ArticleMolecular pain
Mitochondrial superoxide increases excitatory synaptic strength in spinal dorsal horn neurons of neuropathic mice.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- The Wnt5a-PKCδ-GluA1 axis controls synapse-specific plasticity in HIV-1 gp120-induced pain pathogenesis.Brain : a journal of neurology · 2026Article
- Lanthionine synthetase C-like protein 1 (LanCL1): a therapeutic target for neuropathic pain.Pain · 2026Article
- Mitochondrial dysfunction at the intersection of alcohol use disorder and chronic pain.Function (Oxford, England) · 2026Review
- Post-Herpetic Neuralgia: Review of Pathophysiology, Mechanisms, and Drug Treatment.Current neuropharmacology · 2026Review
- Enhancing peripheral nerve regeneration with rehabilitation and biomaterial-driven drug delivery strategies.Progress in biomedical engineering (Bristol, England) · 2025Review
- Electroacupuncture Alleviates Neuropathic Pain by Suppressing Ferroptosis in Dorsal Root Ganglion via SAT1/ALOX15 Signaling.Molecular neurobiology · 2023Article
- Intrathecal liproxstatin-1 delivery inhibits ferroptosis and attenuates mechanical and thermal hypersensitivities in rats with complete Freund's adjuvant-induced inflammatory pain.Neural regeneration research · 2023Article
- Development of opioid-induced hyperalgesia depends on reactive astrocytes controlled by Wnt5a signaling.Molecular psychiatry · 2023Article
- Neuropathic pain; what we know and what we should do about it.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice.The Journal of clinical investigation · 2022Article
- A neuron-to-astrocyte Wnt5a signal governs astrogliosis during HIV-associated pain pathogenesis.Brain : a journal of neurology · 2022Article
- Neuropathogenesis of HIV and emerging therapeutic targets.Expert opinion on therapeutic targets · 2022Review
- The role of PPARγ in chemotherapy-evoked pain.Neuroscience letters · 2021Review
- Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model.Frontiers in synaptic neuroscience · 2021Article
- Blockers of Wnt3a, Wnt10a, or β-Catenin Prevent Chemotherapy-Induced Neuropathic Pain In Vivo.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Excessive Accumulation of CaFrontiers in physiology · 2019Article
- Mechanism of electrothermal acupuncture in alleviating postherpetic neuralgia.Frontiers in neurologyArticle
- Understanding the kynurenine pathway: A narrative review on its impact across chronic pain conditions.Molecular painReview
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
Reactive oxygen species has been suggested as a key player in neuropathic pain, causing central sensitization by changing synaptic strengths in spinal dorsal horn neurons. However, it remains unclear as to what type of reactive oxygen species changes what aspect of synaptic strengths for central sensitization in neuropathic pain conditions. In this study, we investigated whether mitochondrial superoxide affects both excitatory and inhibitory synaptic strengths in spinal dorsal horn neurons after peripheral nerve injury. Upregulation of mitochondrial superoxide level by knockout of superoxide dismutase-2 exacerbated neuropathic mechanical hypersensitivity caused by L5 spinal nerve ligation, whereas downregulation of mitochondrial superoxide level by overexpression of superoxide dismutase-2 alleviated the hypersensitivity. In spinal nerve ligation condition, the frequency of miniature excitatory postsynaptic currents increased, while that of miniature inhibitory postsynaptic currents decreased in spinal dorsal horn neurons. Superoxide dismutase-2-knockout augmented, whereas superoxide dismutase-2-overexpression prevented, the spinal nerve ligation-increased miniature excitatory postsynaptic currents frequency. However, superoxide dismutase-2-knockout had no effect on the spinal nerve ligation-decreased miniature inhibitory postsynaptic current frequency, and superoxide dismutase-2-overexpression unexpectedly decreased miniature inhibitory postsynaptic current frequency in the normal condition. When applied to the spinal cord slice during in vitro recordings, mitoTEMPO, a specific scavenger of mitochondrial superoxide, reduced the spinal nerve ligation-increased miniature excitatory postsynaptic currents frequency but failed to normalize the spinal nerve ligation-decreased miniature inhibitory postsynaptic current frequency. These results suggest that in spinal dorsal horn neurons, high levels of mitochondrial superoxide increase excitatory synaptic strength after peripheral nerve injury and contribute to neuropathic mechanical hypersensitivity. However, mitochondrial superoxide does not seem to be involved in the decreased inhibitory synaptic strength in this neuropathic pain condition.
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