HysterectomyEPOCHNCT04014829
Evaluation of Central Sensitization, Fear-Avoidance, and Pain-Pressure Threshold With Chronic Pain After Hysterectomy
An observational study of Hysterectomy and Chronic Pain, run by KK Women's and Children's Hospital at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 80 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Hysterectomy, Chronic Pain, Central Sensitisation
- What is being tested?
- Pain-Pressure Threshold, Mechanical Temporal Summation and Hospital Anxiety and Depression Scale
- How many people
- 436 participants
- Where
- 1 siteSingapore
- Study dates
- 23 Jul 2019to Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Women scheduled for elective abdominal or laparoscopic hysterectomy at KK Women's and Children's Hospital, Singapore.
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- Major heart surgery
- Heart transplant
- Pacemaker inserted
- Baseline non-sinus cardiac rhythm
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Singapore1 site, 1 recruiting
- Recruiting
KK Women's and Children's Hospital
Singapore, 229899
Hon Sen Tan, MD, paul.tan.hs@singhealth.com.sg
About this study
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)
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.
Read the 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
- Being tested
- Pain-Pressure Threshold, Mechanical Temporal Summation, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, Central Sensitization Inventory
- Keywords
- Hysterectomy, Chronic Pain, Fear-Avoidance, Central Sensitization, Pain-Pressure Threshold, Mechanical Temporal Summation, Heart rate variability
- Medical subject headings
- Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pain-Pressure ThresholdDiagnostic test
Also called PPT
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.
Mechanical Temporal SummationDiagnostic test
Also called MTS
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.
Hospital Anxiety and Depression ScaleDiagnostic test
Also called HADS
Standardized questionnaire to determine the level of anxiety and depression.
Pain Catastrophizing ScaleDiagnostic test
Also called PCS
Standardized questionnaire to determine the level of pain catastrophizing.
Central Sensitization InventoryDiagnostic test
Also called CSI
Standardized questionnaire to determine the level of central sensitization.
Fear-Avoidance Component ScoreDiagnostic test
Also called FACS
Standardized questionnaire to determine the level of fear and avoidance.
EQ-5DDiagnostic test
Standardized questionnaire to assess generic health-related quality of life.
heart rate variabilityDiagnostic test
Also called HRV
Heart rate variability will be determined from the R-to-R intervals obtained from a 5-minute ECG recording.
Anxiety, anticipated pain, anticipated analgesiaDiagnostic test
Preoperative anxiety (0 to 100), anticipated pain (0 to 100), and anticipated analgesia requirement (0 to 5).
State-trait anxiety inventoryDiagnostic test
Also called STAI
Standardized questionnaire to assess anxiety.
Beck's Depression InventoryDiagnostic test
Also called BDI
Standardized questionnaire to assess depressive symptoms.
| Study group | Role | What they receive |
|---|---|---|
| Control group for CPHP | Preoperative assessment with questionnaires, Mechanical Temporal Summation, Pain-Pressure Threshold, and heart rate variability. All patients will undergo elective abdominal or laparoscopic hysterectomy. Patients will be assigned to this group if no significant pain is noted during the follow up evaluations at 4 and 6 months. Receives: Diagnostic Test: Pain-Pressure Threshold; Diagnostic Test: Mechanical Temporal Summation; Diagnostic Test: Hospital Anxiety and Depression Scale; Diagnostic Test: Pain Catastrophizing Scale; Diagnostic Test: Central Sensitization Inventory; Diagnostic Test: Fear-Avoidance Component Score; Diagnostic Test: EQ-5D; Diagnostic Test: heart rate variability; Diagnostic Test: Anxiety, anticipated pain, anticipated analgesia; Diagnostic Test: State-trait anxiety inventory; Diagnostic Test: Beck's Depression Inventory | |
