ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017
Loss of M1 Receptor Dependent Cholinergic Excitation Contributes to mPFC Deactivation in Neuropathic Pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 56 citations in OpenAlex.
- Article
- A molecularly defined basalo-prefrontal-thalamic circuit regulates sensory and affective dimensions of pain in male mice.Nature communications · 2026Article
- Chronic Pain-Related Cognitive Deficits: Preclinical Insights into Molecular, Cellular, and Circuit Mechanisms.Molecular neurobiology · 2024Review
- Targeting Prefrontal Cortex Dysfunction in Pain.The Journal of pharmacology and experimental therapeutics · 2024Review
- Hypernegative GABAThe journal of pain · 2024Article
- A mesocortical glutamatergic pathway modulates neuropathic pain independent of dopamine co-release.Nature communications · 2024Article
- Corticotropin-releasing hormone neurons control trigeminal neuralgia-induced anxiodepression via a hippocampus-to-prefrontal circuit.Science advances · 2024Article
- Pain Comorbidities with Attention Deficit: A Narrative Review of Clinical and Preclinical Research.Journal of pain research · 2024Review
- Pain-related cortico-limbic plasticity and opioid signaling.Neuropharmacology · 2023Review
- Oxytocin promotes prefrontal population activity via the PVN-PFC pathway to regulate pain.Neuron · 2023Article
- HCN-Channel-Dependent Hyperexcitability of the Layer V Pyramidal Neurons in IL-mPFC Contributes to Fentanyl-Induced Hyperalgesia in Male Rats.Molecular neurobiology · 2023Article
- Impaired muscarinic modulation of the rat prelimbic cortex in neuropathic pain is sexually dimorphic and associated with cold allodynia.Frontiers in cellular neuroscience · 2023Article
- Activation of VIP interneurons in the prefrontal cortex ameliorates neuropathic pain aversiveness.Cell reports · 2022Article
- Cholinergic basal forebrain nucleus of Meynert regulates chronic pain-like behavior via modulation of the prelimbic cortex.Nature communications · 2022Article
- Closed-loop stimulation using a multiregion brain-machine interface has analgesic effects in rodents.Science translational medicine · 2022Article
- Restoration of FMRP expression in adult V1 neurons rescues visual deficits in a mouse model of fragile X syndrome.Protein & cell · 2022Article
- Antinociceptive Effects and Interaction Mechanisms of Intrathecal Pentazocine and Neostigmine in Two Different Pain Models in Rats.Pain research & management · 2022Article
- Article
- Pharmacological restoration of anti-nociceptive functions in the prefrontal cortex relieves chronic pain.Progress in neurobiology · 2021Article
- Neural Plasticity in the Brain during Neuropathic Pain.Biomedicines · 2021Review
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
In chronic pain, the medial prefrontal cortex (mPFC) is deactivated and mPFC-dependent tasks such as attention and working memory are impaired. We investigated the mechanisms of mPFC deactivation in the rat spared nerve injury (SNI) model of neuropathic pain. Patch-clamp recordings in acute slices showed that, 1 week after the nerve injury, cholinergic modulation of layer 5 (L5) pyramidal neurons was severely impaired. In cells from sham-operated animals, focal application of acetylcholine induced a left shift of the input/output curve and persistent firing. Both of these effects were almost completely abolished in cells from SNI-operated rats. The cause of this impairment was an ∼60% reduction of an M1-coupled, pirenzepine-sensitive depolarizing current, which appeared to be, at least in part, the consequence of M1 receptor internalization. Although no changes were detected in total M1 protein or transcript, both the fraction of the M1 receptor in the synaptic plasma membrane and the biotinylated M1 protein associated with the total plasma membrane were decreased in L5 mPFC of SNI rats. The loss of excitatory cholinergic modulation may play a critical role in mPFC deactivation in neuropathic pain and underlie the mPFC-specific cognitive deficits that are comorbid with neuropathic pain.
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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.