Assessment of CPM reliability: quantification of the within-subject reliability of 10 different protocols

Henrik Bjarke Vaegter, Kristian Kjær Petersen, Carsten Dahl Mørch, Yosuke Imai, Lars Arendt-Nielsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Resumé

Background and aims Conditioned Pain Modulation (CPM) is a well-established phenomenon and several protocols have shown acceptable between-subject reliability [based on intraclass correlation coefficient (ICC) values] in pain-free controls. Recently, it was recommended that future CPM test-retest reliability studies should explicitly report CPM reliability based on CPM responders and non-responders (within-subject reliability) based on measurement error of the test stimulus. Identification of reliable CPM paradigms based on responders and non-responders may be a step towards using CPM as a mechanistic marker in diagnosis and individualized pain management regimes. The primary aim of this paper is to investigate the frequency of CPM responders/non-responders, and to quantify the agreements in the classification of responders/non-responders between 2 different days for 10 different CPM protocols. Methods Data from a previous study investigating reliability of CPM protocols in healthy subjects was used. In 26 healthy men, the test-stimuli used on both days were: Pain thresholds to electrical stimulation, heat stimulation, manual algometry, and computer-controlled cuff algometry as well as pain tolerance to cuff algometry. Two different conditioning stimuli (CS; cold water immersion and a computer-controlled tourniquet) were used in a randomized and counterbalanced order in both sessions. CPM responders were defined as a larger increase in the test stimulus response during the CS than the standard error of measurement (SEM) for the test-stimuli between repeated baseline tests without CS. Results Frequency of responders and non-responders showed large variations across protocols. Across the studied CPM protocols, a large proportion (from 11.5 to 73.1%) of subjects was classified as CPM non-responders when the test stimuli standard error of measurements (SEM) was considered as classifier. The combination of manual pressure algometry and cold water immersion induced a CPM effect in most participants on both days (n=16). However, agreement in the classification of CPM responders versus non-responders between days was only significant when assessed with computer-controlled pressure pain threshold as test-stimulus and tourniquet cuff as CS (κ=0.36 [95% CI, 0.04-0.68], p=0.037). Conclusions and implications Agreements in classification of CPM responders/non-responders using SEM as classifier between days were generally poor suggesting considerable intra-individual variation in CPM. The most reliable paradigm was computer-controlled pressure pain threshold as test-stimulus and tourniquet cuff as conditioning stimulus. However while this CPM protocol had the greatest degree of agreement of classification of CPM responders and non-responders across days, this protocol also failed to induce a CPM response in more than half of the sample. In contrast, the commonly used combination of manual pressure algometry and cold water immersion induced a CPM effect in most participants however it was inconsistent in doing so. Further exploration of the two paradigms and classification of responders and non-responders in a larger heterogeneous sample also including women would further inform the clinical usefulness of these CPM protocols. Future research in this area may be an important step towards using CPM as a mechanistic marker in diagnosis and in developing individualized pain management regimes.

OriginalsprogEngelsk
TidsskriftScandinavian Journal of Pain
Vol/bind18
Udgave nummer4
Sider (fra-til)729–737
ISSN1877-8860
DOI
StatusUdgivet - 25. okt. 2018

