The effects of gabapentin in human experimental pain models

2010 ◽  
Vol 1 (3) ◽  
pp. 143-148 ◽  
Author(s):  
Thomas P. Enggaard ◽  
Søren S. Mikkelsen ◽  
Stine T. Zwisler ◽  
Niels A. Klitgaard ◽  
Søren H. Sindrup

AbstractBackgroundThe antidepressant drugs imipramine and venlafaxine relieve clinical neuropathic pain and have been shown to increase pain thresholds in healthy volunteers during repetitive electrical sural nerve stimulation causing temporal pain summation, whereas pain during the cold pressor test is unaltered by these drugs. If this pattern of effect in experimental pain models reflects potential efficacy in clinical neuropathic pain, the pain summation model may potentially be used to identify new drugs for such pain conditions. Gabapentinoids are evidence-based treatments of clinical neuropathic pain and could contribute with additional knowledge of the usefulness of the pain summation model.The aim of this studyTo test the analgesic effect of the gabapentinoid gabapentin in a sural nerve stimulation pain model including temporal pain summation and the cold pressor test.Method18 healthy volunteers completed a randomized, double-blind, cross-over trial with medication of 600 mg gabapentin orally dosed 3 times over 24 h against placebo. Pain tests were performed before and 24 h after medication including pain detection and tolerance to single sural nerve stimulation and pain summation threshold to repetitive stimulation (3 Hz). Peak pain intensity and discomfort were rated during a cold pressor test.ResultsCompared to placebo, gabapentin had a highly significant effect on the threshold of pain summation to repetitive electrical sural nerve stimulation (P = 0.009). Gabapentin significantly increased the pain tolerance threshold to single electrical sural nerve stimulation (P = 0.04), whereas the pain detection threshold to single electrical sural nerve stimulation tended to be increased (P = 0.06). No significant differences were found on pain ratings during the cold pressor test.ConclusionGabapentin had a selective hypoalgesic effect in a human experimental pain model of temporal pain summation and the results lend further support to the usefulness of the pain summation model to identify drugs for neuropathic pain.

2000 ◽  
Vol 5 (2) ◽  
pp. 135-140 ◽  
Author(s):  
Lars Arendt-Nielsen ◽  
Poul Pedersen ◽  
Lars Poulsen ◽  
Ole Kæseler Andersen ◽  
Peter Bjerring ◽  
...  

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.


2012 ◽  
Vol 3 (3) ◽  
pp. 116-123 ◽  
Author(s):  
Lise Gormsen ◽  
Flemming W. Bach ◽  
Raben Rosenberg ◽  
Troels S. Jensen

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.


2016 ◽  
Vol 14 (4) ◽  
Author(s):  
Marcelo Coertjens

Introdução: A crioterapia é um recurso que diminui a temperatura corporal local com finalidades terapêuticas. Uma importante repercussão é a vasoconstrição local, que seria o desencadeador de um possível aumento na pressão arterial (PA). Entretanto, não existem trabalhos que comprovem essa suposição. Nossa hipótese é que os resultados das pesquisas de Cold Pressor Test (CPT) avaliando PA acabaram historicamente fundamentando as precauções da crioterapia em relação a pacientes hipertensos. Objetivo: Realizar uma revisão de literatura a respeito das pesquisas que sustentam a precaução da crioterapia em indivíduos hipertensos e verificar sua relação com estudos que utilizaram o CPT. Material e métodos: Trata-se de uma revisão de literatura que utilizou as bases de dados online Medline, Scielo, Lilacs e Google Acadêmico para a realização da pesquisa. Resultado: Apesar de não serem unânimes, diversas pesquisas que utilizaram o CPT encontraram significativos aumentos da atividade nervosa simpática muscular e da PA em normotensos e hipertensos, entretanto não encontramos estudos que tenham comprovado respostas significativas de PA com o uso da crioterapia, principalmente, em hipertensos. Conclusão: Não existem evidências científicas que comprovem a precaução da crioterapia em indivíduos hipertensos. Além disso, os estudos com CPT não são unânimes em relação aos aumentos pressóricos em indivíduos normotensos e hipertensos.Palavras-chave: crioterapia, hemodinâmica, hipertensão, pressão arterial. 


Author(s):  
Guillaume Lamotte ◽  
Christopher J. Boes ◽  
Phillip A. Low ◽  
Elizabeth A. Coon

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Morten Pallisgaard Støve ◽  
Rogerio Pessoto Hirata ◽  
Thorvaldur Skuli Palsson

Abstract Objectives The effect of stretching on joint range of motion is well documented, and although sensory perception has significance for changes in the tolerance to stretch following stretching the underlining mechanisms responsible for these changes is insufficiently understood. The aim of this study was to examine the influence of endogenous pain inhibitory mechanisms on stretch tolerance and to investigate the relationship between range of motion and changes in pain sensitivity. Methods Nineteen healthy males participated in this randomized, repeated-measures crossover study, conducted on 2 separate days. Knee extension range of motion, passive resistive torque, and pressure pain thresholds were recorded before, after, and 10 min after each of four experimental conditions; (i) Exercise-induced hypoalgesia, (ii) two bouts of static stretching, (iii) resting, and (iv) a remote, painful stimulus induced by the cold pressor test. Results Exercise-induced hypoalgesia and cold pressor test caused an increase in range of motion (p<0.034) and pressure pain thresholds (p<0.027). Moderate correlations in pressure pain thresholds were found between exercise-induced hypoalgesia and static stretch (Rho>0.507, p=0.01) and exercise-induced hypoalgesia and the cold pressor test (Rho=0.562, p=0.01). A weak correlation in pressure pain thresholds and changes in range of motion were found following the cold pressor test (Rho=0.460, p=0.047). However, a potential carryover hypoalgesic effect may have affected the results of the static stretch. Conclusions These results suggest that stretch tolerance may be linked with endogenous modulation of pain. Present results suggest, that stretch tolerance may merely be a marker for pain sensitivity which may have clinical significance given that stretching is often prescribed in the rehabilitation of different musculoskeletal pain conditions where reduced endogenous pain inhibition is frequently seen.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kilin Shi ◽  
Tobias Steigleder ◽  
Sven Schellenberger ◽  
Fabian Michler ◽  
Anke Malessa ◽  
...  

