scholarly journals Pregabalin Has Analgesic, Ventilatory, and Cognitive Effects in Combination with Remifentanil

2016 ◽  
Vol 124 (1) ◽  
pp. 141-149 ◽  
Author(s):  
Marianne Myhre ◽  
Lien My Diep ◽  
Audun Stubhaug
Keyword(s):  
Pain Score ◽  
Cold Pressor Test ◽  
Experimental Pain ◽  
Cold Pressor ◽  
Analgesic Effects ◽  
Rapid Information Processing ◽  
End Tidal ◽  
Double Blinded ◽  
Dose Dependent ◽  
Higher Doses

Abstract Background Pregabalin is widely used perioperatively. The authors explored the effects of pregabalin, remifentanil, and their combination on experimental pain, ventilatory, and cognitive function. Methods In a randomized, double-blinded crossover study, 12 volunteers received (1) pregabalin + placebo, (2) placebo + remifentanil, (3) pregabalin + remifentanil, and (4) placebo + placebo. Pregabalin 150 mg/placebo was administered twice orally. After baseline, remifentanil/placebo was given as effect-site target-controlled infusion (TCI): 0.6, 1.2, and 2.4 ng/ml. Pain during cold pressor test was scored on visual analog scale (0 to 100 mm). Ventilation was measured by spirometry and cognition tested with Color-Word Interference and Rapid Information Processing tests. Results Pain intensity after placebo was (mean) 72 mm (95% CI, 62 to 83). Pregabalin reduced pain score by −10 mm (−14 to −7, P < 0.001). Remifentanil had dose-dependent analgesic effect, reducing pain score by −47 mm (−54 to −39, P < 0.001) on highest TCI level, whereas pregabalin + remifentanil exerted additive effect, reducing pain score by −57 mm (−64 to −50, P < 0.001). Respiratory depression was potentiated by adding pregabalin to remifentanil; end-tidal carbon dioxide was 39.3 mmHg (37.2 to 41.3) with placebo, increased 1.8 mmHg (−0.9 to 4.6, P = 0.4) with pregabalin, 10.1 mmHg (4.9 to 15.4, P < 0.001) with remifentanil, and 16.4 mmHg (11.3 to 21.5, P < 0.001) with pregabalin + remifentanil on highest TCI level. The combination pregabalin + remifentanil, but not either drug alone, adversely affected all cognitive tests. Conclusions The combination of pregabalin and remifentanil had additive analgesic effects, pregabalin potentiated remifentanil ventilatory depression, and the combination adversely affected cognition. These results question the clinical benefit of the combination compared with higher doses of opioids.

scholarly journals Dose-dependent Effects of Smoked Cannabis on Capsaicin-induced Pain and Hyperalgesia in Healthy Volunteers

2007 ◽  
Vol 107 (5) ◽  
pp. 785-796 ◽  
Author(s):  
Mark Wallace ◽  
Gery Schulteis ◽  
J Hampton Atkinson ◽  
Tanya Wolfson ◽  
Deborah Lazzaretto ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Drug Exposure ◽  
Pain Perception ◽  
Experimental Pain ◽  
High Dose ◽  
Significant Difference ◽  
Pain State ◽  
Double Blinded ◽  
Dose Dependent ◽  
Higher Doses

Background Although the preclinical literature suggests that cannabinoids produce antinociception and antihyperalgesic effects, efficacy in the human pain state remains unclear. Using a human experimental pain model, the authors hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced by intradermal capsaicin. Methods In a randomized, double-blinded, placebo-controlled, crossover trial in 15 healthy volunteers, the authors evaluated concentration-response effects of low-, medium-, and high-dose smoked cannabis (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannabinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 min after drug exposure, and pain, hyperalgesia, tetrahydrocannabinol plasma levels, and side effects were assessed. Results Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 min after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose, nor was there an effect on the area of hyperalgesia at any dose. Significant negative correlations between pain perception and plasma delta-9-tetrahydrocannabinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests. Conclusions This study suggests that there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain.

