pain, the patient will vocalize or raise her hand to terminate the test, and the highest reading will be recorded (up to maximum 6kgf). If two values are recorded within 0.2kgf of each other, the mean value will be recorded. If two values are greater than 0.2kgf of each other, a third test will be performed and the mean obtained.
DIAGNOSTIC_TEST	Mechanical Temporal Summation	Pinprick hyperalgesia will be evoked using a Von Frey filament, applied to the volar aspect of the dominant forearm. Participants will report using the numerical rating scale the intensity of pain from the first stimulus. Subsequently, ten repetitive stimuli one second apart will be applied with the same filament within an area of 1cm diameter of the same forearm. Subjects will report the rate the pain intensity of the tenth stimulus. The magnitude of MTS is calculated as the difference between the last to the first pain scores. The investigators will classify the participants according to "evoked MTS" if the last stimulus is rated higher than the first, or "no MTS" if the last stimulus is rated equal or lower than the first. The research team administering the test will follow a set script.
DIAGNOSTIC_TEST	Hospital Anxiety and Depression Scale	Standardized questionnaire to determine the level of anxiety and depression.
DIAGNOSTIC_TEST	Pain Catastrophizing Scale	Standardized questionnaire to determine the level of pain catastrophizing.
DIAGNOSTIC_TEST	Central Sensitization Inventory	Standardized questionnaire to determine the level of central sensitization.
DIAGNOSTIC_TEST	Fear-Avoidance Component Score	Standardized questionnaire to determine the level of fear and avoidance.
DIAGNOSTIC_TEST	EQ-5D	Standardized questionnaire to assess generic health-related quality of life.
DIAGNOSTIC_TEST	heart rate variability	Heart rate variability will be determined from the R-to-R intervals obtained from a 5-minute ECG recording.
DIAGNOSTIC_TEST	Anxiety, anticipated pain, anticipated analgesia	Preoperative anxiety (0 to 100), anticipated pain (0 to 100), and anticipated analgesia requirement (0 to 5).
DIAGNOSTIC_TEST	State-trait anxiety inventory	Standardized questionnaire to assess anxiety.
DIAGNOSTIC_TEST	Beck's Depression Inventory	Standardized questionnaire to assess depressive symptoms.

Timeline

• Start date: 2019-07-23
• Primary completion: 2025-12-01
• Completion: 2027-12-01
• First posted: 2019-07-10
• Last updated: 2024-11-26

Locations

1 site across 1 country: Singapore