ArticleMolecular pain2013
BDNF regulates atypical PKC at spinal synapses to initiate and maintain a centralized chronic pain state.
Article in Molecular pain, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 94 citations in OpenAlex.
- Microtubule Cytoskeleton Dysfunction in Chronic Pain: Mechanisms of Transport Failure and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Role of Brain Derived Neurotrophic Factor and Related Therapeutic Strategies in Central Post-Stroke Pain.Neurochemical research · 2024Review
- Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.Brain, behavior, and immunity · 2024Article
- Article
- Brain-Derived Neurotrophic Factor, Nociception, and Pain.Biomolecules · 2024Review
- Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.bioRxiv : the preprint server for biology · 2023Article
- Autonomic nervous system markers of music-elicited analgesia in people with fibromyalgia: A double-blind randomized pilot study.Frontiers in pain research (Lausanne, Switzerland) · 2022Article
- Neurotrophic Treatment Initiated During Early Postnatal Development Prevents the Alzheimer-Like Behavior and Synaptic Dysfunction.Journal of Alzheimer's disease : JAD · 2021Article
- Sculpting Dendritic Spines during Initiation and Maintenance of Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Review
- Spinal Wnt5a Plays a Key Role in Spinal Dendritic Spine Remodeling in Neuropathic and Inflammatory Pain Models and in the Proalgesic Effects of Peripheral Wnt3a.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Blockade of BDNF signalling attenuates chronic visceral hypersensitivity in an IBS-like rat model.European journal of pain (London, England) · 2020Article
- Impaired AMPK‑CGRP signaling in the central nervous system contributes to enhanced neuropathic pain in high‑fat diet‑induced obese rats, with or without nerve injury.Molecular medicine reports · 2019Article
- Sex differences in learned conditioned pain sensitivity.Lab animal · 2019Article
- TIMP-1 Attenuates the Development of Inflammatory Pain Through MMP-Dependent and Receptor-Mediated Cell Signaling Mechanisms.Frontiers in molecular neuroscience · 2019Article
- Transcriptional Profiling of Non-injured Nociceptors After Spinal Cord Injury Reveals Diverse Molecular Changes.Frontiers in molecular neuroscience · 2019Article
- Autocrine signaling by anProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Influence of intrathecal injection with dexmedetomidine on the behavioral ability and analgesic effects on rats with neuropathic pain and expression of protein kinase C in the spinal dorsal horn.Experimental and therapeutic medicine · 2018Article
- Opposing Roles of Estradiol and Testosterone on Stress-Induced Visceral Hypersensitivity in Rats.The journal of pain · 2018Article
- Brain-derived neurotrophic factor derived from sensory neurons plays a critical role in chronic pain.Brain : a journal of neurology · 2018Article
- PKMζ Is Not Required for Development of Postsurgical Pain.Molecular neurobiology · 2018Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundChronic pain is an important medical problem affecting hundreds of millions of people worldwide. Mechanisms underlying the maintenance of chronic pain states are poorly understood but the elucidation of such mechanisms have the potential to reveal novel therapeutics capable of reversing a chronic pain state. We have recently shown that the maintenance of a chronic pain state is dependent on an atypical PKC, PKMζ, but the mechanisms involved in controlling PKMζ in chronic pain are completely unknown. Here we have tested the hypothesis that brain derived neurotrophic factor (BDNF) regulates PKMζ, and possibly other aPKCs, to maintain a centralized chronic pain state.
resultsWe first demonstrate that although other kinases play a role in the initiation of persistent nociceptive sensitization, they are not involved in the maintenance of this chronic pain state indicating that a ZIP-reversible process is responsible for the maintenance of persistent sensitization. We further show that BDNF plays a critical role in initiating and maintaining persistent nociceptive sensitization and that this occurs via a ZIP-reversible process. Moreover, at spinal synapses, BDNF controls PKMζ and PKCλ nascent synthesis via mTORC1 and BDNF enhances PKMζ phosphorylaton. Finally, we show that BDNF signaling to PKMζ and PKCλ is conserved across CNS synapses demonstrating molecular links between pain and memory mechanisms.
conclusionsHence, BDNF is a key regulator of aPKC synthesis and phosphorylation and an essential mediator of the maintenance of a centralized chronic pain state. These findings point to BDNF regulation of aPKC as a potential therapeutic target for the permanent reversal of a chronic pain state.
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