Reliability of the conditioned pain modulation paradigm across three anatomical sites

2020 ◽  
Vol 20 (2) ◽  
pp. 283-296
Author(s):  
Rania Nuwailati ◽  
Michele Curatolo ◽  
Linda LeResche ◽  
Douglas S. Ramsay ◽  
Charles Spiekerman ◽  
...  
Keyword(s):  
Cold Pressor Test ◽  
Pressure Pain Threshold ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Dominant Hand ◽  
Pain Mechanisms ◽  
Relative Reliability ◽  
Contralateral Hand ◽  
The Face ◽  
Absolute Reliability

AbstractBackground and aimsConditioned Pain Modulation (CPM) is a measure of pain inhibition-facilitation in humans that may elucidate pain mechanisms and potentially serve as a diagnostic test. In laboratory settings, the difference between two pain measures [painful test stimulus (TS) without and with the conditioning stimulus (CS) application] reflects the CPM magnitude. Before the CPM test can be used as a diagnostic tool, its reliability on the same day (intra-session) and across multiple days (inter-session) needs to be known. Furthermore, it is important to determine the most reliable anatomical sites for both the TS and the CS. This study aimed to measure the intra-session and inter-session reliability of the CPM test paradigm in healthy subjects with the TS (pressure pain threshold-PPT) applied to three test sites: the face, hand, and dorsum of the foot, and the CS (cold pressor test-CPT) applied to the contralateral hand.MethodsSixty healthy participants aged 18–65 were tested by the same examiner on 3 separate days, with an interval of 2–7 days. On each day, testing was comprised of two identical experimental sessions in which the PPT test was performed on each of the three dominant anatomical sites in randomized order followed by the CPM test (repeating the PPT with CPT on the non-dominant hand). CPM magnitude was calculated as the percent change in PPT. The Intraclass Correlation Coefficient (ICC), Coefficient of Variation (CV), and Bland-Altman analyses were used to assess reliability.ResultsPPT relative reliability ranged from good to excellent at all three sites; the hand showed an intra-session ICC of 0.90 (0.84, 0.94) before CPT and ICC of 0.89 (0.83, 0.92) during CPT. The PPT absolute reliability was also high, showing a low bias and small variability when performed on all three sites; for example, CV of the hand intra-session was 8.0 before CPT and 8.1 during CPT. The relative reliability of the CPM test, although only fair, was most reliable when performed during the intra-session visits on the hand; ICC of 0.57 (0.37, 0.71) vs. 0.20 (0.03, 0.39) for the face, and 0.22 (0.01, 0.46) for the foot. The inter-session reliability was lower in all three anatomical sites, with the best reliability on the hand with an ICC of 0.40 (0.23, 0.55). The pattern of absolute reliability of CPM was similar to the relative reliability findings, with the reliability best on the hand, showing lower intra-session and inter-session variability (CV% = 43.5 and 51.5, vs. 70.1 and 73.1 for the face, and 75.9 and 78.9 for the foot). The CPM test was more reliable in women than in men, and in older vs. younger participants.DiscussionThe CPM test was most reliable when the TS was applied to the dominant hand and CS performed on the contralateral hand. These data indicate that using the CS and TS in the same but contralateral dermatome in CPM testing may create the most reliable results.

scholarly journals Conditioned Pain Modulation Is Not Impaired in Individuals with Frozen Shoulder: A Case-Control Study

2021 ◽  
Vol 18 (23) ◽  
pp. 12330
Author(s):  
Marta Aguilar-Rodríguez ◽  
Lirios Dueñas ◽  
Mercè Balasch i Bernat ◽  
Mira Meeus ◽  
Filip Struyf ◽  
...  
Keyword(s):  
Frozen Shoulder ◽  
Pressure Pain Threshold ◽  
Conditioning Stimulus ◽  
Cross Sectional Study ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Central Pain ◽  
Cross Sectional ◽  
Pain Mechanisms ◽  
The Absolute

