Clinical trial NCT04014829: Evaluation of Central Sensitization, Fear-Avoidance, and Pain-Pressure Threshold With Chronic Pain After Hysterectomy
Official title: 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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hysterectomy
Chronic Pain
Central Sensitisation
Anxiety Depression
Keywords: Hysterectomy
Chronic Pain
Fear-Avoidance
Central Sensitization
Pain-Pressure Threshold
Mechanical Temporal Summation
Heart rate variability
Lead sponsor: KK Women's and Children's Hospital
Sponsor class: OTHER_GOV
First posted: 2019-07-10
Enrollment: 436
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women scheduled for elective abdominal or laparoscopic hysterectomy at KK Women's and Children's Hospital, Singapore.

Brief 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.

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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.

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.

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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

Primary outcomes:
measure: Chronic Post-Hysterectomy Pain at 4 months
timeFrame: 4 months after hysterectomy
measure: Significant postoperative pain at 24 hours
timeFrame: 24 hours after hysterectomy
Secondary outcomes:
measure: Central Sensitization Inventory (CSI)
timeFrame: 2 months (upon recruitment until before surgery)
measure: Fear Avoidance Components Scale (FACS)
timeFrame: 2 months (upon recruitment until before surgery)
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 2 months (upon recruitment until before surgery)
measure: Pain Catastrophizing Scale (PCS)
timeFrame: 2 months (upon recruitment until before surgery)
measure: Quality of life via EQ-5D
timeFrame: 2 months (upon recruitment until before surgery)
measure: Mechanical Temporal Summation (MTS)
timeFrame: 2 months (upon recruitment until before surgery)
measure: Pain-Pressure Threshold (PPT)
timeFrame: 2 months (upon recruitment until before surgery)
measure: Chronic Post-Hysterectomy Pain at 6 months
timeFrame: 6 months after hysterectomy
measure: heart rate variability
timeFrame: Preoperative and 24 hours after hysterectomy
measure: Preoperative anxiety
timeFrame: Preoperative
measure: State-Trait Anxiety Inventory
timeFrame: 2 months (upon recruitment until before surgery)
measure: Beck's Depression Inventory
timeFrame: 2 months (upon recruitment until before surgery)
measure: Anticipated pain
timeFrame: Preoperative
measure: Anticipated analgesia requirement
timeFrame: Preoperative
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
Study officials:
affiliation: KK Women's and Children's Hospital
name: Farida Ithnin, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chapman CR, Vierck CJ. The Transition of Acute Postoperative Pain to Chronic Pain: An Integrative Overview of Research on Mechanisms. J Pain. 2017 Apr;18(4):359.e1-359.e38. doi: 10.1016/j.jpain.2016.11.004. Epub 2016 Nov 28.
citation: Han C, Ge Z, Jiang W, Zhao H, Ma T. Incidence and risk factors of chronic pain following hysterectomy among Southern Jiangsu Chinese Women. BMC Anesthesiol. 2017 Aug 11;17(1):103. doi: 10.1186/s12871-017-0394-3.
citation: Pinto PR, McIntyre T, Nogueira-Silva C, Almeida A, Araujo-Soares V. Risk factors for persistent postsurgical pain in women undergoing hysterectomy due to benign causes: a prospective predictive study. J Pain. 2012 Nov;13(11):1045-57. doi: 10.1016/j.jpain.2012.07.014. Epub 2012 Oct 12.
citation: Sng BL, Ching YY, Han NR, Ithnin FB, Sultana R, Assam PN, Sia ATH. Incidence and association factors for the development of chronic post-hysterectomy pain at 4- and 6-month follow-up: a prospective cohort study. J Pain Res. 2018 Mar 27;11:629-636. doi: 10.2147/JPR.S149102. eCollection 2018.
citation: Fingleton C, Smart K, Moloney N, Fullen BM, Doody C. Pain sensitization in people with knee osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2015 Jul;23(7):1043-56. doi: 10.1016/j.joca.2015.02.163. Epub 2015 Mar 5.
citation: Neblett R, Cohen H, Choi Y, Hartzell MM, Williams M, Mayer TG, Gatchel RJ. The Central Sensitization Inventory (CSI): establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample. J Pain. 2013 May;14(5):438-45. doi: 10.1016/j.jpain.2012.11.012. Epub 2013 Mar 13.
citation: Neblett R, Mayer TG, Hartzell MM, Williams MJ, Gatchel RJ. The Fear-avoidance Components Scale (FACS): Development and Psychometric Evaluation of a New Measure of Pain-related Fear Avoidance. Pain Pract. 2016 Apr;16(4):435-50. doi: 10.1111/papr.12333. Epub 2015 Jul 31.
citation: Brandsborg B, Dueholm M, Kehlet H, Jensen TS, Nikolajsen L. Mechanosensitivity before and after hysterectomy: a prospective study on the prediction of acute and chronic postoperative pain. Br J Anaesth. 2011 Dec;107(6):940-7. doi: 10.1093/bja/aer264. Epub 2011 Sep 2.