Trial reportPloS one2013
Evaluation of anti-hyperalgesic and analgesic effects of two benzodiazepines in human experimental pain: a randomized placebo-controlled study.
Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01011036 (Effects of Gaba-a-Agonists on Pain Mechanisms), which is not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effects of Gaba-a-Agonists on Pain Mechanisms: An Experimental Study in Healthy Volunteers
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Human surrogate models of central sensitization: A critical review and practical guide.European journal of pain (London, England) · 2021Pooled it
- The α2-Subunit Preferring GABA Positive Allosteric Modulator, N-Desmethyl-Clobazam in Peripheral Neuropathic Pain Patients: Results of a Phase IIa Randomised Placebo-Controlled Ascending Dose Study.European journal of pain (London, England) · 2026Trial
- Analgesic potential of PF-06372865, an α2/α3/α5 subtype-selective GABABritish journal of anaesthesia · 2019Trial
- The use of a battery of pain models to detect analgesic properties of compounds: a two-part four-way crossover study.British journal of clinical pharmacology · 2017Trial
- Single dose delta-9-tetrahydrocannabinol in chronic pancreatitis patients: analgesic efficacy, pharmacokinetics and tolerability.British journal of clinical pharmacology · 2016Trial
- Electrical Evoked Potentials After Perioperative Pain Neuroscience Education or Back School Education: A Subgroup Analysis of a Randomized Controlled Trial.Journal of clinical medicine · 2026Article
- Ice water immersion does not activate diffuse noxious inhibitory controls of spinal reflexes in sedated or anaesthetised dogs (Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Observational evidence linking psychotropic medicines to the dispensing of opioid agents in later life.Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society · 2024Observational
- Central Sensitization and Pain: Pathophysiologic and Clinical Insights.Current neuropharmacology · 2024Article
- Pressure Pain Thresholds and Central Sensitization in Relation to Psychosocial Predictors of Chronicity in Low Back Pain.Diagnostics (Basel, Switzerland) · 2023Article
- Risks of complicated acute appendicitis in patients with psychiatric disorders.BMC psychiatry · 2022Article
- GABAkines - Advances in the discovery, development, and commercialization of positive allosteric modulators of GABAPharmacology & therapeutics · 2022Review
- 5-International journal of molecular sciences · 2021Article
- Endogenous Pain Modulation Profiles Among Individuals With Chronic Pain: Relation to Opioid Use.The journal of pain · 2019Article
- Cortical mapping of painful electrical stimulation by quantitative electroencephalography: unraveling the time-frequency-channel domain.Journal of pain research · 2017Article
- A literature review on the pharmacological sensitivity of human evoked hyperalgesia pain models.British journal of clinical pharmacology · 2016Review
- The clobazam metabolite N-desmethyl clobazam is an α2 preferring benzodiazepine with an improved therapeutic window for antihyperalgesia.Neuropharmacology · 2016Article
- Analgesia and unwanted benzodiazepine effects in point-mutated mice expressing only one benzodiazepine-sensitive GABAA receptor subtype.Nature communications · 2015Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsCompounds that act on GABA-receptors produce anti-hyperalgesia in animal models, but little is known on their effects in humans. The aim of this study was to explore the potential usefulness of GABA-agonism for the control of pain in humans. Two agonists at the benzodiazepine-binding site of GABAA-receptors (clobazam and clonazepam) were studied using multiple experimental pain tests. Positive results would support further investigation of GABA agonism for the control of clinical pain.
methodsIn a randomized double-blind crossover design, 16 healthy male volunteers received clobazam 20 mg, clonazepam 1 mg and tolterodine 1 mg (active placebo). The area of static hyperalgesia after intradermal capsaicin injection was the primary endpoint. Secondary endpoints were: area of dynamic hyperalgesia, response to von Frey hair stimulation, pressure pain thresholds, conditioned pain modulation, cutaneous and intramuscular electrical pain thresholds (1, 5 and 20 repeated stimulation), and pain during cuff algometry.
resultsFor the primary endpoint, an increase in the area of static hyperalgesia was observed after administration of placebo (p<0.001), but not after clobazam and clonazepam. Results suggestive for an anti-hyperalgesic effect of the benzodiazepines were obtained with all three intramuscular pain models and with cuff algometry. No effect could be detected with the other pain models employed.
conclusionsCollectively, the results are suggestive for a possible anti-hyperalgesic effect of drugs acting at the GABAA-receptors in humans, particularly in models of secondary hyperalgesia and deep pain. The findings are not conclusive, but support further clinical research on pain modulation by GABAergic drugs. Because of the partial results, future research should focus on compounds acting selectively on subunits of the GABA complex, which may allow the achievement of higher receptor occupancy than unselective drugs. Our data also provide information on the most suitable experimental models for future investigation of GABAergic compounds.
trial registrationClinicalTrials.gov NCT01011036.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.