ReviewPain2025
Discordance between preclinical and clinical testing of Na V 1.7-selective inhibitors for pain.
Review in Pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Systematic Review of Stem Cell Secretome-Derived Exosomes for Neuropathic Pain: Therapeutic Mechanisms and Translational Potential.Molecular neurobiology · 2026Pooled it
- Deeper delving Nav1.8 inhibitor Suzetrigine in chronic pain.Acta pharmacologica Sinica · 2026Article
- Antigen-Detected NMR for Minimal Epitope Engineering and Structure-Guided Selection of a NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chasing the Wrong Door for 30 Years: Is Suzetrigine the Key to Selective Pain Relief?Medicina (Kaunas, Lithuania) · 2026Review
- Induced Pluripotent Stem Cell-Based Platforms for Cardiac-Related Pain Research: Molecular Mechanisms, Experimental Models, and Therapeutic Applications.International journal of molecular sciences · 2026Review
- Effects of putative chronic pain models on locomotor activity in female and male mice.The journal of pain · 2026Article
- Review
- Review
- Sodium Channel Inhibitors in Clinical Development for Pain Management: A Focused Review.CNS drugs · 2026Review
- Targeting NaInternational journal of molecular sciences · 2026Review
- Shaping the Action Potential in Dorsal Root and Trigeminal Ganglia Neurons: Relevance to Pain Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Article
- Dorsal Root Ganglion as a Hub for Peripheral Sensitization: A Hierarchical Regulation Model and Translational Progress.Journal of pain research · 2026Review
- Targeting NaBritish journal of anaesthesia · 2025Article
- Voltage-Gated Ion Channels in Neuropathic Pain Signaling.Life (Basel, Switzerland) · 2025Review
- Nav1.8 and Chronic Pain: From Laboratory Animals to Clinical Patients.Biomolecules · 2025Review
- Preclinical Animal Models to Investigate the Role of NaLife (Basel, Switzerland) · 2025Review
- Mimicking opioid analgesia in cortical pain circuits.bioRxiv : the preprint server for biology · 2025Article
- Injury alters sensory, motor, and integrative elements underlying operant conditioning in the medicinal leech.PloS one · 2025Article
- Hyperalgesic Priming in the Transition From Acute to Chronic Pain: Focus on Different Models and the Molecular Mechanisms Involved.Journal of pain research · 2025Review
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.
Funding
Abstract
abstractThe voltage-gated sodium channel Na V 1.7 plays an important role in pain processing according to genetic data. Those data made Na V 1.7 a popular drug target, especially since its relatively selective expression in nociceptors promised pain relief without the adverse effects associated with broader sodium channel blockade. Despite encouraging preclinical data in rodents, Na V 1.7-selective inhibitors have not yet proven effective in clinical trials. Discrepancies between preclinical and clinical results should raise alarms. We reviewed preclinical and clinical reports on the analgesic efficacy of Na V 1.7-selective inhibitors and found critical differences in several factors. Putting aside species differences, most preclinical studies tested young male rodents with limited genetic variability, inconsistent with the clinical population. Inflammatory pain was the most common preclinical chronic pain model whereas nearly all clinical trials focused on neuropathic pain despite some evidence suggesting Na V 1.7 channels are not essential for neuropathic pain. Preclinical studies almost exclusively measured evoked pain whereas most clinical trials assessed average pain intensity without distinguishing between evoked and spontaneous pain. Nearly all preclinical studies gave a single dose of drug unlike the repeat dosing used clinically, thus precluding preclinical data from demonstrating whether tolerance or other slow processes occur. In summary, preclinical testing of Na V 1.7-selective inhibitors aligned poorly with clinical testing. Beyond issues that have already garnered widespread attention in the pain literature, our results highlight the treatment regimen and choice of pain model as areas for improvement.
Indexed as
Identifiers
What OpenQuestion holds
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.