Effects of norepinephrine on microglial neuroinflammation and neuropathic pain

Zou, He‐Lin; Li, Juan; Zhou, Junli; Yi, Xi; Cao, Song

doi:10.1002/ibra.12001

Cited by 7 publications

(7 citation statements)

References 48 publications

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“…Neuropathic pain is often accompanied by neuroinflammation, and relieving neuroinflammation will effectively reduce pain. 29,30 Similar to the results of our previous study, 3 in the present study, we found that CCI mice had significant spinal cord neuroinflammation with increased expression of inflammatory cytokines TNF-α, IL-1β, and IL-6. We used immunofluorescence and found that TNF-α and IL-1β colocalized with microglia.…”

Section: Increased Expression Of Psd-95 In Sdh Affected Phagocytic Mi...supporting

confidence: 91%

Stauntonia chinensis injection relieves neuropathic pain by increasing the expression of PSD‐95 and reducing the proliferation of phagocytic microglia

Deng,

Zou,

Qian

et al. 2023

Ibrain

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Neuroinflammation induced by engulfment of synapses by phagocytic microglia plays a crucial role in neuropathic pain. Stauntonia chinensis is extracted from Stauntonia chinensis DC, which has been used as a traditional Chinese medicine to control trigeminal neuralgia or sciatica. However, the specific anti‐neuralgia mechanism of Stauntonia chinensis is unknown. In this study, the analgesic effect of Stauntonia chinensis injection (SCI) in mice with neuropathic pain and the possible mechanisms are explored. We find that a local injection of 0.1 mL Stauntonia chinensis for 14 days can considerably relieve mechanical hyperalgesia and thermal hyperalgesia in mice with sciatic chronic constriction injury (CCI). Immunofluorescence staining shows that SCI reduces neuroinflammation in the spinal cord of CCI mice. RNA sequencing reveals that the expression of postsynaptic density protein 95 (PSD‐95), a postsynaptic scaffold protein, is downregulated in the spinal cord of CCI mice, but upregulated after SCI administration. Immunofluorescence experiments also demonstrate that SCI administration reverses microglia proliferation and PSD‐95 downregulation in CCI mice. These data suggest that SCI relieves neuropathic pain by increasing the expression of PSD‐95 and reducing the proliferation of phagocytic microglia.

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Section: Increased Expression Of Psd-95 In Sdh Affected Phagocytic Mi...supporting

confidence: 91%

Stauntonia chinensis injection relieves neuropathic pain by increasing the expression of PSD‐95 and reducing the proliferation of phagocytic microglia

Deng,

Zou,

Qian

et al. 2023

Ibrain

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“…However, research has found that sympathetic nerves are involved in the maintenance of many kinds of chronic pain 4 . Therefore, inhibition of sympathetic hyperexcitability may improve the therapeutic effect, which may be related to the involvement of sympathetic nerves in regulating glial inflammation 5 . Among them, intervention of stellate ganglion (SG) is effective for pain in the head, face, neck, upper limbs, or upper chest.…”

Section: Introductionmentioning

confidence: 99%

“…4 Therefore, inhibition of sympathetic hyperexcitability may improve the therapeutic effect, which may be related to the involvement of sympathetic nerves in regulating glial inflammation. 5 Among them, intervention of stellate ganglion (SG) is effective for pain in the head, face, neck, upper limbs, or upper chest. In this review, we summarize the clinical evidence available for the effectiveness of stellate ganglion intervention (SGI), and demonstrate clinical applications of SGI.…”

Section: Introductionmentioning

confidence: 99%

Stellate ganglion intervention for chronic pain: A review

Luo

Wen

Tan

et al. 2022

Ibrain

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Stellate ganglion (SG) intervention is currently widely being studied in many kinds of chronic pain. As one of the convenient ways to treat the sympathetic nervous system, the indications for stellate ganglion intervention (SGI) include complex regional pain syndrome, postherpetic neuralgia, cancer pain of different origins, orofacial pain, and so forth. SGI refers to the reversible or irreversible blocking of the cervical sympathetic trunk, cervical sympathetic ganglion, and their innervation range through noninvasive or minimally invasive treatment. Current treatment options include stellate ganglion block (SGB), SG pulsed radiofrequency, continuous radiofrequency treatment, and noninvasive SGB. In particular, SGB continues to be one of the most studied methods in chronic pain management. However, a single SGB usually provides only short-term effects; repeated SGB may result in complications such as hoarseness, light-headedness, and vessel or nerve injury. Meanwhile, the mechanism of SGI is still unclear. This review discusses the research progress of SGI methods, effectiveness, complications, and possible mechanisms in the management of chronic pain.chronic pain, pulse radiofrequency, stellate ganglion, stellate ganglion block | INTRODUCTIONChronic pain is defined as pain that persists or recurs for more than 3 months, usually accompanied by negative emotions including anxiety and/or depression. 1 Chronic pain severely affects not only physical and mental health but also places a huge economic burden on the family and society. The incidence of chronic pain is reported to be over 30% in China. 2 Current conventional methods for the treatment of chronic pain include drug therapy, minimally invasive therapy, psychotherapy, and physical therapy. 3 However, research has found that sympathetic nerves are involved in the maintenance of many kinds of chronic pain. 4 Therefore, inhibition of sympathetic hyperexcitability may improve the therapeutic effect, which may be related to the involvement of sympathetic nerves in regulating glial inflammation. 5 Among them, intervention of stellate ganglion (SG) is effective for pain in the head, face, neck, upper limbs, or upper chest. In this review, we summarize the clinical evidence available for the effectiveness of stellate ganglion intervention (SGI), and demonstrate clinical applications of SGI.