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 < 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

Behavioral and Physiological Effects of Remifentanil and Alfentanil in Healthy Volunteers 

1999 ◽  
Vol 90 (3) ◽  
pp. 718-726 ◽  
Author(s):  
Matthew L. Black ◽  
Joanna L. Hill ◽  
James P. Zacny
Keyword(s):  
Healthy Volunteers ◽  
Dose Range ◽  
Subjective Effects ◽  
Cold Pressor Test ◽  
Drug Effects ◽  
Cold Pressor ◽  
Psychomotor Tests ◽  
Potency Ratio ◽  
Psychomotor Effects ◽  
Double Blinded

Background The subjective and psychomotor effects of remifentanil have not been evaluated. Accordingly, the authors used mood inventories and psychomotor tests to characterize the effects of remifentanil in healthy, non-drug-abusing volunteers. Alfentanil was used as a comparator drug. Methods Ten healthy volunteers were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial in which they received an infusion of saline, remifentanil, or alfentanil for 120 min. The age- and weight-adjusted infusions (determined with STANPUMP, a computer modeling software package) were given to achieve three predicted constant plasma levels for 40 min each of remifentanil (0.75, 1.5, and 3 ng/ml) and alfentanil (16, 32, and 64 ng/ml). Mood forms and psychomotor tests were completed, and miosis was assessed, during and after the infusions. In addition, analgesia was tested at each dose level using a cold-pressor test. Results Remifentanil had prototypic micro-like opioid subjective effects, impaired psychomotor performance, and produced analgesia. Alfentanil at the dose range tested had more mild effects on these measures, and the analgesia data indicated that a 40:1 potency ratio, rather than the 20:1 ratio we used, may exist between remifentanil and alfentanil. A psychomotor test administered 60 min after the remifentanil infusion was discontinued showed that the volunteers were still impaired, although they reported feeling no drug effects. Conclusions The notion that the pharmacodynamic effects of remifentanil are extremely short-lived after the drug is no longer administered must be questioned given our findings that psychomotor effects were still apparent 1 h after the infusion was discontinued.

scholarly journals Classification of Game Demand and the Presence of Experimental Pain Using Functional Near-Infrared Spectroscopy

2021 ◽  
Vol 2 ◽  
Author(s):  
Stephen H. Fairclough ◽  
Chelsea Dobbins ◽  
Kellyann Stamp
Keyword(s):  
Infrared Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Cold Pressor Test ◽  
Experimental Pain ◽  
Cold Pressor ◽  
Pain Tolerance ◽  
Support Vector ◽  
Test Protocol ◽  
Functional Near Infrared Spectroscopy

Pain tolerance can be increased by the introduction of an active distraction, such as a computer game. This effect has been found to be moderated by game demand, i.e., increased game demand = higher pain tolerance. A study was performed to classify the level of game demand and the presence of pain using implicit measures from functional Near-InfraRed Spectroscopy (fNIRS) and heart rate features from an electrocardiogram (ECG). Twenty participants played a racing game that was configured to induce low (Easy) or high (Hard) levels of demand. Both Easy and Hard levels of game demand were played with or without the presence of experimental pain using the cold pressor test protocol. Eight channels of fNIRS data were recorded from a montage of frontal and central-parietal sites located on the midline. Features were generated from these data, a subset of which were selected for classification using the RELIEFF method. Classifiers for game demand (Easy vs. Hard) and pain (pain vs. no-pain) were developed using five methods: Support Vector Machine (SVM), k-Nearest Neighbour (kNN), Naive Bayes (NB) and Random Forest (RF). These models were validated using a ten fold cross-validation procedure. The SVM approach using features derived from fNIRS was the only method that classified game demand at higher than chance levels (accuracy = 0.66, F1 = 0.68). It was not possible to classify pain vs. no-pain at higher than chance level. The results demonstrate the viability of utilising fNIRS data to classify levels of game demand and the difficulty of classifying pain when another task is present.

scholarly journals Muscle stretching – the potential role of endogenous pain inhibitory modulation on stretch tolerance

2019 ◽  
Vol 19 (2) ◽  
pp. 415-422 ◽  
Author(s):  
Morten Pallisgaard Støve ◽  
Rogerio Pessoto Hirata ◽  
Thorvaldur Skuli Palsson
Keyword(s):  
Range Of Motion ◽  
Cold Pressor Test ◽  
Experimental Pain ◽  
Cold Pressor ◽  
Knee Extension ◽  
Painful Stimulus ◽  
Control Group ◽  
Inhibitory System ◽  
Pain Group ◽  
Resistive Torque