Frozen shoulder (FS) is a poorly understood condition resulting in substantial shoulder pain and mobility deficits. The mechanisms behind FS are not yet fully understood, but, similar to other persistent pain states, central pain mechanisms may contribute to ongoing symptoms in this population. The objective of this research was to investigate conditioned pain modulation (CPM) in people with FS compared with pain-free individuals. A total of 64 individuals with FS and 64 healthy volunteers participated in this cross-sectional study. CPM was assessed by using the pressure pain threshold (PPT) and an occlusion cuff (tourniquet test) as the test and conditioning stimulus, respectively. The absolute and percentage of change in PPT (CPM effect) as well as pain profiles (pro-nociceptive vs. anti-nociceptive) of individuals with FS and healthy controls were calculated. No significant differences in the absolute change in the PPT or CPM effect were found in people with FS compared to pain-free controls. Moreover, no between-group differences in the percentage of subjects with pro-nociceptive and anti-nociceptive pain profiles were observed. These results suggest that endogenous pain inhibition is normally functioning in people with FS. Altered central pain-processing mechanisms may thus not be a characteristic of this population.

scholarly journals Reliability of the Conditioned Pain Modulation Paradigm to Assess Endogenous Inhibitory Pain Pathways

2012 ◽  
Vol 17 (2) ◽  
pp. 98-102 ◽  
Author(s):  
Gwyn N Lewis ◽  
Heales Luke ◽  
David A Rice ◽  
Keith Rome ◽  
Peter J McNair
Keyword(s):  
Pain Threshold ◽  
Intraclass Correlation ◽  
Cold Pressor Test ◽  
Pressure Pain Threshold ◽  
Cold Pressor ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Pressure Pain ◽  
Pressor Test ◽  
Conditioning Stimuli

BACKGROUND: Conditioned pain modulation paradigms are often used to assess the diffuse noxious inhibitory control (DNIC) system. DNICs provide one of the main supraspinal pain inhibitory pathways and are impaired in several chronic pain populations. Only one previous study has examined the psychometric properties of the conditioned pain modulation technique and this study did not evaluate intersession reliability.OBJECTIVES: To evaluate and compare the intra- and intersession reliability of two conditioned pain modulation paradigms using different conditioning stimuli, and to determine the time course of conditioned pain inhibition following stimulus removal.METHODS: An electronic pressure transducer was used to determine the pressure-pain threshold at the knee during painful conditioning of the opposite hand using the ischemic arm test and the cold pressor test. Assessments were completed twice on one day and repeated once approximately three days later.RESULTS: The two conditioning stimuli resulted in a similar increase in the pressure-pain threshold at the knee, reflecting presumed activation of the DNIC system. Intrasession intraclass correlation coefficients for the cold pressor (0.85) and ischemic arm tests (0.75) were excellent. The intersession intraclass correlation coefficient for the cold pressor test was good (0.66) but was poor for the ischemic arm test (−0.4). Inhibition of the pressure-pain threshold remained significant at 10 min following conditioning, but returned to baseline by 15 min.CONCLUSIONS: Within-session reliability of DNIC assessment using conditioned pain modulation paradigms was excellent, but the applicability of assessing pain modulation over multiple sessions was influenced by the conditioning stimulus. The cold pressor test was the superior technique.

Central and peripheral pain sensitization during an ultra-marathon competition

2018 ◽  
Vol 18 (4) ◽  
pp. 703-709 ◽  
Author(s):  
James W. Agnew ◽  
Steven B. Hammer ◽  
Alexandre L. Roy ◽  
Amina Rahmoune
Keyword(s):  
Pain Threshold ◽  
Pressure Pain Threshold ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Central Pain ◽  
Dominant Hand ◽  
Pressure Pain ◽  
Peripheral Pain ◽  
Pain Sensitization ◽  
Ultra Endurance