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“…It's assumed that NE extracellular levels are reduced since NE tissue levels are depleted after DSP-4 treatment; however, some reports have challenged this idea, showing that DSP-4 treatment signi cantly increases extracellular levels of NE in the brain [19,[26][27][28]. This could explain our results showing DSP-4-mediated protection in the context of hα-SYN mediated neurotoxicity since increased NE signaling in the brain is associated with a reduction in neuroin ammation and neuronal degeneration in vitro and in vivo [48,49]. This hypothesis is supported by the observation that blocking the β-ARs using propranolol, reverses DSP-4 protection of dopaminergic neurons after hα-SYN overexpression.…”

Section: Discussionmentioning

confidence: 75%

Opposing effects of β-2 and β-1 adrenergic receptor signaling on neuroinflammation and dopaminergic neuron survival in α-synuclein-mediated neurotoxicity

Torrente

Schielke

et al. 2022

Preprint

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Background Noradrenergic neurons in the locus coeruleus (LC) are the primary source of norepinephrine (NE) in the brain and degeneration of these neurons is reported in the early stages of Parkinson’s disease (PD), even prior to dopaminergic neuron degeneration in the substantia nigra (SN), which is a hallmark of PD pathology. NE depletion is generally associated with increased PD pathology in neurotoxin-based PD models. The effect of NE depletion in other models of PD like α-synuclein-based models is largely unexplored. In PD models and in human patients, β-adrenergic receptors (AR) signaling is associated with a reduction of neuroinflammation and PD pathology. However, the effect of NE depletion in the brain and the extent of NE and β-ARs signaling involvement in neuroinflammation, and dopaminergic neuron survival is poorly understood. Methods Two mouse models of PD, a 6OHDA neurotoxin-based model and a human α-synuclein (hα-SYN) virus-based model of PD were used. DSP-4 was used to deplete NE levels in the brain and its effect was confirmed by HPLC with electrochemical detection. A pharmacological approach was used to mechanistically understand the impact of DSP-4 in the hα-SYN model of PD using a norepinephrine transporter (NET) and a β-AR blocker. Epifluorescence and confocal imaging were used to study changes in microglia activation and T-cell infiltration after β1-AR and β2-AR agonist treatment in the hα-SYN virus-based model of PD. Results Consistent with previous studies we found that DSP-4 pretreatment increased dopaminergic neuron loss after 6OHDA injection. In contrast, DSP-4 pretreatment protected dopaminergic neurons after hα-SYN overexpression. DSP-4-mediated protection of dopaminergic neurons after hα-SYN overexpression was dependent on β-AR signaling since using a β-AR blocker prevented DSP-4-mediated dopaminergic neuron protection in this model of PD. Finally, we found that the β-2AR agonist, clenbuterol, reduced microglia activation, T-cell infiltration, and dopaminergic neuron degeneration whereas xamoterol a β-1AR agonist showed increased neuroinflammation and dopaminergic neuron degeneration in the context of hα-SYN-mediated neurotoxicity. Conclusion Our data demonstrate that the effects of DSP-4 on dopaminergic neuron degeneration are model specific, and suggest that in the context of α-SYN driven neuropathology β2-AR specific agonists may have therapeutic benefit in PD.

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Effects of norepinephrine on microglial neuroinflammation and neuropathic pain

Cited by 7 publications

References 48 publications

Stauntonia chinensis injection relieves neuropathic pain by increasing the expression of PSD‐95 and reducing the proliferation of phagocytic microglia

Stauntonia chinensis injection relieves neuropathic pain by increasing the expression of PSD‐95 and reducing the proliferation of phagocytic microglia

Stellate ganglion intervention for chronic pain: A review

Opposing effects of β-2 and β-1 adrenergic receptor signaling on neuroinflammation and dopaminergic neuron survival in α-synuclein-mediated neurotoxicity

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