Trial reportAnesthesiology2016
Disambiguating Pharmacodynamic Efficacy from Behavior with Neuroimaging: Implications for Analgesic Drug Development.
Trial report in Anesthesiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Pooled it
- Human surrogate models of central sensitization: A critical review and practical guide.European journal of pain (London, England) · 2021Pooled it
- Neuronally-enriched exosomal microRNA-27b mediates acute effects of ibuprofen on reward-related brain activity in healthy adults: a randomized, placebo-controlled, double-blind trial.Scientific reports · 2022Trial
- Impact of ibuprofen and peroxisome proliferator-activated receptor gamma on emotion-related neural activation: A randomized, placebo-controlled trial.Brain, behavior, and immunity · 2021Trial
- Effect of Ibuprofen on BrainAGE: A Randomized, Placebo-Controlled, Dose-Response Exploratory Study.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2018Trial
- Correlation of Pain Reduction with fMRI BOLD Response in Osteoarthritis Patients Treated with Paracetamol: Randomized, Double-Blind, Crossover Clinical Efficacy Study.Pain medicine (Malden, Mass.) · 2018Trial
- A review of descending pain modulation in humans.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- Neural correlates underlying high-frequency stimulation-induced secondary hyperalgesia in humans.Pain reports · 2025Article
- Cortical Dynamics and Postoperative Cognition: Reply.Anesthesiology · 2024Article
- The Role of fMRI in Drug Development: An Update.Advances in neurobiology · 2023Article
- Precision Medicine in Neuropathic Pain.Handbook of experimental pharmacology · 2023Article
- Effects of GABAA receptors in nucleus cuneiformis on the cannabinoid antinociception using the formalin test.Psychopharmacology · 2021Article
- Challenges and opportunities in translational pain research - An opinion paper of the working group on translational pain research of the European pain federation (EFIC).European journal of pain (London, England) · 2021Article
- Current Understanding of the Involvement of the Insular Cortex in Neuropathic Pain: A Narrative Review.International journal of molecular sciences · 2021Review
- Brain Imaging Biomarkers for Chronic Pain.Frontiers in neurology · 2021Review
- Supraspinal Mechanisms Underlying Ocular Pain.Frontiers in medicine · 2021Review
- Behavioral, Physiological and EEG Activities Associated with Conditioned Fear as Sensors for Fear and Anxiety.Sensors (Basel, Switzerland) · 2020Review
- Microglia: sculptors of neuropathic pain?Royal Society open science · 2020Review
- Review
- Objective Pain Assessment: a Key for the Management of Chronic Pain.F1000Research · 2020Review
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 1 institution in 4 countries.
Funding
Abstract
backgroundAttrition rates of new analgesics during drug development are high; poor assay sensitivity with reliance on subjective outcome measures being a crucial factor.
methodsThe authors assessed the utility of functional magnetic resonance imaging with capsaicin-induced central sensitization, a mechanism relevant in neuropathic pain, for obtaining mechanism-based objective outcome measures that can differentiate an effective analgesic (gabapentin) from an ineffective analgesic (ibuprofen) and both from placebo. The authors used a double-blind, randomized phase I study design (N = 24) with single oral doses.
resultsOnly gabapentin suppressed the secondary mechanical hyperalgesia-evoked neural response in a region of the brainstem's descending pain modulatory system (right nucleus cuneiformis) and left (contralateral) posterior insular cortex and secondary somatosensory cortex. Similarly, only gabapentin suppressed the resting-state functional connectivity during central sensitization between the thalamus and secondary somatosensory cortex, which was plasma gabapentin level dependent. A power analysis showed that with 12 data sets, when using neural activity from the left posterior insula and right nucleus cuneiformis, a statistically significant difference between placebo and gabapentin was detected with probability ≥ 0.8. When using subjective pain ratings, this reduced to less than or equal to 0.6.
conclusionsFunctional imaging with central sensitization can be used as a sensitive mechanism-based assay to guide go/no-go decisions on selecting analgesics effective in neuropathic pain in early human drug development. We also show analgesic modulation of neural activity by using resting-state functional connectivity, a less challenging paradigm that is ideally suited for patient studies because it requires no task or pain provocation.
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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.