Abstract Background and aims The participation in ultra-marathons and other ultra-endurance events has increased exponentially over the past decade. There is insufficient data on variation in pain mechanisms in exercise overall but especially in the ultra-endurance athlete population. To further understand peripheral and central pain sensitization we have investigated pressure pain threshold and conditioned pain modulation during three separate ultra-marathon competitions. Methods Each ultra-marathon investigated was held in the state of Florida, USA, over flat, sandy and paved surfaces under generally warm to hot, humid conditions. Pressure pain threshold was measured utilizing a Baseline © Dolorimeter. The blunt end of the dolorimeter stylus was placed onto the distal dominant arm, equidistant between the distal radius and ulna, three times in a blinded manner to insure that the testing technician did not influence the subject’s responses. Conditioned pain modulation was measured immediately after the PPT measures by placing the non-dominant hand in a cool water bath maintained at 15°C. The same dolorimeter measurement was repeated two more times on the dominant arm while the non-dominant hand remained in the water. Data was analyzed with a paired t-test. Results Pressure pain threshold was significantly decreased (p<0.05) at 25, 50 and 100 miles. Conditioned pain modulation was also significantly decreased (p<0.05) at 25, 50 and 100 miles of an ultra-marathon competition. Conclusions Together these data suggest an increased peripheral and/or central pain sensitization starting at 25 miles and continuing throughout an ultra-marathon competition run in these conditions. This is the first study that provides evidence of a decreased peripheral pain threshold and decreased central pain inhibition from ultra-marathon running. Decreases in both the peripheral pain threshold and central inhibition may result from nociceptor plasticity, central sensitization or a combination of both. Implications Based on previous research that has indicated a central sensitization resulting from inflammation and the well-documented inflammatory response to the rigors of ultra-marathon competition, we suggest the decreased peripheral pain threshold and decreased descending pain inhibition results from this inflammatory response of running an ultra-marathon.

REPRINTED WITH PERMISSION OF IASP – PAIN 160 (2019) 2679–2690: Conditioned pain modulation as a biomarker of chronic pain: a systematic review of its concurrent validity

Ból ◽  
2020 ◽  
Vol 21 (3) ◽  
pp. 1-15
Author(s):  
Carina Fernandes ◽  
Marina Pidal-Miranda ◽  
Noelia Samartin-Veiga ◽  
María T. Carrillo-de-la-Peña
Keyword(s):  
Systematic Review ◽  
Chronic Pain ◽  
Concurrent Validity ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Experimental Pain ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Pain Mechanisms ◽  
Chronic Pain Conditions

Conditioned pain modulation (CPM) is a promising psychophysical biomarker of central pain mechanisms because it significantly discriminates patients with chronic pain from healthy controls. Nevertheless, it is unclear in what extent CPM assessed experimentally is correlated with clinical manifestations of pain. To assess the concurrent validity of CPM, we performed a systematic review of the literature reporting correlations between CPM responses and pain intensity, disability, duration, and area in patients with different chronic pain conditions. We included 32 studies that altogether encompassed data from 1958 patients and provided 62 correlations. The majority of the results (69%) reported nonsignificant correlations between CPM efficiency and clinical manifestations of pain, whereas the remaining results showed a correlation between CPM reduction and worse clinical symptoms of pain. The modality of stimulation, the type of pain, and the stimulation site appear to be critical variables that influenced the pattern of results. Given that most of the studies were conducted with highly heterogeneous methodologies and unclear risk of bias, the findings highlight the need for future studies using standardized measures of clinical and experimental pain before considering CPM as a valid biomarker of pain. We discuss some guidelines to overcome the constraints in this promising line of research.

scholarly journals Physical Activity May Be Associated with Conditioned Pain Modulation in Women but Not Men among Healthy Individuals

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yukiko Shiro ◽  
Tatsunori Ikemoto ◽  
Yuta Terasawa ◽  
Young-Chang P. Arai ◽  
Kazuhiro Hayashi ◽  
...  
Keyword(s):  
Physical Activity ◽  
Vigorous Physical Activity ◽  
Pressure Pain Threshold ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Mechanical Pressure ◽  
Cold Stimulation ◽  
Entire Study ◽  
Young Subjects ◽  
Study Participants

Background. Conditioned pain modulation (CPM), a phenomenon also known as diffuse noxious inhibitory control, is thought to be affected by various factors, including sex and level of physical activity. However, the involvement of these factors in CPM remains unclear. Methods. Eighty-six healthy young subjects (M/F, 43/43) participated in this study. Participants were assessed on the basis of their mechanical pressure pain threshold (PPT), CPM response, body mass index (BMI), basal metabolic rate (BMR), and duration of moderate-to-vigorous physical activity (MVPA) over a week, using a motion counter. Response to CPM was evaluated as PPT during painful cold stimulation relative to baseline PPT. Results. Men showed significantly higher baseline PPT than women; however, this difference was no longer significant after controlling for confounders. Stepwise multiple linear regression analyses revealed BMR to be a significant contributor towards baseline PPT in the entire study population. In contrast, although there were no significant contributors to CPM response among men and in the overall study group, MVPA was positively associated with CPM response among women (β = 0.397). Conclusions. These results suggest that, among healthy young individuals, CPM response may be associated with moderate-to-vigorous physical activity in women but not in men.

