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

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.

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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.

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.

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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.

Eligibility Criteria:
Inclusion Criteria:

* Age 21 to 80 years old
* American Society of Anesthesiologists Physical Scale (ASA) I to III
* Benign gynaecological indications for hysterectomy
* Elective abdominal or laparoscopic hysterectomy

Exclusion Criteria:

* Vaginal hysterectomy
* Uterine prolapse, endometriosis, malignant disease, or pelvic pain as main indication for surgery
* History of drug dependence or recreational drug use
* History of chronic pain syndrome
* Current chronic daily treatment with corticosteroids, excluding inhaled steroids
* Allergy to study drugs
* Major heart surgery
* Heart transplant
* Pacemaker inserted
* Baseline non-sinus cardiac rhythm