scholarly journals Pleasant Pain Relief and Inhibitory Conditioned Pain Modulation: A Psychophysical Study

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Nathalie Bitar ◽  
Serge Marchand ◽  
Stéphane Potvin
Keyword(s):  
Pain Relief ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Thermal Stimulus ◽  
Analgesic Effects ◽  
Opponent Process ◽  
Before And After ◽  
Opponent Process Theory

Background. Inhibitory conditioned pain modulation (ICPM) is one of the principal endogenous pain inhibition mechanisms and is triggered by strong nociceptive stimuli. Recently, it has been shown that feelings of pleasantness are experienced after the interruption of noxious stimuli. Given that pleasant stimuli have analgesic effects, it is therefore possible that the ICPM effect is explained by the confounding effect of pleasant pain relief. The current study sought to verify this assumption. Methods. Twenty-seven healthy volunteers were recruited. Thermal pain thresholds were measured using a Peltier thermode. ICPM was then measured by administering a tonic thermal stimulus before and after a cold-pressor test (CPT). Following the readministration of the CPT, pleasant pain relief was measured for 4 minutes. According to the opponent process theory, pleasant relief should be elicited following the interruption of a noxious stimulus. Results. The interruption of the CPT induced a mean and peak pleasant pain relief of almost 40% and 70%, respectively. Pleasant pain relief did not correlate with ICPM amplitude but was positively correlated with pain level during the CPT. Finally, a negative correlation was observed between pleasant pain relief and anxiety. Discussion. Results show that the cessation of a strong nociceptive stimulus elicits potent pleasant pain relief. The lack of correlation between ICPM and pleasant pain relief suggests that the ICPM effect, as measured by sequential paradigms, is unlikely to be fully explained by a pleasant pain relief phenomenon.

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.

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.

scholarly journals Comparison of Thermal and Electrical Modalities in the Assessment of Temporal Summation of Pain and Conditioned Pain Modulation

2021 ◽  
Vol 2 ◽  
Author(s):  
Monica Sean ◽  
Alexia Coulombe-Lévêque ◽  
Martine Bordeleau ◽  
Matthieu Vincenot ◽  
Louis Gendron ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Temporal Summation ◽  
Cold Pressor Test ◽  
Conditioning Stimulus ◽  
Cold Pressor ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Electrical Nerve Stimulation ◽  
Clinical Assessments ◽  
Healthy Participants

Temporal summation of pain (TSP) and conditioned pain modulation (CPM) can be measured using a thermode and a cold pressor test (CPT). Unfortunately, these tools are complex, expensive, and are ill-suited for routine clinical assessments. Building on the results from an exploratory study that attempted to use transcutaneous electrical nerve stimulation (TENS) to measure CPM and TSP, the present study assesses whether a “new” TENS protocol can be used instead of the thermode and CPT to measure CPM and TSP. The objective of this study was to compare the thermode/CPT protocol with the new TENS protocol, by (1) measuring the association between the TSP evoked by the two protocols; (2) measuring the association between the CPM evoked by the two protocols; and by (3) assessing whether the two protocols successfully trigger TSP and CPM in a similar number of participants. We assessed TSP and CPM in 50 healthy participants, using our new TENS protocol and a thermode/CPT protocol (repeated measures and randomized order). In the TENS protocol, both the test stimulus (TS) and the conditioning stimulus (CS) were delivered using TENS; in the thermode/CPT protocol, the TS was delivered using a thermode and the CS consisted of a CPT. There was no association between the response evoked by the two protocols, neither for TSP nor for CPM. The number of participants showing TSP [49 with TENS and 29 with thermode (p &lt; 0.001)] and CPM [16 with TENS and 30 with thermode (p = 0.01)] was different in both protocols. Our results suggest that response to one modality does not predict response to the other; as such, TENS cannot be used instead of a thermode/CPT protocol to assess TSP and CPM without significantly affecting the results. Moreover, while at first glance it appears that TENS is more effective than the thermode/CPT protocol to induce TSP, but less so to induce CPM, these results should be interpreted carefully. Indeed, TSP and CPM response appear to be modality-dependent as opposed to an absolute phenomenon, and the two protocols may tap into entirely different mechanisms, especially in the case of TSP.

scholarly journals Reference values of conditioned pain modulation

2019 ◽  
Vol 19 (2) ◽  
pp. 279-286
Author(s):  
Jürg Schliessbach ◽  
Christian Lütolf ◽  
Konrad Streitberger ◽  
Pasquale Scaramozzino ◽  
Lars Arendt-Nielsen ◽  
...  
Keyword(s):  
Reference Values ◽  
Cold Pressor Test ◽  
Conditioning Stimulus ◽  
Cold Pressor ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Abnormal Finding ◽  
Withdrawal Reflex ◽  
Endogenous Pain Modulation ◽  
Electrical Stimuli