| Chronic Post-Hysterectomy Pain (CPHP) | Preoperative assessment with questionnaires, Mechanical Temporal Summation, Pain-Pressure Threshold, and heart rate variability. All patients will undergo elective abdominal or laparoscopic hysterectomy. Patients will be assigned to this group if significant pain is noted during the follow up evaluations at 4 and 6 months. Receives: Diagnostic Test: Pain-Pressure Threshold; Diagnostic Test: Mechanical Temporal Summation; Diagnostic Test: Hospital Anxiety and Depression Scale; Diagnostic Test: Pain Catastrophizing Scale; Diagnostic Test: Central Sensitization Inventory; Diagnostic Test: Fear-Avoidance Component Score; Diagnostic Test: EQ-5D; Diagnostic Test: heart rate variability; Diagnostic Test: Anxiety, anticipated pain, anticipated analgesia; Diagnostic Test: State-trait anxiety inventory; Diagnostic Test: Beck's Depression Inventory | |
| Control group for significant postoperative pain | Preoperative assessment with questionnaires, Mechanical Temporal Summation, Pain-Pressure Threshold, and heart rate variability. All patients will undergo elective abdominal or laparoscopic hysterectomy. Patients will be assigned to this group if no significant pain is noted during the follow up evaluations at 24 and 48 hours. Receives: Diagnostic Test: Pain-Pressure Threshold; Diagnostic Test: Mechanical Temporal Summation; Diagnostic Test: Hospital Anxiety and Depression Scale; Diagnostic Test: Pain Catastrophizing Scale; Diagnostic Test: Central Sensitization Inventory; Diagnostic Test: Fear-Avoidance Component Score; Diagnostic Test: EQ-5D; Diagnostic Test: heart rate variability; Diagnostic Test: Anxiety, anticipated pain, anticipated analgesia; Diagnostic Test: State-trait anxiety inventory; Diagnostic Test: Beck's Depression Inventory | |
| Significant postoperative pain | Preoperative assessment with questionnaires, Mechanical Temporal Summation, Pain-Pressure Threshold, and heart rate variability. All patients will undergo elective abdominal or laparoscopic hysterectomy. Patients will be assigned to this group if significant pain is noted during the follow up evaluations at 24 and 48 hours. Receives: Diagnostic Test: Pain-Pressure Threshold; Diagnostic Test: Mechanical Temporal Summation; Diagnostic Test: Hospital Anxiety and Depression Scale; Diagnostic Test: Pain Catastrophizing Scale; Diagnostic Test: Central Sensitization Inventory; Diagnostic Test: Fear-Avoidance Component Score; Diagnostic Test: EQ-5D; Diagnostic Test: heart rate variability; Diagnostic Test: Anxiety, anticipated pain, anticipated analgesia; Diagnostic Test: State-trait anxiety inventory; Diagnostic Test: Beck's Depression Inventory |
What is being measured
The primary outcome is the main question the study is designed to answer.
Chronic Post-Hysterectomy Pain at 4 months
The primary outcome measure is the development of chronic post-hysterectomy pain, which is defined as pain that lasts for at least 3 months around the surgical site, lower abdominal, or pelvic region. This will be determined by phone or online assessment at 4 months after surgery, based on the protocol used by Brandsborg et al and the investigators' previous study.
Measured: 4 months after hysterectomy
Significant postoperative pain at 24 hours
Numerical pain score (0: no pain; 100: worst pain imaginable) will be assessed at 24 hours after hysterectomy with patient moving from supine to sitting position.
Measured: 24 hours after hysterectomy
Secondary outcomes (14)
Central Sensitization Inventory (CSI)
Assessment via the validated Central Sensitization Inventory (CSI) questionnaire prior to hysterectomy. Central sensitization is defined as an increased responsiveness of nociceptive neurons in the central nervous system to normal or sub-threshold afferent stimuli. The CSI a 25-item questionnaire, with each item rated 0 to 4. A higher value indicates greater central sensitization, and a threshold score of 40 was shown to be associated with increased risk of chronic pain.