Abstract Background and aims The effect of stretching on joint range of motion is well documented and is primarily related to changes in the tolerance to stretch, but the mechanisms underlying this change are still largely unknown. The aim of this study was to investigate the influence of a remote, painful stimulus on stretch tolerance. Methods Thirty-four healthy male subjects were recruited and randomly assigned to an experimental pain group (n=17) or a control group (n=17). Passive knee extension range of motion, the activity of hamstring muscles and passive resistive torque were measured with subjects in a seated position. Three consecutive measures were performed with a 5-min interval between. A static stretch protocol was utilized in both groups to examine the effect of stretching and differences in stretch tolerance between groups. Following this, the pain-group performed a cold pressor test which is known to engage the endogenous pain inhibitory system after which measurements were repeated. Results A significant increase in knee extension range of motion was found in the pain group compared with controls (ANCOVA: p<0.05). No difference was found in muscle activity or passive resistive torque between groups (ANCOVA p>0.091). Conclusions Passive knee extension range of motion following stretching increased when following a distant, painful stimulus, potentially engaging the endogenous pain inhibitory systems. Current findings indicate a link between increased tolerance to stretch and endogenous pain inhibition. Implications The current findings may have implications for clinical practice as they indicate that a distant painful stimulus can influence range of motion in healthy individuals. This implies that the modulation of pain has significance for the efficacy of stretching which is important knowledge when prescribing stretching as part of rehabilitation.

scholarly journals A 5-HT Antagonist (UP 26-91) versus Codeine and Placebo in a Human Experimental Pain Study

2000 ◽  
Vol 5 (2) ◽  
pp. 135-140 ◽  
Author(s):  
Lars Arendt-Nielsen ◽  
Poul Pedersen ◽  
Lars Poulsen ◽  
Ole Kæseler Andersen ◽  
Peter Bjerring ◽  
...  
Keyword(s):  
Serotonin Receptor ◽  
Pain Threshold ◽  
Statistical Significance ◽  
Cold Pressor Test ◽  
Experimental Pain ◽  
Cold Pressor ◽  
Double Blind ◽  
Stimulus Response ◽  
Pressor Test ◽  
Pain Models

BACKGROUND: This double-blind, randomized, crossover study compared the potential analgesic effect of the serotonin receptor antagonist UP 26-91 (50 mg, 150 mg and 300 mg) with that of codeine (100 mg) and placebo by use of different human experimental pain models.SUBJECTS AND METHODS: In experiment 1, pain detection and tolerance thresholds to heat, pressure and pain ratings during the cold pressor test were measured. In experiment 2, the pain threshold to single and repetitive (temporal summation) electrical sural nerve stimulation, and the pain intensity on a visual analogue scale to supra pain threshold electrical stimulation (stimulus-response-function) were measured. Tests were performed before, and 1, 2 and 6 h after drug administration.RESULTS: UP 26-91 did not show a marked effect on the experimental pain tests. Most of the variables tended to show a better effect from codeine than from placebo, but statistical significance for peak pain was only reached during the cold pressor test (P=0.011).CONCLUSIONS: In the present doses, the serotonin antagonist UP 26-91 had no effect on the experimental pain models applied.

scholarly journals Immune Biomarker Response Depends on Choice of Experimental Pain Stimulus in Healthy Adults: A Preliminary Study

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Yenisel Cruz-Almeida ◽  
Christopher D. King ◽  
Shannon M. Wallet ◽  
Joseph L. Riley
Keyword(s):  
Cold Pressor Test ◽  
Experimental Pain ◽  
Cold Pressor ◽  
Painful Stimulus ◽  
Pain Stimulus ◽  
Biomarker Response ◽  
Pain Ratings ◽  
Multiple Biomarkers ◽  
Chronic Pain Conditions ◽  
Pain Stimuli

Few studies in healthy subjects have examined the neuroimmune responses associated with specific experimental pain stimuli, while none has measured multiple biomarkers simultaneously. The aim of the present study was to compare the neuro-immune responses following two common experimental pain stimuli: cold pressor test (CPT) and focal heat pain (FHP). Eight adults participated in two counterbalanced experimental sessions of FHP or CPT with continuous pain ratings and blood sampling before and 30 minutes after the sessions. Despite similar pain intensity ratings (FHP = 42.2±15.3; CPT = 44.5±34.1; P=0.871), CPT and FHP induced different neuro-immune biomarker responses. CPT was accompanied by significant increases in cortisol (P=0.046) and anti-inflammatory cytokine IL-10 (P=0.043) with significant decreases in several pro-inflammatory mediators (IL-1β (P=0.028), IL-12 (P=0.012), TNF-α (P=0.039), and MCP-1 (P=0.038)). There were nonsignificant biomarker changes during the FHP session. There were close to significant differences between the sessions for IL-1β (P=0.081), IFN-γ (P=0.072), and IL-12 (P=0.053) with biomarkers decreasing after CPT and increasing after FHP. There were stronger associations between catastrophizing and most biomarkers after CPT compared to FHP. Our results suggest that CPT is a stressful and painful stimulus, while FHP is mostly a painful stimulus. Thus, each experimental pain stimulus can activate different neuro-immune cascades, which are likely relevant for the interpretation of studies in chronic pain conditions.

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