Abstract Background and aims Endogenous pain modulation can be studied in humans by conditioned pain modulation (CPM): pain induced by a test stimulus is attenuated by a distantly applied noxious conditioning stimulus. The detection of impaired CPM in individual patients is of potential importance to understand the pathophysiology and predict outcomes. However, it requires the availability of reference values. Methods We determined reference values of CPM in 146 pain-free subjects. Pressure and electrical stimulation were the test stimuli. For electrical stimuli, we recorded both pain threshold and threshold for the nociceptive withdrawal reflex. Cold pressor test was the conditioning stimulus. The 5th, 10th and 25th percentiles for the three tests were computed by quantile regression analyses. Results The average thresholds increased after the conditioning stimulus for all three tests. However, a subset of subjects displayed a decrease in thresholds during the conditioning stimulus. This produced negative values for most of the computed percentiles. Conclusions This study determined percentile reference values of CPM that can be used to better phenotype patients for clinical and research purposes. The negative value of percentiles suggests that a slightly negative CPM effect can be observed in pain-free volunteers. Implications Pain facilitation rather than inhibition during the conditioning stimulus occurs in some pain-free volunteers and may not necessarily represent an abnormal finding.

Effect of conditioned pain modulation on long-term potentiation-like pain amplification in humans

2016 ◽  
Vol 12 (1) ◽  
pp. 124
Author(s):  
Weiwei Xia ◽  
Carsten Dahl Mørch ◽  
Dagfinn Matre ◽  
Ole Kæseler Andersen
Keyword(s):  
Electrical Stimulation ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Long Term Potentiation ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Control Session ◽  
Mechanical Stimuli ◽  
Term Potentiation

AbstractAimThe current study aimed to explore the effect of conditioned pain modulation (CPM) on the long-term potentiation (LTP)-like pain amplification induced by peripheral 10 Hz conditioning electrical stimulation (CES).MethodsSensory changes and neurogenic inflammatory vas-cular reactions induced by 10 Hz CES were assessed in twenty subjects in a randomized crossover design involving two experimental days separated by at least one week. The CPM effect was activated by cold pressor test (CPT) (4 °C) which was applied immediately before the 10 Hz CES in the active session and 32 °C water was used in the control session. Perceptual intensity ratings to single electrical stimulation (SES) at the conditioned skin site and to mechanical stimuli (pinprick and light stroking) in the immediate vicinity of the electrode for CES were recorded. Superficial blood flow (SBF), skin temperature (ST), and heat pain threshold (HPT) were also measured. The pain intensities during the CES process were recorded and the short-form McGill Pain Questionnaire (SF-MPQ) was used for assessing the pain experience.ResultsCPT reduced the pain perception increments to pin-prick (12.8 g) and light stroking stimuli after 10 Hz CES compared to the control session. Moreover, CPT resulted in lower pain intensity ratings during the CES process but without significant changes in the SF-MPQ scores between the two sessions. The SBF and ST were found to increase after CES and then gradually decline but without differences between the CPT and the control sessions. No CPM effect was found for HPT and pain intensity increments to SES.ConclusionsThe cold pressor test inhibited heterotopic perception amplification to mechanical stimuli after conditioning electrical stimulation. The results indicate that endogenous descending inhibitory systems may affect pain-amplificatory mechanisms.

scholarly journals Benefit and Risk Evaluation of Biased μ-Receptor Agonist Oliceridine versus Morphine

2020 ◽  
Vol 133 (3) ◽  
pp. 559-568 ◽  
Author(s):  
Albert Dahan ◽  
C. Jan van Dam ◽  
Marieke Niesters ◽  
Monique van Velzen ◽  
Michael J. Fossler ◽  
...  
Keyword(s):  
Utility Function ◽  
Respiratory Depression ◽  
Receptor Agonist ◽  
Ventilatory Response ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Population Pharmacokinetic ◽  
Potency Ratio ◽  
Analgesic Effects ◽  
Hypercapnic Ventilatory Response