Measured: 2 months (upon recruitment until before surgery)
Fear Avoidance Components Scale (FACS)
Assessment via the validated Fear Avoidance Components Scale (FACS) questionnaire prior to hysterectomy. Fear-avoidance is defined as the negative emotional perception of pain as terrorizing, which can generate catastrophic thoughts and vigilance. Pain fear-avoidance behavior can be assessed with the FACS, a 20-item questionnaire, with each item rated 0 to 5.
Measured: 2 months (upon recruitment until before surgery)
Hospital Anxiety and Depression Scale (HADS)
Assessment via the validated Hospital Anxiety and Depression Scale (HADS) questionnaire prior to hysterectomy. Anxiety and depression are known risk factors associated with CPHP. HADS is a combination test for both anxiety and depression, is a 14-item questionnaire, with each item rated 0 to 3. HADS > 8 has been associated specifically with increased CPHP.
Measured: 2 months (upon recruitment until before surgery)
Pain Catastrophizing Scale (PCS)
Assessment via the validated Pain Catastrophizing Scale (PCS) questionnaire prior to hysterectomy. Pain catastrophizing refers to the negative thought processes patients have when they are exposed to pain or painful experiences. The PCS is a 13-item scale, with each item rated on a 5-point scale: 0 (Not at all) to 4 (all the time). It is broken into three subscales being magnification (0-12), rumination (0-16), and helplessness (0-24). A higher value in each subscale indicates a higher tendency to that subscale (worse outcome).
Measured: 2 months (upon recruitment until before surgery)
Quality of life via EQ-5D
Assessment via the validated EQ-5D questionnaire prior to hysterectomy. Lower preoperative quality of life has been associated with CPHP. EQ-5D is a validated questionnaire to assess generic health-related quality of life, consisting of two components: health state description and evaluation.
The description component measures health status via five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, with each dimension rated according to severity using a three-level scale.
The evaluation component assesses overall health status using the visual analogue scale (EQ-VAS).
Measured: 2 months (upon recruitment until before surgery)
Mechanical Temporal Summation (MTS)
Assessment via Mechanical Temporal Summation before hysterectomy. A 180 gram von Frey filament is applied on the subject's forearm. Patient will then be asked to rate the pinprick pain score on a verbal rating scale, 0-100. Following this, 10 consecutive touches at random locations are applied with a 1 second interstimulus interval and within a 1 cm diameter circle. The patient will then be asked to rate the 10th pain score (0-100). The Mechanical Temporal Summation Score is obtained by the difference between the 11th pain score and the 1st pain score. If the score is greater than zero, the patient is implied to have presence of Mechanical Temporal Summation.
Measured: 2 months (upon recruitment until before surgery)
Pain-Pressure Threshold (PPT)
Assessment of Pain-pressure threshold (PPT) prior to hysterectomy. PPT is measured via an algometer in both groups. Pressure is applied 90 degree straight down force on the subject's right/left centre of the trapezius muscle using an algometer, with a speed of pressure ~ 1kgf/s. The above procedure is then repeated 3 times at each site (left/right) which is indicated on the pressure mark with each time having the reading recorded. When patient shows no response ≥ 6kgf, the threshold is recorded as 6kgf. The patient upon feeling pain will say stop or raise the hand to terminate the test. The mean value is obtained by averaging the readings and will then be recorded as the threshold estimate.
Measured: 2 months (upon recruitment until before surgery)
Chronic Post-Hysterectomy Pain at 6 months
The primary outcome measure is the development of chronic post-hysterectomy pain, which is defined as pain that lasts for at least 3 months around the surgical site, lower abdominal, or pelvic region. This will be determined by phone or online assessment at 6 months after surgery, based on the protocol used by Brandsborg et al and the investigators' previous study.
Measured: 6 months after hysterectomy
heart rate variability
Heart rate variability will be determined from the R-to-R intervals obtained from a 5 minute ECG recording with the patient supine.
Measured: Preoperative and 24 hours after hysterectomy
Preoperative anxiety
Patients will be asked to rate, using a 0-100 mm visual analog scale (VAS), their surgical anxiety level ("On a scale of 0-100, with 0 being not anxious at all through 100 being extremely anxious, how anxious are you about your upcoming surgery?")
