scholarly journals No relevant differences in conditioned pain modulation effects between parallel and sequential test design. A cross-sectional observational study

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12330
Author(s):  
Roland R. Reezigt ◽  
Sjoerd C. Kielstra ◽  
Michel W. Coppieters ◽  
Gwendolyne G.M. Scholten-Peeters
Keyword(s):  
Test Stimulus ◽  
Stimulus Intensity ◽  
Mechanical Test ◽  
Conditioning Stimulus ◽  
Lower Leg ◽  
Pain Modulation ◽  
Sequential Design ◽  
Stimulus Selection ◽  
Conditioned Pain Modulation ◽  
Parallel Design

Background Conditioned pain modulation (CPM) is measured by comparing pain induced by a test stimulus with pain induced by the same test stimulus, either during (parallel design) or after (sequential design) the conditioning stimulus. Whether design, conditioning stimulus intensity and test stimulus selection affect CPM remains unclear. Methods CPM effects were evaluated in healthy participants (N = 89) at the neck, forearm and lower leg using the cold pressor test as the conditioning stimulus. In three separate experiments, we compared the impact of (1) design (sequential versus parallel), (2) conditioning stimulus intensity (VAS 40/100 versus VAS 60/100), and (3) test stimulus selection (single versus dual, i.e., mechanical and thermal). Statistical analyses of the main effect of design (adjusted for order) and experiment were conducted using linear mixed models with random intercepts. Results No significant differences were identified in absolute CPM data. In relative CPM data, a sequential design resulted in a slightly lower CPM effect compared to a parallel design, and only with a mechanical test stimulus at the neck (−6.1%; 95% CI [−10.1 to −2.1]) and lower leg (−5.9%; 95% CI [−11.7 to −0.1]) but not forearm (−4.5%; 95% CI [−9.0 to 0.1]). Conditioning stimulus intensity and test stimulus selection did not influence the CPM effect nor the difference in CPM effects derived from parallel versus sequential designs. Conclusions Differences in CPM effects between protocols were minimal or absent. A parallel design may lead to a minimally higher relative CPM effect when using a mechanical test stimulus. The conditioning stimulus intensities assessed in this study and performing two test stimuli did not substantially influence the differences between designs nor the magnitude of the CPM effect.

Conditioned pain modulation in rodents can feature hyperalgesia or hypoalgesia depending on test stimulus intensity

Pain ◽  
2019 ◽  
Vol 160 (4) ◽  
pp. 784-792 ◽  
Author(s):  
Shannon N. Tansley ◽  
Leigh C. Macintyre ◽  
Laura Diamond ◽  
Susana G. Sotocinal ◽  
Nicole George ◽  
...  
Keyword(s):  
Test Stimulus ◽  
Stimulus Intensity ◽  
Pain Modulation ◽  
Conditioned Pain Modulation

scholarly journals Development of a new bed-side-test assessing conditioned pain modulation: a test-retest reliability study

2019 ◽  
Vol 19 (3) ◽  
pp. 565-574 ◽  
Author(s):  
Jesper Bie Larsen ◽  
Pascal Madeleine ◽  
Lars Arendt-Nielsen
Keyword(s):  
Test Stimulus ◽  
Conditioning Stimulus ◽  
Pain Modulation ◽  
Clinical Settings ◽  
Conditioned Pain Modulation ◽  
Reliability Study ◽  
Test Protocol ◽  
Bedside Test ◽  
Pressure Algometer ◽  
Test Retest Reliability