Effects of conditioned pain modulation on the withdrawal pattern to nociceptive stimulation in humans – Preliminary results

2017 ◽  
Vol 16 (1) ◽  
pp. 176-177
Author(s):  
F.A. Jure ◽  
F.G. Arguissain ◽  
J.A. Biurrun Manresa ◽  
O.K. Andersen
Keyword(s):  
Cold Water ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Biceps Femoris ◽  
Pain Modulation ◽  
Wilcoxon Test ◽  
Conditioned Pain Modulation ◽  
Stimulus Interval ◽  
Biceps Femoris Muscle ◽  
Femoris Muscle

AbstractAimsConditioned pain modulation (CPM) is a paradigm employed to assess descending control of spinal nociception. Previous studies have shown that CPM affects the nociceptive withdrawal reflex (NWR) threshold (RTh), typically assessed in one muscle. However, the NWR activates not one but a group of synergistic muscles, which are recruited by common neural commands to achieve the limb withdrawal. In this regard, synergy analysis can provide the minimum coordinated recruitment of groups of muscles with specific activation balances that describe a movement. The aim was to assess how CPM modulate the global withdrawal strategy of the lower limb expressed by synergy analysis.MethodsSixteen healthy subjects received electrical stimulation in the arch of the foot at 2 × RTh intensity assessed at the biceps femoris muscle, to elicit the NWR at three time points: before, during and after immersion of the hand in cold water at 2.6 ± 0.4° (cold pressor test, CPT) to trigger CPM. Electromyographic signals (EMG) were recorded from 2 distal muscles (tibialis anterior, soleus) and 2 proximal muscles (biceps femoris, rectus femoris). Muscle synergies were identified by a non-negative matrix factorization algorithm for the EMG envelope in the 60–180 ms post-stimulus interval. Data were analyzed by a point-by-point Wilcoxon test using a permutation strategy.ResultsThe overall withdrawal pattern was explained by two main synergies (Syn1 and Syn2). Syn1 mainly contributes to EMG of distal muscles, whereas Syn2 contributes to EMG of proximal muscles. During CPT, the magnitude of Syn2 was reduced in the 160–180ms post-stimulus interval (p < 0.05), whereas no changes were found for Syn1.ConclusionsAt least two synergies are required to explain the NWR. Furthermore, results suggest that CPM might differentially affect proximal and distal muscles. Further analysis is needed to provide additional information about the behavior of the individual muscles.

The milestone effect of DNIC in our understanding of pain

2018 ◽  
Author(s):  
Serge Marchand
Keyword(s):  
Inhibitory Control ◽  
Pain Modulation ◽  
The Other ◽  
Major Influence ◽  
Conditioned Pain Modulation ◽  
Pain Mechanisms ◽  
Diffuse Noxious Inhibitory Control ◽  
Endogenous Pain Modulation

While thousands of articles are published each year on pain, only a few have such a major impact on the understanding of pain mechanisms as the landmark paper discussed in this chapter; published by Le Bars and colleagues in 1979, it introduced the concept of diffuse noxious inhibitory control (DNIC; also called diffuse noxious inhibition) mechanisms. Although this work is more than three decades old, it still has a major influence on both the understanding of pain mechanisms and the development of clinical approaches. It is known that apparently similar pain may be caused by different mechanisms: one may be caused by amplified excitatory mechanisms while the other may be related to a deficit of endogenous pain modulation, such as DNIC or conditioned pain modulation (or CPM); these will not respond to the same treatment. The work by Le Bars and colleagues provided a new understanding of mechanisms underlying pain.

scholarly journals Painful Cutaneous Electrical Stimulation vs. Heat Pain as Test Stimuli in Conditioned Pain Modulation

2020 ◽  
Vol 10 (10) ◽  
pp. 684
Author(s):  
Elena Enax-Krumova ◽  
Ann-Christin Plaga ◽  
Kimberly Schmidt ◽  
Özüm S. Özgül ◽  
Lynn B. Eitner ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Test Stimulus ◽  
Evoked Potentials ◽  
Pain Intensity ◽  
Rating Scale ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Heat Pain ◽  
Dominant Hand ◽  
Group Level