Background To improve understanding of the respiratory behavior of oliceridine, a μ-opioid receptor agonist that selectively engages the G-protein–coupled signaling pathway with reduced activation of the β-arrestin pathway, the authors compared its utility function with that of morphine. It was hypothesized that at equianalgesia, oliceridine will produce less respiratory depression than morphine and that this is reflected in a superior utility. Methods Data from a previous trial that compared the respiratory and analgesic effects of oliceridine and morphine in healthy male volunteers (n = 30) were reanalyzed. A population pharmacokinetic–pharmacodynamic analysis was performed and served as basis for construction of utility functions, which are objective functions of probability of analgesia, P(analgesia), and probability of respiratory depression, P(respiratory depression). The utility function = P(analgesia ≥ 0.5) – P(respiratory depression ≥ 0.25), where analgesia ≥ 0.5 is the increase in hand withdrawal latency in the cold pressor test by at least 50%, and respiratory depression ≥ 0.25 is the decrease of the hypercapnic ventilatory response by at least 25%. Values are median ± standard error of the estimate. Results The two drugs were equianalgesic with similar potency values (oliceridine: 27.9 ± 4.9 ng/ml; morphine 34.3 ± 9.7 ng/ml; potency ratio, 0.81; 95% CI, 0.39 to 1.56). A 50% reduction of the hypercapnic ventilatory response by morphine occurred at an effect-site concentration of 33.7 ± 4.8 ng/ml, while a 25% reduction by oliceridine occurred at 27.4 ± 3.5 ng/ml (potency ratio, 2.48; 95% CI, 1.65 to 3.72; P &lt; 0.01). Over the clinically relevant concentration range of 0 to 35 ng/ml, the oliceridine utility function was positive, indicating that the probability of analgesia exceeds the probability of respiratory depression. In contrast, the morphine function was negative, indicative of a greater probability of respiratory depression than analgesia. Conclusions These data indicate a favorable oliceridine safety profile over morphine when considering analgesia and respiratory depression over the clinical concentration range. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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.

Differential pain modulation in patients with peripheral neuropathic pain and fibromyalgia

2012 ◽  
Vol 3 (3) ◽  
pp. 116-123 ◽  
Author(s):  
Lise Gormsen ◽  
Flemming W. Bach ◽  
Raben Rosenberg ◽  
Troels S. Jensen
Keyword(s):  
Neuropathic Pain ◽  
Cold Water ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Pain Modulation ◽  
Pain Tolerance ◽  
Spontaneous Pain ◽  
Peripheral Neuropathic Pain ◽  
Pressor Test ◽  
Pain Patients

AbstractBackgroundThe definition of neuropathic pain has recently been changed by the International Association for the Study of Pain. This means that conditions such as fibromyalgia cannot, as sometimes discussed, be included in the neuropathic pain conditions. However, fibromyalgia and peripheral neuropathic pain share common clinical features such as spontaneous pain and hypersensitivity to external stimuli. Therefore, it is of interest to directly compare the conditions.Material and methodsIn this study we directly compared the pain modulation in neuropathic pain versus fibromyalgia by recording responses to a cold pressor test in 30 patients with peripheral neuropathic pain, 28 patients with fibromyalgia, and 26 pain-free age-and gender-matched healthy controls. Patients were asked to rate their spontaneous pain on a visual analog scale (VAS (0–100 mm) immediately before and immediately after the cold pressor test. Furthermore the duration (s) of extremity immersion in cold water was used as a measure of the pain tolerance threshold, and the perceived pain intensity at pain tolerance on the VAS was recorded on the extremity in the water after the cold pressor test. In addition, thermal (thermo tester) and mechanical stimuli (pressure algometer) were used to determine sensory detection, pain detection, and pain tolerance thresholds in different body parts. All sensory tests were done by the same examiner, in the same room, and with each subject in a supine position. The sequence of examinations was the following: (1) reaction time, (2) pressure thresholds, (3) thermal thresholds, and (4) cold pressor test. Reaction time was measured to ensure that psychomotoric inhibitions did not influence pain thresholds.ResultsPain modulation induced by a cold pressor test reduced spontaneous pain by 40% on average in neuropathic pain patients, but increased spontaneous pain by 2.6% in fibromyalgia patients. This difference between fibromyalgia and neuropathic pain patients was significant (P < 0.002). Fibromyalgia patients withdrew their extremity from the cold water significantly earlier than neuropathic pain patients and healthy controls; however, they had a higher perceived pain intensity on the VAS than neuropathic pain patients and control subjects. Furthermore, neuropathic pain patients had a localized hypersensitivity to mechanical and thermal stimuli in the affected area of the body. In contrast, fibromyalgia patients displayed a general hypersensitivity to mechanical and thermal stimuli when the stimuli were rated by the VAS, and hypersensitivity to some of the sensory stimuli.ConclusionsThese findings are the first to suggest that a conditioning stimulus evoked by a cold pressor test reduced spontaneous ongoing pain in patients with peripheral neuropathic pain, but not in fibromyalgia patients when directly compared. The current study supports the notion that fibromyalgia and neuropathic pain are distinct pain conditions with separate sensory patterns and dysfunctions in pain-modulating networks. Fibromyalgia should therefore not, as sometimes discussed, be included in NP conditions.ImplicationsOn the basis of the findings, it is of interest to speculate on the underlying mechanisms. The results are consistent with the idea that peripheral neuropathic pain is primarily driven from damaged nerve endings in the periphery, while chronic fibromyalgia pain may be a central disorder with increased activity in pain-facilitating systems.

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