Abstract Background and aims Conditioned pain modulation (CPM) is of considerable interest within pain research. Often CPM testing is conducted in experimental settings using complicated instrumentation, thus challenging the implementation in clinical settings. Being able to assess CPM in a fast and reliable way in clinical settings could lead to a new diagnostic tool allowing improved profiling of pain patients. Methods A test-retest reliability study and a methodological development study were conducted based on different populations. The reliability study included 22 healthy subjects, mean age 23.6 years (SD: 2.4) and the methodological study included 29 healthy subjects, mean age 21.5 years (SD: 1.6). As painful phasic test stimulus, a 6–10 kg handheld, spring-based pressure algometer was applied perpendicularly to the muscle belly of the tibialis anterior muscle for 10 s and as painful tonic conditioning stimulus, 1–2 standard clamps, inducing a force of 1.3 kg, were applied extra-segmentally at the ipsilateral earlobe for 60–120 s. Four different test protocols were evaluated, of which one protocol was investigated for reliability. Test protocol 1 used a 6 kg pressure algometer as painful phasic test stimulus and a single clamp applied for 60 s as painful tonic conditioning stimulus. Test protocol 2 used a 10 kg pressure algometer as painful phasic test stimulus, and two clamps applied for 60 s as painful tonic conditioning stimulus. Test protocol 3 used a 10 kg pressure algometer as painful phasic test stimulus and a single clamp applied for 120 s as painful tonic conditioning stimulus. Test protocol 4 used a 6 kg pressure algometer as painful phasic test stimulus and a single clamp applied for 120 s as painful tonic conditioning stimulus. Results None of the stimuli caused any adverse events, e.g. bruises. In the reliability study (test protocol (1), non-significant CPM effects of 0.3 (SD: 1.6) and 0.2 (SD: 1.0) were observed in session 1 and 2, respectively. The intra-class correlations were 0.67 and 0.72 (p = < 0.01) and limits of agreement (LoA) ranged from −2.76 to 3.31. Non-significant CPM effects of 0.2 (SD: 1.0), −0.1 (SD: 1.1), and 0.0 (SD: 1.2) were observed for test protocol 2, 3, and 4, respectively). Conclusions The bedside test developed for investigating CPM was feasible and easy to use in healthy volunteers. No significant CPM effects were measured and a large variation in CPM effect ranging from −0.14 to 0.32 was observed. Intra-class correlation (ICC) values for the pressure algometer were interpreted as “good relative reliability” (test protocol 1), and LoA revealed a somewhat low absolute reliability. Implications The pressure algometer provided reproducible measurements and was useful for inducing phasic test stimuli. Since no significant CPM effects were detected, no recommendations for the bedside test can yet be made. Further examinations will have to establish if the “one size fits all” application of both test and conditioning stimuli is useful. Future bedside studies involving patient populations are warranted to determine the usefulness of the method.

scholarly journals The effect of conditioning stimulus intensity on conditioned pain modulation (CPM) hypoalgesia

2020 ◽  
Author(s):  
Alexia Coulombe-Lévêque ◽  
Yannick Tousignant-Laflamme ◽  
Guillaume Léonard ◽  
Serge Marchand
Keyword(s):  
Stimulus Intensity ◽  
Conditioning Stimulus ◽  
Pain Modulation ◽  
Conditioned Pain Modulation

The Effect of Conditioned Pain Modulation on Tonic Heat Pain Assessed Using Participant-Controlled Temperature

Pain Medicine ◽  
2020 ◽  
Vol 21 (11) ◽  
pp. 2839-2849
Author(s):  
Laura Sirucek ◽  
Catherine Ruth Jutzeler ◽  
Jan Rosner ◽  
Petra Schweinhardt ◽  
Armin Curt ◽  
...  
Keyword(s):  
Test Stimulus ◽  
Temporal Summation ◽  
Pressure Pain Threshold ◽  
Conditioning Stimulus ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Heat Pain ◽  
Pressure Pain ◽  
Withdrawal Reflex ◽  
Pressure Pain Thresholds

Abstract Objective Descending pain modulation can be experimentally assessed by way of testing conditioned pain modulation. The application of tonic heat as a test stimulus in such paradigms offers the possibility of observing dynamic pain responses, such as adaptation and temporal summation of pain. Here we investigated conditioned pain modulation effects on tonic heat employing participant-controlled temperature, an alternative tonic heat pain assessment. Changes in pain perception are thereby represented by temperature adjustments performed by the participant, uncoupling this approach from direct pain ratings. Participant-controlled temperature has emerged as a reliable and sex-independent measure of tonic heat. Methods Thirty healthy subjects underwent a sequential conditioned pain modulation paradigm, in which a cold water bath was applied as the conditioning stimulus and tonic heat as a test stimulus. Subjects were instructed to change the temperature of the thermode in response to variations in perception to tonic heat in order to maintain their initial rating over a two-minute period. Two additional test stimuli (i.e., lower limb noxious withdrawal reflex and pressure pain threshold) were included as positive controls for conditioned pain modulation effects. Results Participant-controlled temperature revealed conditioned pain modulation effects on temporal summation of pain (P = 0.01). Increased noxious withdrawal reflex thresholds (P = 0.004) and pressure pain thresholds (P &lt; 0.001) in response to conditioning also confirmed inhibitory conditioned pain modulation effects. Conclusions The measured interaction between conditioned pain modulation and temporal summation of pain supports the participant-controlled temperature approach as a promising method to explore dynamic inhibitory and facilitatory pain processes previously undetected by rating-based approaches.

