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

NCT ID: NCT04014829

Last Updated: 2024-11-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

436 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-07-23

Study Completion Date

2027-12-31

Brief Summary

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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

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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.

Conditions

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Hysterectomy Chronic Pain Central Sensitisation Anxiety Depression

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Pain-Pressure Threshold

Intervention Type DIAGNOSTIC_TEST

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 Summation

Intervention Type DIAGNOSTIC_TEST

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 Scale

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of anxiety and depression.

Pain Catastrophizing Scale

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of pain catastrophizing.

Central Sensitization Inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of central sensitization.

Fear-Avoidance Component Score

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of fear and avoidance.

EQ-5D

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess generic health-related quality of life.

heart rate variability

Intervention Type DIAGNOSTIC_TEST

Heart rate variability will be determined from the R-to-R intervals obtained from a 5-minute ECG recording.

Anxiety, anticipated pain, anticipated analgesia

Intervention Type DIAGNOSTIC_TEST

Preoperative anxiety (0 to 100), anticipated pain (0 to 100), and anticipated analgesia requirement (0 to 5).

State-trait anxiety inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess anxiety.

Beck's Depression Inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess depressive symptoms.

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.

Pain-Pressure Threshold

Intervention Type DIAGNOSTIC_TEST

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 Summation

Intervention Type DIAGNOSTIC_TEST

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 Scale

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of anxiety and depression.

Pain Catastrophizing Scale

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of pain catastrophizing.

Central Sensitization Inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of central sensitization.

Fear-Avoidance Component Score

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of fear and avoidance.

EQ-5D

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess generic health-related quality of life.

heart rate variability

Intervention Type DIAGNOSTIC_TEST

Heart rate variability will be determined from the R-to-R intervals obtained from a 5-minute ECG recording.

Anxiety, anticipated pain, anticipated analgesia

Intervention Type DIAGNOSTIC_TEST

Preoperative anxiety (0 to 100), anticipated pain (0 to 100), and anticipated analgesia requirement (0 to 5).

State-trait anxiety inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess anxiety.

Beck's Depression Inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess depressive symptoms.

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.

Pain-Pressure Threshold

Intervention Type DIAGNOSTIC_TEST

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 Summation

Intervention Type DIAGNOSTIC_TEST

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 Scale

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of anxiety and depression.

Pain Catastrophizing Scale

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of pain catastrophizing.

Central Sensitization Inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of central sensitization.

Fear-Avoidance Component Score

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of fear and avoidance.

EQ-5D

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess generic health-related quality of life.

heart rate variability

Intervention Type DIAGNOSTIC_TEST

Heart rate variability will be determined from the R-to-R intervals obtained from a 5-minute ECG recording.

Anxiety, anticipated pain, anticipated analgesia

Intervention Type DIAGNOSTIC_TEST

Preoperative anxiety (0 to 100), anticipated pain (0 to 100), and anticipated analgesia requirement (0 to 5).

State-trait anxiety inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess anxiety.

Beck's Depression Inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess depressive symptoms.

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.

Pain-Pressure Threshold

Intervention Type DIAGNOSTIC_TEST

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 Summation

Intervention Type DIAGNOSTIC_TEST

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 Scale

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of anxiety and depression.

Pain Catastrophizing Scale

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of pain catastrophizing.

Central Sensitization Inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of central sensitization.

Fear-Avoidance Component Score

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to determine the level of fear and avoidance.

EQ-5D

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess generic health-related quality of life.

heart rate variability

Intervention Type DIAGNOSTIC_TEST

Heart rate variability will be determined from the R-to-R intervals obtained from a 5-minute ECG recording.

Anxiety, anticipated pain, anticipated analgesia

Intervention Type DIAGNOSTIC_TEST

Preoperative anxiety (0 to 100), anticipated pain (0 to 100), and anticipated analgesia requirement (0 to 5).

State-trait anxiety inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess anxiety.

Beck's Depression Inventory

Intervention Type DIAGNOSTIC_TEST

Standardized questionnaire to assess depressive symptoms.

Interventions

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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.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Hospital Anxiety and Depression Scale

Standardized questionnaire to determine the level of anxiety and depression.

Intervention Type DIAGNOSTIC_TEST

Pain Catastrophizing Scale

Standardized questionnaire to determine the level of pain catastrophizing.

Intervention Type DIAGNOSTIC_TEST

Central Sensitization Inventory

Standardized questionnaire to determine the level of central sensitization.

Intervention Type DIAGNOSTIC_TEST

Fear-Avoidance Component Score

Standardized questionnaire to determine the level of fear and avoidance.

Intervention Type DIAGNOSTIC_TEST

EQ-5D

Standardized questionnaire to assess generic health-related quality of life.

Intervention Type DIAGNOSTIC_TEST

heart rate variability

Heart rate variability will be determined from the R-to-R intervals obtained from a 5-minute ECG recording.

Intervention Type DIAGNOSTIC_TEST

Anxiety, anticipated pain, anticipated analgesia

Preoperative anxiety (0 to 100), anticipated pain (0 to 100), and anticipated analgesia requirement (0 to 5).

Intervention Type DIAGNOSTIC_TEST

State-trait anxiety inventory

Standardized questionnaire to assess anxiety.

Intervention Type DIAGNOSTIC_TEST

Beck's Depression Inventory

Standardized questionnaire to assess depressive symptoms.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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PPT MTS HADS PCS CSI FACS HRV STAI BDI

Eligibility Criteria

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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
Minimum Eligible Age

21 Years

Maximum Eligible Age

80 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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KK Women's and Children's Hospital

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Farida Ithnin, MBBS

Role: PRINCIPAL_INVESTIGATOR

KK Women's and Children's Hospital

Locations

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KK Women's and Children's Hospital

Singapore, , Singapore

Site Status RECRUITING

Countries

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Singapore

Central Contacts

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Ban Leong Sng, MBBS

Role: CONTACT

+65 6394 1077

Hon Sen Tan, MD

Role: CONTACT

+65 9365 7193

Facility Contacts

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Hon Sen Tan, MD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 27908839 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28800726 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23063345 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29628772 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25749012 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23490634 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26228238 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21890662 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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EPOCH

Identifier Type: -

Identifier Source: org_study_id

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