Fingeraftryk

Pain Measurement
Pain Threshold
Immersion
Pain Management

Citer dette

Vaegter, Henrik Bjarke ; Petersen, Kristian Kjær ; Mørch, Carsten Dahl ; Imai, Yosuke ; Arendt-Nielsen, Lars. / Assessment of CPM reliability : quantification of the within-subject reliability of 10 different protocols. I: Scandinavian Journal of Pain. 2018 ; Bind 18, Nr. 4. s. 729–737.
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title = "Assessment of CPM reliability: quantification of the within-subject reliability of 10 different protocols",
abstract = "Background and aims Conditioned Pain Modulation (CPM) is a well-established phenomenon and several protocols have shown acceptable between-subject reliability [based on intraclass correlation coefficient (ICC) values] in pain-free controls. Recently, it was recommended that future CPM test-retest reliability studies should explicitly report CPM reliability based on CPM responders and non-responders (within-subject reliability) based on measurement error of the test stimulus. Identification of reliable CPM paradigms based on responders and non-responders may be a step towards using CPM as a mechanistic marker in diagnosis and individualized pain management regimes. The primary aim of this paper is to investigate the frequency of CPM responders/non-responders, and to quantify the agreements in the classification of responders/non-responders between 2 different days for 10 different CPM protocols. Methods Data from a previous study investigating reliability of CPM protocols in healthy subjects was used. In 26 healthy men, the test-stimuli used on both days were: Pain thresholds to electrical stimulation, heat stimulation, manual algometry, and computer-controlled cuff algometry as well as pain tolerance to cuff algometry. Two different conditioning stimuli (CS; cold water immersion and a computer-controlled tourniquet) were used in a randomized and counterbalanced order in both sessions. CPM responders were defined as a larger increase in the test stimulus response during the CS than the standard error of measurement (SEM) for the test-stimuli between repeated baseline tests without CS. Results Frequency of responders and non-responders showed large variations across protocols. Across the studied CPM protocols, a large proportion (from 11.5 to 73.1{\%}) of subjects was classified as CPM non-responders when the test stimuli standard error of measurements (SEM) was considered as classifier. The combination of manual pressure algometry and cold water immersion induced a CPM effect in most participants on both days (n=16). However, agreement in the classification of CPM responders versus non-responders between days was only significant when assessed with computer-controlled pressure pain threshold as test-stimulus and tourniquet cuff as CS (κ=0.36 [95{\%} CI, 0.04-0.68], p=0.037). Conclusions and implications Agreements in classification of CPM responders/non-responders using SEM as classifier between days were generally poor suggesting considerable intra-individual variation in CPM. The most reliable paradigm was computer-controlled pressure pain threshold as test-stimulus and tourniquet cuff as conditioning stimulus. However while this CPM protocol had the greatest degree of agreement of classification of CPM responders and non-responders across days, this protocol also failed to induce a CPM response in more than half of the sample. In contrast, the commonly used combination of manual pressure algometry and cold water immersion induced a CPM effect in most participants however it was inconsistent in doing so. Further exploration of the two paradigms and classification of responders and non-responders in a larger heterogeneous sample also including women would further inform the clinical usefulness of these CPM protocols. Future research in this area may be an important step towards using CPM as a mechanistic marker in diagnosis and in developing individualized pain management regimes.",
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year = "2018",
month = "10",
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Assessment of CPM reliability : quantification of the within-subject reliability of 10 different protocols. / Vaegter, Henrik Bjarke; Petersen, Kristian Kjær; Mørch, Carsten Dahl; Imai, Yosuke; Arendt-Nielsen, Lars.

I: Scandinavian Journal of Pain, Bind 18, Nr. 4, 25.10.2018, s. 729–737.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Assessment of CPM reliability

T2 - quantification of the within-subject reliability of 10 different protocols

AU - Vaegter, Henrik Bjarke

AU - Petersen, Kristian Kjær

AU - Mørch, Carsten Dahl

AU - Imai, Yosuke

AU - Arendt-Nielsen, Lars

PY - 2018/10/25

Y1 - 2018/10/25

N2 - Background and aims Conditioned Pain Modulation (CPM) is a well-established phenomenon and several protocols have shown acceptable between-subject reliability [based on intraclass correlation coefficient (ICC) values] in pain-free controls. Recently, it was recommended that future CPM test-retest reliability studies should explicitly report CPM reliability based on CPM responders and non-responders (within-subject reliability) based on measurement error of the test stimulus. Identification of reliable CPM paradigms based on responders and non-responders may be a step towards using CPM as a mechanistic marker in diagnosis and individualized pain management regimes. The primary aim of this paper is to investigate the frequency of CPM responders/non-responders, and to quantify the agreements in the classification of responders/non-responders between 2 different days for 10 different CPM protocols. Methods Data from a previous study investigating reliability of CPM protocols in healthy subjects was used. In 26 healthy men, the test-stimuli used on both days were: Pain thresholds to electrical stimulation, heat stimulation, manual algometry, and computer-controlled cuff algometry as well as pain tolerance to cuff algometry. Two different conditioning stimuli (CS; cold water immersion and a computer-controlled tourniquet) were used in a randomized and counterbalanced order in both sessions. CPM responders were defined as a larger increase in the test stimulus response during the CS than the standard error of measurement (SEM) for the test-stimuli between repeated baseline tests without CS. Results Frequency of responders and non-responders showed large variations across protocols. Across the studied CPM protocols, a large proportion (from 11.5 to 73.1%) of subjects was classified as CPM non-responders when the test stimuli standard error of measurements (SEM) was considered as classifier. The combination of manual pressure algometry and cold water immersion induced a CPM effect in most participants on both days (n=16). However, agreement in the classification of CPM responders versus non-responders between days was only significant when assessed with computer-controlled pressure pain threshold as test-stimulus and tourniquet cuff as CS (κ=0.36 [95% CI, 0.04-0.68], p=0.037). Conclusions and implications Agreements in classification of CPM responders/non-responders using SEM as classifier between days were generally poor suggesting considerable intra-individual variation in CPM. The most reliable paradigm was computer-controlled pressure pain threshold as test-stimulus and tourniquet cuff as conditioning stimulus. However while this CPM protocol had the greatest degree of agreement of classification of CPM responders and non-responders across days, this protocol also failed to induce a CPM response in more than half of the sample. In contrast, the commonly used combination of manual pressure algometry and cold water immersion induced a CPM effect in most participants however it was inconsistent in doing so. Further exploration of the two paradigms and classification of responders and non-responders in a larger heterogeneous sample also including women would further inform the clinical usefulness of these CPM protocols. Future research in this area may be an important step towards using CPM as a mechanistic marker in diagnosis and in developing individualized pain management regimes.

