ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2018
Neuropathic Pain Creates an Enduring Prefrontal Cortex Dysfunction Corrected by the Type II Diabetic Drug Metformin But Not by Gabapentin.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04089813 (Effect of Metformin on Chronic Pain After Thoracic Surgery in Diabetic Patients), which is not on this map. Cited by 59 papers.
What it found
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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.
Effect of Metformin on Chronic Pain After Thoracic Surgery in Diabetic Patients
Who cites it
59 citing papers in PubMed, 81 citations in OpenAlex.
- Effectiveness of oral clonidine and gabapentin on peripheral neuropathy in diabetic patients in southwestern Iran: a randomized clinical trial.BMC endocrine disorders · 2023Trial
- The Effect of Metformin on Chemotherapy-Induced Toxicities in Non-diabetic Breast Cancer Patients: A Randomised Controlled Study.Drug safety · 2023Trial
- Gabapentin and cognitive impairment after traumatic brain injury: A multinational cohort of 49,925 patients.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Chronic neuropathic pain alters reversal learning and prefrontal cortex activation without generalized deficits in reward-related behavior.bioRxiv : the preprint server for biology · 2026Article
- Subtype-Specific Roles of Anterior Cingulate Cortex Neurons in Pain-Induced Social Deficits in Mice.Theranostics · 2026Article
- Recent progress in chronic pain-related negative emotions and cognitive dysfunction: insights into the mechanisms underlying neural circuitry.Frontiers in cellular neuroscience · 2026Review
- Endoplasmic Reticulum Stress Mediates Axon Initial Segment Shortening: Implications for Diabetic Brain Complications.Journal of molecular neuroscience : MN · 2025Article
- Impaired WNT3/IGF-1 Signaling in Dorsal Dentate Gyrus Contributes to Chronic Pain-Related Cognitive Impairment.CNS neuroscience & therapeutics · 2025Article
- Association of nociplastic pain with executive function decline in a longitudinal cohort of middle-age adults: a prospective cohort study.British journal of anaesthesia · 2025Article
- Environmental enrichment alleviates neuropathic pain-associated anxiety by enhancing the function of parvalbumin interneurons in the anterior cingulate cortex.Scientific reports · 2025Article
- Bidirectional modulation of somatostatin-expressing interneurons in the basolateral amygdala reduces neuropathic pain perception in mice.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Chronic pain and cognitive dysfunction: clinical manifestations, underlying mechanisms, and emerging therapeutic strategies.Frontiers in neuroscience · 2025Review
- Chronic Pain-Related Cognitive Deficits: Preclinical Insights into Molecular, Cellular, and Circuit Mechanisms.Molecular neurobiology · 2024Review
- Article
- Targeting Prefrontal Cortex Dysfunction in Pain.The Journal of pharmacology and experimental therapeutics · 2024Review
- NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice.Nature communications · 2024Article
- Restoration of the Activity of the Prefrontal Cortex to the Nucleus Accumbens Core Pathway Relieves Fentanyl-Induced Hyperalgesia in Male Rats.Journal of pain research · 2024Article
- Activation of the TNF-α-Necroptosis Pathway in Parvalbumin-Expressing Interneurons of the Anterior Cingulate Cortex Contributes to Neuropathic Pain.International journal of molecular sciences · 2023Article
- Pain-related cortico-limbic plasticity and opioid signaling.Neuropharmacology · 2023Review
- Pain-induced adaptations in the claustro-cingulate pathway.Cell reports · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Chronic pain patients suffer from pain-related cognitive deficits, even when taking commonly prescribed analgesics. These deficits are likely related to pain-related maladaptive plasticity in the frontal cortex. We sought to model cognitive deficits in mice with neuropathic pain to examine maladaptive morphological plasticity in the mPFC and to assess the effects of several therapeutics. We used an attentional set-shifting task in mice with spared nerve injury (SNI) who received either a single intrathecal injection of an analgesic dose of clonidine, 7 d of 100 mg/kg gabapentin, or 7 d of 200 mg/kg metformin. Male SNI mice were significantly more impaired in the set-shifting task than females. This deficit correlated with a loss of parvalbumin (PV) and reductions in axon initial segment (AIS) length in layers 5/6 of the infralimbic (IL) cortex. Acute pain relief with clonidine had no effect on set-shifting performance, whereas pain relief via 7 day treatment with gabapentin worsened the impairment in both SNI and sham mice. Gabapentin reversed the PV loss in the IL but had no effect on AIS length. Treatment with the AMPK-activator metformin completely reversed the pain-related cognitive impairment and restored AIS length in the IL but had little effect on PV expression. Our findings reveal that neuropathic pain-related cognitive impairments in male mice are correlated to bilateral morphological changes in PV interneurons and layer 5/6 IL pyramidal neuron AIS. Pain relief with metformin can reverse some of the functional and anatomical changes.
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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.