Measured: Preoperative
State-Trait Anxiety Inventory
Assessment via State-Trait Anxiety Inventory questionnaire prior to hysterectomy, a standardized assessment of anxiety. This is a validated 40-item questionnaire, each item scored using a categorical scale from 1-4, with total score from 40 to 160.
Measured: 2 months (upon recruitment until before surgery)
Beck's Depression Inventory
Assessment via Beck's Depression Inventory questionnaire prior to hysterectomy, a standardized assessment of depressive symptoms.This is a validated 21-item questionnaire, each item scored using a categorical scale from 0-3, with total score from 0 to 63.
Measured: 2 months (upon recruitment until before surgery)
Anticipated pain
Patients will be asked to rate, using a 0-100 mm visual analog scale (VAS), their anticipated pain ("On a scale of 0-100, with 0 being no pain at all and 100 being pain as bad as you can imagine, how much pain do you anticipate experiencing after your upcoming surgery?")
Measured: Preoperative
Anticipated analgesia requirement
Patients will be asked to rate, using a categorical scale, their anticipated pain medication need ("On a scale of 0-5, with 0 being none at all, 1 being much less than average, 2 being less than average, 3 being average, 4 being more than average, and 5 being much more than average, how much pain medication do you anticipate needing after your upcoming surgery?")
Measured: Preoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2019
- Study start23 Jul 2019
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for HysterectomyStudies of the same condition, open and under way.
- More trials run by KK Women's and Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 436 participants (estimated)
Sponsor and investigators
- Lead sponsor
- KK Women's and Children's Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Sng Ban Leong, KK Women's and Children's Hospital
- Investigators
- Farida Ithnin, MBBS, Principal investigator, KK Women's and Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04014829
- Sponsor's protocol ID
- EPOCH
- Acronym
- EPOCH
- Status last verified
- Aug 2026
- First submitted
- 5 Jul 2019
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27908839Han 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.
PubMed 28800726Pinto 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.
PubMed 23063345Sng 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.
PubMed 29628772Fingleton 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.
PubMed 25749012Neblett 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.
PubMed 23490634Neblett 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.
PubMed 26228238Brandsborg 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.
PubMed 21890662
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04014829
- Acronym / sponsor ID
- EPOCH / EPOCH
- 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
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 436 participants (estimated)
- Lead sponsor
- KK Women's and Children's HospitalOther government
- Study start
- 23 Jul 2019 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 10 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Control group for CPHP | – | Diagnostic Test: Pain-Pressure Threshold, Diagnostic Test: Mechanical Temporal Summation, Diagnostic Test: Hospital Anxiety and Depression Scale, Diagnostic Test: Pain Catastrophizing Scale, Diagnostic Test: Central Sensitization Inventory, Diagnostic Test: Fear-Avoidance Component Score, Diagnostic Test: EQ-5D, Diagnostic Test: heart rate variability, Diagnostic Test: Anxiety, anticipated pain, anticipated analgesia, Diagnostic Test: State-trait anxiety inventory, Diagnostic Test: Beck's Depression InventoryPreoperative assessment with questionnaires, Mechanical Temporal Summation, Pain-Pressure Threshold, and heart rate variability. All patients will undergo elective abdominal or laparoscopic hysterectomy. Patients will be assigned to this group if no significant pain is noted during the follow up evaluations at 4 and 6 months. |