AbstractContactless measurement of heart rate variability (HRV), which reflects changes of the autonomic nervous system (ANS) and provides crucial information on the health status of a person, would provide great benefits for both patients and doctors during prevention and aftercare. However, gold standard devices to record the HRV, such as the electrocardiograph, have the common disadvantage that they need permanent skin contact with the patient. Being connected to a monitoring device by cable reduces the mobility, comfort, and compliance by patients. Here, we present a contactless approach using a 24 GHz Six-Port-based radar system and an LSTM network for radar heart sound segmentation. The best scores are obtained using a two-layer bidirectional LSTM architecture. To verify the performance of the proposed system not only in a static measurement scenario but also during a dynamic change of HRV parameters, a stimulation of the ANS through a cold pressor test is integrated in the study design. A total of 638 minutes of data is gathered from 25 test subjects and is analysed extensively. High F-scores of over 95% are achieved for heartbeat detection. HRV indices such as HF norm are extracted with relative errors around 5%. Our proposed approach is capable to perform contactless and convenient HRV monitoring and is therefore suitable for long-term recordings in clinical environments and home-care scenarios.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Andreas M. Weng ◽  
Herbert Köstler ◽  
Thorsten A. Bley ◽  
Christian O. Ritter

Abstract Background The effect of smoking on coronary vasomotion has been investigated in the past with various imaging techniques in both short- and long-term smokers. Additionally, coronary vasomotion has been shown to be normalized in long-term smokers by L-Arginine acting as a substrate for NO synthase, revealing the coronary endothelium as the major site of abnormal vasomotor response. Aim of the prospective cohort study was to investigate coronary vasomotion of young healthy short-term smokers via magnetic resonance cold pressor test with and without the administration of L-Arginine and compare obtained results with the ones from nonsmokers. Methods Myocardial blood flow (MBF) was quantified with first-pass perfusion MRI on a 1.5 T scanner in healthy short-term smokers (N = 10, age: 25.0 ± 2.8 years, 5.0 ± 2.9 pack years) and nonsmokers (N = 10, age: 34.3 ± 13.6) both at rest and during cold pressor test (CPT). Smokers underwent an additional examination after administration of L-Arginine within a median of 7 days of the naïve examination. Results MBF at rest turned out to be 0.77 ± 0.30 (smokers with no L-Arginine; mean ± standard deviation), 0.66 ± 0.21 (smokers L-Arginine) and 0.84 ± 0.08 (nonsmokers). Values under CPT were 1.21 ± 0.42 (smokers no L-Arginine), 1.09 ± 0.35 (smokers L-Arginine) and 1.63 ± 0.33 (nonsmokers). In all groups, MBF was significantly increased under CPT compared to the corresponding rest examination (p < 0.05 in all cases). Additionally, MBF under CPT was significantly different between the smokers and the nonsmokers (p = 0.002). MBF at rest was significantly different between the smokers when L-Arginine was given and the nonsmokers (p = 0.035). Conclusion Short-term smokers showed a reduced response to cold both with and without the administration of L-Arginine. However, absolute MBF values under CPT were lower compared to nonsmokers independently of L-Arginine administration.


1985 ◽  
Vol 69 (5) ◽  
pp. 533-540 ◽  
Author(s):  
Gianfranco Parati ◽  
Guido Pomidossi ◽  
Agustin Ramirez ◽  
Bruno Cesana ◽  
Giuseppe Mancia

1. In man evaluation of neural cardiovascular regulation makes use of a variety of tests which address the excitatory and reflex inhibitory neural influences that control circulation. Because interpretation of these tests is largely based on the magnitude of the elicited haemodynamic responses, their reproducibility in any given subject is critical. 2. In 39 subjects with continuous blood pressure (intra-arterial catheter) and heart rate monitoring we measured (i) the blood pressure and heart rate rises during hand-grip and cold-pressor test, (ii) the heart rate changes occurring during baroreceptor stimulation and deactivation by injection of phenylephrine and trinitroglycerine, and (iii) the heart rate and blood pressure changes occurring with alteration in carotid baroreceptor activity by a neck chamber. Each test was carefully standardized and performed at 30 min intervals for a total of six times in each subject. 3. The results showed that the responses to any test were clearly different from one another and that this occurred in all subjects studied. For the group as a whole the average response variability (coefficient of variation) ranged from 10.2% for the blood pressure response to carotid baroreceptor stimulation to 44.2% for the heart rate response to cold-pressor test. The variability of the responses was not related to basal blood pressure or heart rate, nor to the temporal sequence of the test performance. 4. Thus tests employed for studying neural cardiovascular control in man produce responses whose reproducibility is limited. This phenomenon may make it more difficult to define the response magnitude typical of each subject, as well as its comparison in different conditions and diseases.


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