Pain Modulation - Experimental Assessments Using Different Modalities

The goal of this study is to investigate how different painful stimuli are processed and modulated in the nervous system. In various pain conditions, including low back pain, often no specific source can be identified as the cause of the pain. Scientific findings point towards a possible involvement of sensitization processes in the central nervous system (spinal cord and brain) that can contribute to the development and persistence of chronic pain. There is a need for reliable and well established experimental methods to better investigate and understand these processes. Frequently used methods comprise the application of thermal, mechanical or electrical stimulations. These modalities are processed in different parts of the nervous system, each allowing its own conclusions. This can be an advantage, but it also poses a challenge regarding comparability and generalizability of obtained results.

This study aims to apply and compare various experimental methods in people without and people with low back pain and shed light on the methodological differences. In the future, this could enable better identification and characterization of sensitization processes in the nervous system and build the basis for individually adapted, mechanism-targeted treatments with better patient outcomes.

Study Overview

• Status: Recruiting
• Conditions: Low Back Pain; Compare Pain Modulation Assessments in Pain-free Cohorts
• Intervention / Treatment: Other: Cold Water Bath; Other: Neutral Water Bath

• Study Type: Interventional
• Enrollment (Anticipated): 705
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Petra Schweinhardt, PhD; Phone Number: +41 44 510 73 81; Email: petra.schweinhardt@balgrist.ch
• Study Contact Backup: Name: Luana Nyirö, DCM; Phone Number: +41 44 386 57 28; Email: luana.nyiroe@balgrist.ch

Study Locations

• Switzerland
  • Zurich, Switzerland, 8008
    • Recruiting
    • Balgrist University Hospital
    • Contact: Petra Schweinhardt, PhD; Phone Number: +41 44 510 73 81; Email: petra.schweinhardt@balgrist.ch
    • Contact: Luana Nyirö, DCM; Phone Number: +41 44 386 57 28; Email: luana.nyiroe@balgrist.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• German or English proficiency
• Informed consent
• primary pain complaint localized between the 12th rib and the gluteal fold
• low back pain for more than one week
• low back pain clinically not attributable to "red flags" (including infection, trauma, fractures, inflammatory)

Exclusion Criteria:

• unable to give informed consent (e.g. due to language problems)
• any neurological condition
• any major medical or psychiatric condition (e.g. severe heart disease, diabetes, autoimmune disorders, major depressive disorder), any chronic pain condition other than low back pain
• pregnancy
• Radiating pain below knee level (radicular pain)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPM - Cold Water Bath	Other: Cold Water Bath; immersion of the hand for 2-5min in 2-10°C water
Sham Comparator: CPM - SHAM	Other: Neutral Water Bath; immersion of the hand for 2-5min in 32±2°C water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temporal Summation of Pain (TSP)	TSP is measured as the change in perceived pain over time in response to repetitive noxious stimulation. In this study, a series of stimulations will be applied using different modalities (pressure, superficial mechanical, heat or electrical stimuli). Participants will be asked to report the perceived pain in response to the stimulations on an 11-point numerical rating scale (0: no pain, 10: most intense pain) or a visual analogue scale (VAS). VAS will be anchored with 0 ("no sensation"), 40 ("just painful," defined as the pain threshold), and 100 ("most intense pain tolerable"). Reflex parameters (thresholds in milliampere (mA); amplitude in μV) will be recorded at start and end of the series. Differences in read-outs (pain ratings, reflex thresholds or reflex amplitudes) at the start of the series compared to the end of the series or the slope of the pain ratings over the series will serve as TSP measures. Greater differences (end-start) or steeper slopes represent a greater TSP.	1-4 weeks
Conditioned Pain Modulation (CPM)	CPM measures the modulation of a noxious test stimulus by another noxious conditioning stimulus applied at a remote body region. In this study, test stimuli of different modalities (pressure, superficial mechanical, heat or electrical stimuli) will be applied at different body regions before and after or before, during and after a cold water bath or neutral water bath (hand immersion) as conditioning stimulus. Changes in test stimuli read-outs (during-before or after-before) will serve as CPM measure. Negative changes represent inhibitory, positive changes facilitatory CPM effects. For all test stimuli read-outs, CPM effects will be expressed as percentage changes. Test stimuli read-outs include: pain ratings (numerical rating scale or VAS, anchors see TSP outcome); perception thresholds (in kg for pressure, millinewton for superficial mechanical, °C for heat and mA for electrical stimuli); pain thresholds; reflex parameters (thresholds in mA and/or amplitudes).	1-4 weeks
CPM effect on TSP	Changes in TSP in response to the intervention (conditioning stimulus: cold water bath or SHAM).	1-4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure sensory and pain sensitivity	Pressure sensitivity will be assessed by for example perception and pain thresholds measured in kg/cm^2. Low thresholds reflect greater sensitivity.	1-4 weeks
Mechanical sensory and pain sensitivity	Mechanical (superficial) sensitivity will be assessed by for example perception and pain thresholds measured in millinewton. Low thresholds reflect greater sensitivity.	1-4 weeks
Heat sensory and pain sensitivity	Heat sensitivity will be assessed by for example perception and pain thresholds measured in °C. Low thresholds reflect greater sensitivity.	1-4 weeks
Electrical sensory and pain sensitivity	Electrical sensitivity will be assessed by for example perception, pain and reflex thresholds measured in milliampere. Low thresholds reflect greater sensitivity.	1-4 weeks
Pain Catastrophizing	Pain catastrophizing will be assessed using questionnaires as for example the Pain Catastrophizing Scale (0-52; higher score meaning more catastrophizing).	1-4 weeks
Fear of pain	Fear of pain will be assessed using questionnaires as for example the Fear Avoidance Belief Questionnaire (0-96) or the Tampa Scale of Kinesiophobia (17-69; higher scores meaning greater fear of pain).	1-4 weeks
Anxiety	Anxiety will be assessed using questionnaires as for example the Spielberger's State and Trait Anxiety Inventory (20-80; higher scores meaning greater anxiety). depression (e.g., Becks Depression Inventory(0-63); higher scores meaning greater level of depression).	1-4 weeks
Depression	Depression will be assessed using questionnaires as for example the Becks Depression Inventory (0-63; higher scores meaning greater level of depression).	1-4 weeks
Pain duration	Low back pain patients will be asked to indicate the duration of their clinical pain in months/years.	1-4 weeks
Spatial pain extent	Low back pain patients will be asked to complete pain drawings indicating painful body regions. The painful body area will be calculated as percentage of the whole body area. Higher percentages represent more widespread pain.	1-4 weeks
Somatic symptoms	Additional questionnaires complementing the psychological construct "pain catastrophizing" are implemented in selected subprojects of the study, e.g., the "Somatic Symptom Scale - 8" (higher score meaning higher somatic symptom burden).	1-4 weeks

Collaborators and Investigators

• Sponsor: Schweinhardt Petra
• Investigators: Principal Investigator: Petra Schweinhardt, PhD, Integrative Spinal Research, Department of Chiropractic Medicine, Balgrist University Hospital, University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Anticipated): May 31, 2025
• Study Completion (Anticipated): May 31, 2025

Study Registration Dates

• First Submitted: March 11, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: low back pain; conditioned pain modulation; temporal summation of pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain
• Other Study ID Numbers: Pain modulation assessments

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No