| Chronic Post-Hysterectomy Pain (CPHP) | – | Diagnostic Test: Pain-Pressure Threshold, Diagnostic Test: Mechanical Temporal Summation, Diagnostic Test: Hospital Anxiety and Depression Scale, Diagnostic Test: Pain Catastrophizing Scale, Diagnostic Test: Central Sensitization Inventory, Diagnostic Test: Fear-Avoidance Component Score, Diagnostic Test: EQ-5D, Diagnostic Test: heart rate variability, Diagnostic Test: Anxiety, anticipated pain, anticipated analgesia, Diagnostic Test: State-trait anxiety inventory, Diagnostic Test: Beck's Depression InventoryPreoperative assessment with questionnaires, Mechanical Temporal Summation, Pain-Pressure Threshold, and heart rate variability. All patients will undergo elective abdominal or laparoscopic hysterectomy. Patients will be assigned to this group if significant pain is noted during the follow up evaluations at 4 and 6 months. |
| Control group for significant postoperative pain | – | Diagnostic Test: Pain-Pressure Threshold, Diagnostic Test: Mechanical Temporal Summation, Diagnostic Test: Hospital Anxiety and Depression Scale, Diagnostic Test: Pain Catastrophizing Scale, Diagnostic Test: Central Sensitization Inventory, Diagnostic Test: Fear-Avoidance Component Score, Diagnostic Test: EQ-5D, Diagnostic Test: heart rate variability, Diagnostic Test: Anxiety, anticipated pain, anticipated analgesia, Diagnostic Test: State-trait anxiety inventory, Diagnostic Test: Beck's Depression InventoryPreoperative assessment with questionnaires, Mechanical Temporal Summation, Pain-Pressure Threshold, and heart rate variability. All patients will undergo elective abdominal or laparoscopic hysterectomy. Patients will be assigned to this group if no significant pain is noted during the follow up evaluations at 24 and 48 hours. |
| Significant postoperative pain | – | Diagnostic Test: Pain-Pressure Threshold, Diagnostic Test: Mechanical Temporal Summation, Diagnostic Test: Hospital Anxiety and Depression Scale, Diagnostic Test: Pain Catastrophizing Scale, Diagnostic Test: Central Sensitization Inventory, Diagnostic Test: Fear-Avoidance Component Score, Diagnostic Test: EQ-5D, Diagnostic Test: heart rate variability, Diagnostic Test: Anxiety, anticipated pain, anticipated analgesia, Diagnostic Test: State-trait anxiety inventory, Diagnostic Test: Beck's Depression InventoryPreoperative assessment with questionnaires, Mechanical Temporal Summation, Pain-Pressure Threshold, and heart rate variability. All patients will undergo elective abdominal or laparoscopic hysterectomy. Patients will be assigned to this group if significant pain is noted during the follow up evaluations at 24 and 48 hours. |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Women scheduled for elective abdominal or laparoscopic hysterectomy at KK Women's and Children's Hospital, Singapore.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pain-Pressure ThresholdAlso: PPTPerformed 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 | Chronic Post-Hysterectomy Pain (CPHP), Control group for CPHP, Control group for significant postoperative pain, Significant postoperative pain |
| Mechanical Temporal SummationAlso: MTSPinprick 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 | Chronic Post-Hysterectomy Pain (CPHP), Control group for CPHP, Control group for significant postoperative pain, Significant postoperative pain |
| Hospital Anxiety and Depression ScaleAlso: HADSStandardized questionnaire to determine the level of anxiety and depression. | Diagnostic test | Chronic Post-Hysterectomy Pain (CPHP), Control group for CPHP, Control group for significant postoperative pain, Significant postoperative pain |
| Pain Catastrophizing ScaleAlso: PCSStandardized questionnaire to determine the level of pain catastrophizing. | Diagnostic test | Chronic Post-Hysterectomy Pain (CPHP), Control group for CPHP, Control group for significant postoperative pain, Significant postoperative pain |
| Central Sensitization InventoryAlso: CSIStandardized questionnaire to determine the level of central sensitization. | Diagnostic test | Chronic Post-Hysterectomy Pain (CPHP), Control group for CPHP, Control group for significant postoperative pain, Significant postoperative pain |
| Fear-Avoidance Component ScoreAlso: FACSStandardized questionnaire to determine the level of fear and avoidance. | Diagnostic test | Chronic Post-Hysterectomy Pain (CPHP), Control group for CPHP, Control group for significant postoperative pain, Significant postoperative pain |
| EQ-5DStandardized questionnaire to assess generic health-related quality of life. | Diagnostic test | Chronic Post-Hysterectomy Pain (CPHP), Control group for CPHP, Control group for significant postoperative pain, Significant postoperative pain |
