Reactive oxygen species affect spinal cell type-specific synaptic plasticity in a model of neuropathic pain

Bittar, Alice; Jun, Joong-Hwan; La, Jun–Ho; Wang, Jigong; Leem, Joong Woo; Chung, Jin Mo

doi:10.1097/j.pain.0000000000001014

Cited by 54 publications

(52 citation statements)

References 42 publications

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“… 2 Our previous studies showed that ROS induces and maintains long-term changes in excitatory postsynaptic responses in spinal dorsal horn neurons in a cell type-specific manner, potentiating the responses in excitatory projection neurons but suppressing them in GABAergic inhibitory neurons. 3 At a behavioral level, reducing ROS with scavengers such as phenyl-N-tert-butylnitrone and 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) alleviates neuropathic mechanical pain 4 – 6 and capsaicin-induced secondary mechanical hypersensitivity that is also attributed to central sensitization. 7 – 9 …”

Section: Introductionmentioning

confidence: 99%

Mitochondrial superoxide increases excitatory synaptic strength in spinal dorsal horn neurons of neuropathic mice

et al. 2018

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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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Section: Introductionmentioning

confidence: 99%

Mitochondrial superoxide increases excitatory synaptic strength in spinal dorsal horn neurons of neuropathic mice

et al. 2018

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“…70 Reactive oxygen species (ROS) play a dual role in physiological and pathophysiological reactions, and have been used extensively in different inflammatory and neuropathic pain models. 71,72 Electrophysiological and behavioral studies have been performed to address the role of ROS in the central nucleus of amygdala in a visceral pain model induced by intracolonic zymosan. 73 and increased blood pressure and heart rates can be measured by electromyography and surgical implantation of an arterial catheter, respectively.…”

Section: Electrophysiologymentioning

confidence: 99%

Possible implications of animal models for the assessment of visceral pain

Regmi

Shah

2020

Anim Models and Exp Med

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Visceral pain is the most common but challenging problem seen in clinical patients. Approximately a quarter to a half of the world population experience visceral pain at least once during their life span, which leads to substantial health care costs. 1 Inflammation, ischemia, or mesenteric stretching or distention of the hollow organs of the thoracic, pelvic, or abdominal cavities stimulate the afferent nociceptors to activate the pain pathways. 2 The activated fibers transmit the nociceptive signals to the spinal dorsal horn (SDH) and then to the central nervous system (CNS), resulting in visceral pain. 3 Visceral pain is diffuse in nature and is thereby very difficult to localize. 4,5

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“…ROS was identified as a pivotal modulator factor in immune system, neural system, infection and cancer development [ 24 – 27 ]. ROS homeostasis is essential in the sustain of cells function.…”

Section: Ros and Oxidative Stressmentioning

confidence: 99%

Cell toxicity mechanism and biomarker

Zhang

2018

Clinical & Translational Med

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Cell toxicity may result in organ dysfunction and cause severe health problem. Recent studies revealed many toxicants may induced the over production of Nitric oxide, reactive oxygen species and the subsequent oxidative stress, cause cell toxicity. Mitochondrion dysfunction maybe the subsequent consequence of oxidative stress and has been recognized as another contributing factor in cell toxicity. Besides, oxidative products induced by some toxicants may also produce the compounds that damage cell DNA, leading to toxicity. Especially, the significance of nanoparticle induced cell toxicity was disclosed recently and attract more concern. The mechanism mainly includes inflammation, oxidative stress and DNA damage. On the other side, some biomarkers of cell toxicity including autophagy, cytokines, miRNA has been identified. The understanding of these phenomenon may enable us to clarify the cell toxicity mechanism then contribute to cell toxicity protection, disease treatment and drug side effect prevention.

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Reactive oxygen species affect spinal cell type-specific synaptic plasticity in a model of neuropathic pain

Cited by 54 publications

References 42 publications

Mitochondrial superoxide increases excitatory synaptic strength in spinal dorsal horn neurons of neuropathic mice

Mitochondrial superoxide increases excitatory synaptic strength in spinal dorsal horn neurons of neuropathic mice

Possible implications of animal models for the assessment of visceral pain

Cell toxicity mechanism and biomarker

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