Different paradigms can assess the effect of conditioned pain modulation (CPM). The aim of the present study was to compare heat pain, as an often used test stimulus (TS), to painful cutaneous electrical stimulation (PCES), having the advantage of the additional recording of PCES-related evoked potentials. In 28 healthy subjects we applied heat and PCES at the dominant hand as test stimulus (TS) to compare the CPM-effect elicited by hand immersion into cold water (10 °C) as conditioning stimulus (CS). Subjects rated the pain intensity of TS at baseline, during and 5 min after CS application and additionally of CS, on a numerical rating scale (NRS) (0–100). The ‘early’ (during CS–before CS) and ‘late’ (after CS–before CS) CPM-effects were analyzed. Parallel to the PCES, the related evoked potentials were recorded via Cz to evaluate any changes in PCES-amplitudes. CS reduced significantly the pain intensity of both PCES and heat pain as TS. On a group level, the CPM-effect did not differ significantly between both paradigms. Both early and late CPM-effect based on PCES correlated significantly with the CS pain intensity (r = −0.630 and −0.503, respectively), whereas using heat pain the correlation was not significant. We found a significant reduction of PCES-amplitudes during CS, but this did not correlate with the PCES-induced pain intensity. Correlation with the CS painfulness (r = −0.464) did not achieve the significance level after Bonferroni correction. The extent of the CPM effects was similar in both testing paradigms at group level, despite intraindividual differences. Future studies should further elicit the exact mechanisms explaining the modality of these specific differences.

Local hyperalgesia, normal endogenous modulation with pain report beyond its origin: a pilot study prompting further exploration into plantar fasciopathy

2020 ◽  
Vol 20 (2) ◽  
pp. 375-385
Author(s):  
Henrik Riel ◽  
Melanie L. Plinsinga ◽  
Rebecca Mellor ◽  
Shellie A. Boudreau ◽  
Viana Vuvan ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Pain Threshold ◽  
Pressure Pain Threshold ◽  
Plantar Fascia ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Pain Processing ◽  
Pain Thresholds ◽  
Pressure Pain ◽  
Plantar Fasciopathy

AbstractBackground and aimsPersistent tendinopathies were previously considered solely as peripheral conditions affecting the local tendinous tissue until quantitative sensory testing identified involvement of altered pain processing. In similar fashion, pain in patients with persistent plantar fasciopathy may also involve more than local tissue. The aim of this pilot study was to investigate potential differences in conditioned pain modulation and pressure and thermal pain thresholds, between individuals with PF and healthy pain-free controls, as a precursor to a larger-scale study.MethodsWe assessed 16 individuals with plantar fasciopathy and 11 pain-free controls. Plantar fasciopathy diagnosis was: palpation pain of the medial calcaneal tubercle or the proximal plantar fascia, duration ≥3 months, pain intensity ≥2/10, and ultrasound-measured plantar fascia thickness ≥4 mm. Quantitative sensory tests were performed locally at the plantar heel and remotely on the ipsilateral elbow. Assessments included pain thresholds for pressure, heat and cold, and conditioned pain modulation measured as change in local resting pressure pain threshold with cold water hand immersion. Participants rated pain intensity at pain threshold. Additionally, the area and distribution of plantar fasciopathy pain was drawn on a digital body chart of the lower limbs. Descriptive analyses were performed and between-group differences/effects expressed as standardised mean differences (d).ResultsThere was no conditioned pain modulation difference between participants with plantar fasciopathy and controls (d = 0.1). Largest effects were on local pressure pain threshold and reported pain intensity on pressure pain threshold (d > 1.8) followed by pain intensity for heat and cold pain thresholds (d = 0.3–1.5). According to the digital body chart, pain area extended beyond the plantar heel.ConclusionsThe unlikelihood of a difference in conditioned pain modulation yet a pain area extending beyond the plantar heel provide a basis for exploring altered pain processing in a larger-scale study.ImplicationsThis was the first study to investigate the presence of altered pain processing in individuals with plantar fasciopathy using a conditioned pain modulation paradigm and thermal pain thresholds. We found no indication of an altered pain processing based on these measures, however, patients rated pain higher on thresholds compared to controls which may be important to clinical practice and warrants further exploration in the future.

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