ArticlePain2018
The stress regulator FKBP51: a novel and promising druggable target for the treatment of persistent pain states across sexes.
Article in Pain, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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
33 citing papers in PubMed, 63 citations in OpenAlex.
- FKBP51 inhibition by SAFit2 modulates tau pathology and cognitive deficits in PS19 mice.Alzheimer's research & therapy · 2026Article
- Transcriptome of the human C2 dorsal root ganglia in C1-2 arthrodesis surgery: insight for neck pain.Brain : a journal of neurology · 2026Article
- Article
- Analgesia through FKBP51 inhibition at disease onset confers lasting relief from sensory and emotional chronic pain symptoms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Differences in multidimensional phenotype of 2 joint pain models link early weight-bearing deficit to late depressive-like behavior in male mice.Pain reports · 2024Article
- Gene expression in the dorsal root ganglion and the cerebrospinal fluid metabolome in polyneuropathy and opioid tolerance in rats.IBRO neuroscience reports · 2024Article
- Risk Factors for Increased Opioid Use During Postoperative Intensive Care.Critical care explorations · 2024Observational
- Automated Flow Peptide Synthesis Enables Engineering of Proteins with Stabilized Transient Binding Pockets.ACS central science · 2024Article
- Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.Physiological reviews · 2024Review
- Dysregulation of sphingolipid metabolism in pain.Frontiers in pharmacology · 2024Review
- Preparation of Nanosized Pharmaceutical Formulations by Dual Centrifugation.Pharmaceuticals (Basel, Switzerland) · 2023Review
- A DNA methylation signature in the stress driver gene Fkbp5 indicates a neuropathic component in chronic pain.Clinical epigenetics · 2023Article
- FKBP5 inhibitors modulate alcohol drinking and trauma-related behaviors in a model of comorbid post-traumatic stress and alcohol use disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- SAFit2 ameliorates paclitaxel-induced neuropathic pain by reducing spinal gliosis and elevating pro-resolving lipid mediators.Journal of neuroinflammation · 2023Article
- Analysis of the Selective Antagonist SAFit2 as a Chemical Probe for the FK506-Binding Protein 51.ACS pharmacology & translational science · 2023Review
- The FKBP51 Inhibitor SAFit2 Restores the Pain-Relieving C16 Dihydroceramide after Nerve Injury.International journal of molecular sciences · 2022Article
- SAFit2 reduces neuroinflammation and ameliorates nerve injury-induced neuropathic pain.Journal of neuroinflammation · 2022Article
- Duration of Reduction in Enduring Stress-Induced Hyperalgesia Via FKBP51 Inhibition Depends on Timing of Administration Relative to Traumatic Stress Exposure.The journal of pain · 2022Article
- Hippocampal volume, FKBP5 genetic risk alleles, and childhood trauma interact to increase vulnerability to chronic multisite musculoskeletal pain.Scientific reports · 2022Article
- FKBP51 and the molecular chaperoning of metabolism.Trends in endocrinology and metabolism: TEM · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
It is well established that FKBP51 regulates the stress system by modulating the sensitivity of the glucocorticoid receptor to stress hormones. Recently, we have demonstrated that FKBP51 also drives long-term inflammatory pain states in male mice by modulating glucocorticoid signalling at spinal cord level. Here, we explored the potential of FKBP51 as a new pharmacological target for the treatment of persistent pain across the sexes. First, we demonstrated that FKBP51 regulates long-term pain states of different aetiologies independently of sex. Deletion of FKBP51 reduced the mechanical hypersensitivity seen in joint inflammatory and neuropathic pain states in female and male mice. Furthermore, FKBP51 deletion also reduced the hypersensitivity seen in a translational model of chemotherapy-induced pain. Interestingly, these 3 pain states were associated with changes in glucocorticoid signalling, as indicated by the increased expression, at spinal cord level, of the glucocorticoid receptor isoform associated with glucocorticoid resistance, GRβ, and increased levels of plasma corticosterone. These pain states were also accompanied by an upregulation of interleukin-6 in the spinal cord. Crucially, we were able to pharmacologically reduce the severity of the mechanical hypersensitivity seen in these 3 models of persistent pain with the unique FKBP51 ligand SAFit2. When SAFit2 was combined with a state-of-the-art vesicular phospholipid gel formulation for slow release, a single injection of SAFit2 offered pain relief for at least 7 days. We therefore propose the pharmacological blockade of FKBP51 as a new approach for the treatment of persistent pain across sexes, likely in humans as well as rodents.
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.