AB - Background and aims Conditioned Pain Modulation (CPM) is a well-established phenomenon and several protocols have shown acceptable between-subject reliability [based on intraclass correlation coefficient (ICC) values] in pain-free controls. Recently, it was recommended that future CPM test-retest reliability studies should explicitly report CPM reliability based on CPM responders and non-responders (within-subject reliability) based on measurement error of the test stimulus. Identification of reliable CPM paradigms based on responders and non-responders may be a step towards using CPM as a mechanistic marker in diagnosis and individualized pain management regimes. The primary aim of this paper is to investigate the frequency of CPM responders/non-responders, and to quantify the agreements in the classification of responders/non-responders between 2 different days for 10 different CPM protocols. Methods Data from a previous study investigating reliability of CPM protocols in healthy subjects was used. In 26 healthy men, the test-stimuli used on both days were: Pain thresholds to electrical stimulation, heat stimulation, manual algometry, and computer-controlled cuff algometry as well as pain tolerance to cuff algometry. Two different conditioning stimuli (CS; cold water immersion and a computer-controlled tourniquet) were used in a randomized and counterbalanced order in both sessions. CPM responders were defined as a larger increase in the test stimulus response during the CS than the standard error of measurement (SEM) for the test-stimuli between repeated baseline tests without CS. Results Frequency of responders and non-responders showed large variations across protocols. Across the studied CPM protocols, a large proportion (from 11.5 to 73.1%) of subjects was classified as CPM non-responders when the test stimuli standard error of measurements (SEM) was considered as classifier. The combination of manual pressure algometry and cold water immersion induced a CPM effect in most participants on both days (n=16). However, agreement in the classification of CPM responders versus non-responders between days was only significant when assessed with computer-controlled pressure pain threshold as test-stimulus and tourniquet cuff as CS (κ=0.36 [95% CI, 0.04-0.68], p=0.037). Conclusions and implications Agreements in classification of CPM responders/non-responders using SEM as classifier between days were generally poor suggesting considerable intra-individual variation in CPM. The most reliable paradigm was computer-controlled pressure pain threshold as test-stimulus and tourniquet cuff as conditioning stimulus. However while this CPM protocol had the greatest degree of agreement of classification of CPM responders and non-responders across days, this protocol also failed to induce a CPM response in more than half of the sample. In contrast, the commonly used combination of manual pressure algometry and cold water immersion induced a CPM effect in most participants however it was inconsistent in doing so. Further exploration of the two paradigms and classification of responders and non-responders in a larger heterogeneous sample also including women would further inform the clinical usefulness of these CPM protocols. Future research in this area may be an important step towards using CPM as a mechanistic marker in diagnosis and in developing individualized pain management regimes.

KW - conditioned pain modulation

KW - cuff algometry

KW - pain sensitivity

KW - pain threshold

KW - pain tolerance

KW - reliability

KW - test-retest

U2 - 10.1515/sjpain-2018-0087

DO - 10.1515/sjpain-2018-0087

M3 - Journal article

C2 - 30007061

VL - 18

SP - 729

EP - 737

JO - Scandinavian Journal of Pain

JF - Scandinavian Journal of Pain

SN - 1877-8860

IS - 4

ER -