Individual variability and sex differences in conditioned pain modulation and the impact of resilience, and conditioning stimulus pain unpleasantness and salience

Pain ◽  
2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Shahrzad Firouzian ◽  
Natalie R. Osborne ◽  
Joshua C. Cheng ◽  
Junseok A. Kim ◽  
Rachael L. Bosma ◽  
...  
Keyword(s):  
Sex Differences ◽  
Conditioning Stimulus ◽  
Individual Variability ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
The Impact ◽  
Pain Unpleasantness

Changes in central delay of soleus H reflex after facilitatory or inhibitory conditioning in humans

1991 ◽  
Vol 65 (6) ◽  
pp. 1598-1605 ◽  
Author(s):  
M. Abbruzzese ◽  
L. Reni ◽  
E. Favale
Keyword(s):  
Test Stimulus ◽  
Stimulus Intensity ◽  
Conditioning Stimulus ◽  
H Reflex ◽  
Reflex Response ◽  
Stimulus Strength ◽  
Inhibitory Conditioning ◽  
The Individual ◽  
Central Delay ◽  
Motoneuronal Pool

1. Central delay (CD) changes after facilitatory or inhibitory conditioning of the soleus H reflex have been investigated in a group of normal subjects as a function of the conditioning and test stimulus intensities and also as a function of the Hmax/Mmax ratio. Both facilitation and inhibition of the reflex response have been obtained by conditioning stimulation of the ipsilateral tibial nerve at suitable conditioning-test stimulus intervals. CD changes have been extrapolated from the variations of the time interval between afferent and efferent neural volleys underlying the H reflex, directly recorded from the sciatic nerve. 2. The CD was significantly decreased by facilitatory and increased by inhibitory conditioning. Facilitatory CD changes were positively related to test stimulus strength (at a given conditioning stimulus intensity) and negatively related to conditioning stimulus strength (at a given test stimulus intensity). Both trends were reversed after inhibitory conditioning. The effectiveness of facilitatory conditioning was positively related to the individual Hmax/Mmax ratio whereas a negative relationship could be observed after inhibitory conditioning. 3. Also, the "conditioning threshold" (the minimal conditioning stimulus strength affecting the reflex size) and the "maximal conditioning effect" (the conditioning stimulus intensities leading to either the saturation of the facilitatory effect or the suppression of the reflex response) were significantly related to the Hmax/Mmax ratio. 4. We suggest that temporal changes in the H reflex pathway after facilitatory or inhibitory conditioning stimuli depend both on the size of the motoneuronal pool underlying the reflex response, as determined by the test stimulus intensity, and on the individual excitability of the motoneuronal pool, as defined by the Hmax/Mmax ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined electric and pressure cuff pain stimuli for assessing conditioning pain modulation (CPM)

2017 ◽  
Vol 16 (1) ◽  
pp. 181-182
Author(s):  
M. Tsukamoto ◽  
K.K. Petersen ◽  
C.D. Mørch ◽  
L. Arendt-Nielsen
Keyword(s):  
Test Stimulus ◽  
Cuff Pressure ◽  
Detection Threshold ◽  
Conditioning Stimulus ◽  
Pain Modulation ◽  
Experimental Site ◽  
Pressure Cuff ◽  
Before And After ◽  
Median Split ◽  
Pain Stimuli

