ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Maladaptive dendritic spine remodeling contributes to diabetic neuropathic pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 114 citations in OpenAlex.
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- Dorsal root ganglion neuromodulation restores accumbal gate to inhibit mechanical allodynia.The journal of headache and pain · 2026Article
- A comprehensive review on adaptive plasticity and recovery mechanisms post-acquired brain injury.Neuroprotection (Chichester, England) · 2025Review
- Increased Expression of Synaptic Vesicle Glycoprotein 2A (SV2A) in the Brain of Chronic Diabetic Rats.Synapse (New York, N.Y.) · 2025Article
- The analgesic mechanism of electroacupuncture at the central level for neuropathic pain: a review of studies based on animal experiments.Frontiers in neurology · 2025Review
- The diversity and plasticity of descending motor pathways rewired after stroke and trauma in rodents.Frontiers in neural circuits · 2025Review
- Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain.Frontiers in immunology · 2025Review
- Understanding of Spinal Wide Dynamic Range Neurons and Their Modulation on Pathological Pain.Journal of pain research · 2024Review
- Tiam1 coordinates synaptic structural and functional plasticity underpinning the pathophysiology of neuropathic pain.Neuron · 2023Article
- Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses.Small GTPases · 2022Article
- The mechanism of exercise for pain management in Parkinson's disease.Frontiers in molecular neuroscience · 2022Review
- Recent updates in the treatment of diabetic polyneuropathy.Faculty reviews · 2022Review
- The consequence of endothelial remodelling on the blood spinal cord barrier and nociception.Current research in physiology · 2022Review
- Chronic VEGFR-3 signaling preserves dendritic arborization and sensitization under stress.Brain, behavior, and immunity · 2021Article
- Dendritic Spine Initiation in Brain Development, Learning and Diseases and Impact of BAR-Domain Proteins.Cells · 2021Review
- Characterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line.Scientific reports · 2021Article
- Conditional RAC1 knockout in motor neurons restores H-reflex rate-dependent depression after spinal cord injury.Scientific reports · 2021Article
- Proteomic Modulation in the Dorsal Spinal Cord Following Spinal Cord Stimulation Therapy in an In Vivo Neuropathic Pain Model.Neuromodulation : journal of the International Neuromodulation Society · 2021Article
- Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals.Diabetes & metabolism journal · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic neuropathic pain imposes a huge burden on individuals and society, and represents a major public health problem. Despite aggressive efforts, diabetic neuropathic pain is generally refractory to available clinical treatments. A structure-function link between maladaptive dendritic spine plasticity and pain has been demonstrated previously in CNS and PNS injury models of neuropathic pain. Here, we reasoned that if dendritic spine remodeling contributes to diabetic neuropathic pain, then (1) the presence of malformed spines should coincide with the development of pain, and (2) disrupting maladaptive spine structure should reduce chronic pain. To determine whether dendritic spine remodeling contributes to neuropathic pain in streptozotocin (STZ)-induced diabetic rats, we analyzed dendritic spine morphology and electrophysiological and behavioral signs of neuropathic pain. Our results show changes in dendritic spine shape, distribution, and shape on wide-dynamic-range (WDR) neurons within lamina IV-V of the dorsal horn in diabetes. These diabetes-induced changes were accompanied by WDR neuron hyperexcitability and decreased pain thresholds at 4 weeks. Treatment with NSC23766 (N(6)-[2-[[4-(diethylamino)-1-methylbutyl]amino]-6-methyl-4-pyrimidinyl]-2-methyl-4,6-quinolinediamine trihydrochloride), a Rac1-specific inhibitor known to interfere with spine plasticity, decreased the presence of malformed spines in diabetes, attenuated neuronal hyperresponsiveness to peripheral stimuli, reduced spontaneous firing activity from WDR neurons, and improved nociceptive mechanical pain thresholds. At 1 week after STZ injection, animals with hyperglycemia with no evidence of pain had few or no changes in spine morphology. These results demonstrate that diabetes-induced maladaptive dendritic spine remodeling has a mechanistic role in neuropathic pain. Molecular pathways that control spine morphogenesis and plasticity may be promising future targets for treatment.
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