| heart rate variabilityAlso: HRVHeart rate variability will be determined from the R-to-R intervals obtained from a 5-minute ECG recording. | Diagnostic test | Chronic Post-Hysterectomy Pain (CPHP), Control group for CPHP, Control group for significant postoperative pain, Significant postoperative pain |
| Anxiety, anticipated pain, anticipated analgesiaPreoperative anxiety (0 to 100), anticipated pain (0 to 100), and anticipated analgesia requirement (0 to 5). | Diagnostic test | Chronic Post-Hysterectomy Pain (CPHP), Control group for CPHP, Control group for significant postoperative pain, Significant postoperative pain |
| State-trait anxiety inventoryAlso: STAIStandardized questionnaire to assess anxiety. | Diagnostic test | Chronic Post-Hysterectomy Pain (CPHP), Control group for CPHP, Control group for significant postoperative pain, Significant postoperative pain |
| Beck's Depression InventoryAlso: BDIStandardized questionnaire to assess depressive symptoms. | Diagnostic test | Chronic Post-Hysterectomy Pain (CPHP), Control group for CPHP, Control group for significant postoperative pain, Significant postoperative pain |
Primary outcome
Chronic Post-Hysterectomy Pain at 4 months
Time frame: 4 months after hysterectomy
The primary outcome measure is the development of chronic post-hysterectomy pain, which is defined as pain that lasts for at least 3 months around the surgical site, lower abdominal, or pelvic region. This will be determined by phone or online assessment at 4 months after surgery, based on the protocol used by Brandsborg et al and the investigators' previous study.
Significant postoperative pain at 24 hours
Time frame: 24 hours after hysterectomy
Numerical pain score (0: no pain; 100: worst pain imaginable) will be assessed at 24 hours after hysterectomy with patient moving from supine to sitting position.
14 secondary outcomes
Central Sensitization Inventory (CSI)
Time frame: 2 months (upon recruitment until before surgery)
Fear Avoidance Components Scale (FACS)
Time frame: 2 months (upon recruitment until before surgery)
Hospital Anxiety and Depression Scale (HADS)
Time frame: 2 months (upon recruitment until before surgery)
Pain Catastrophizing Scale (PCS)
Time frame: 2 months (upon recruitment until before surgery)
Quality of life via EQ-5D
Time frame: 2 months (upon recruitment until before surgery)
Mechanical Temporal Summation (MTS)
Time frame: 2 months (upon recruitment until before surgery)
Pain-Pressure Threshold (PPT)
Time frame: 2 months (upon recruitment until before surgery)
Chronic Post-Hysterectomy Pain at 6 months
Time frame: 6 months after hysterectomy
heart rate variability
Time frame: Preoperative and 24 hours after hysterectomy
Preoperative anxiety
Time frame: Preoperative
State-Trait Anxiety Inventory
Time frame: 2 months (upon recruitment until before surgery)
Beck's Depression Inventory
Time frame: 2 months (upon recruitment until before surgery)
Anticipated pain
Time frame: Preoperative
Anticipated analgesia requirement
Time frame: Preoperative
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2026.
- Background: PubMed 27908839Chapman 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.
- Background: PubMed 28800726Han 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.
- Background: PubMed 23063345Pinto 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.
- Background: PubMed 29628772Sng 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.
- Background: PubMed 25749012Fingleton 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.
- Background: PubMed 23490634Neblett 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.
- Background: PubMed 26228238Neblett 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.
- Background: PubMed 21890662Brandsborg 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Farida Ithnin, MBBS principal investigator
KK Women's and Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hysterectomy and Chronic Pain, run by KK Women's and Children's Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ban Leong Sng, MBBS (+65 6394 1077, sng.ban.leong@singhealth.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Chronic Post-Hysterectomy Pain at 4 months (time frame: 4 months after hysterectomy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04014829, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2026.