AbstractAimsTraditionally, conditioning pain modulation (CPM) can be assessed by applying a test stimulus (TS) before and after application of a conditioning stimulus (CS), which is normally applied extra-segmental. Currently, no studies have attempted to apply the TS and CS to the same site using different stimuli modalities. The aim of this study was to evaluate electrical TS and cuff pressure CS applied to the same experimental site for studying CPM.Methods20 male volunteers participated in this study, which consisted of stimulations applied by a cuff-algometer (NociTech and Aalborg University, Denmark) and current stimulator (Digitimer DS5, UK), through two Ag/AgCl electrodes (Ambu® Neuroline 700, Denmark). The cuff was wrapped around the lower leg and stimulation electrodes were placed under the cuff and to the same location on the contralateral leg. Electrical TS were applied to the non-dominant leg with or without cuff pressure CS on the dominant (CS1) or the same (non-dominant) leg (CS2, electrode under cuff). The subjects were instructed to rate the electrical evoked pain intensity on a 10-cm continuous visual analog scale (VAS, “0” represented “no pain”, and “10” represented “maximal pain”). The pain detection threshold (PDT) was defined as “1” on the VAS scale.ResultsThere was no significant deference in PDT for neither CS1 nor CS2. A median split subanalysis on CPM-responders versus CPM-nonresponders to the TS + CS1 combination. Using this grouping, there was significant increase in PDT when comparing TS to TS + CS1 or TS + CS2 (4.0 mA vs 5.6 mA; P < 0.05, 4.0 mA vs 5.1 mA; P < 0.05).ConclusionsThe study indicates that CPM can be evoked in a subgroup of subjects by applying the electrical test stimulus and cuff pressure conditioning stimuli to the same experimental site.

scholarly journals The Potential Clinical Utility of Pressure-Based vs. Heat-Based Paradigms to Measure Conditioned Pain Modulation in Healthy Individuals and Those With Chronic Pain

2021 ◽  
Vol 2 ◽  
Author(s):  
Rima El-Sayed ◽  
Camille Fauchon ◽  
Junseok A. Kim ◽  
Shahrzad Firouzian ◽  
Natalie R. Osborne ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Pain Intensity ◽  
Pain Treatment ◽  
Detection Threshold ◽  
Conditioning Stimulus ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Healthy Individuals ◽  
Significant Difference ◽  
Clinical Adoption

Conditioned pain modulation (CPM) is a physiological measure thought to reflect an individual's endogenous pain modulation system. CPM varies across individuals and provides insight into chronic pain pathophysiology. There is growing evidence that CPM may help predict individual pain treatment outcome. However, paradigm variabilities and practical issues have impeded widespread clinical adoption of CPM assessment. This study aimed to compare two CPM paradigms in people with chronic pain and healthy individuals. A total of 30 individuals (12 chronic pain, 18 healthy) underwent two CPM paradigms. The heat CPM paradigm acquired pain intensity ratings evoked by a test stimulus (TS) applied before and during the conditioning stimulus (CS). The pressure CPM paradigm acquired continuous pain intensity ratings of a gradually increasing TS, before and during CS. Pain intensity was rated from 0 (no pain) to 100 (worst pain imaginable); Pain50 is the stimulus level for a response rated 50. Heat and pressure CPM were calculated as a change in TS pain intensity ratings at Pain50, where negative CPM scores indicate pain inhibition. We also determined CPM in the pressure paradigm as change in pressure pain detection threshold (PDT). We found that in healthy individuals the CPM effect was significantly more inhibitory using the pressure paradigm than the heat paradigm. The pressure CPM effect was also significantly more inhibitory when based on changes at Pain50 than at PDT. However, in individuals with chronic pain there was no significant difference in pressure CPM compared to heat or PDT CPM. There was no significant correlation between clinical pain measures (painDETECT and Brief Pain Inventory) and paradigm type (heat vs. pressure), although heat-based CPM and painDETECT scores showed a trend. Importantly, the pressure paradigm could be administered in less time than the heat paradigm. Thus, our study indicates that in healthy individuals, interpretation of CPM findings should consider potential modality-dependent effects. However, in individuals with chronic pain, either heat or pressure paradigms can similarly be used to assess CPM. Given the practical advantages of the pressure paradigm (e.g., short test time, ease of use), we propose this approach to be well-suited for clinical adoption.

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