NR2B-Tyr phosphorylation regulates synaptic plasticity in central sensitization in a chronic migraine rat model

Wang, Xue Ying; Zhou, Hui; Wang, Sha; Liu, Chao Yang; Qin, Guang Cheng; Fu, Qing Qing; Zhou, Ji; Chen, Li Xue

doi:10.1186/s10194-018-0935-2

Cited by 59 publications

(62 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3b, c). In addition, phosphorylation and activation of NR2B in the spine are vital in the maintenance of central sensitization and mechanical allodynia [35,36]. Results of western blot showed that DSS treatment notably increased phosphorylation of NR2B in the spinal cord from day 7 to day 21, which was consistent with the changes of PWMT (Fig.…”

Section: Acute Colonic Inflammation Leads To Persistent Pain Increassupporting

confidence: 73%

Pioglitazone Attenuates Experimental Colitis-Associated Hyperalgesia through Improving the Intestinal Barrier Dysfunction

et al. 2020

View full text Add to dashboard Cite

Impaired intestinal mucosal integrity during colitis involves the peroxisome proliferator-activated receptor-γ (PPARγ), an important anti-inflammatory factor in intestinal mucosa homoeostasis, which is a potential target in colitis. Recurrent chronic pain is a vital pathogenetic feature of colitis. Nevertheless, potential functions of PPARγ in the colitis-associated hyperalgesia remain unclear. This study aimed to investigate biological roles of pioglitazone in relieving colitis-associated pain hypersensitivity by a PPARγ tight junction protein-dependent mechanism during the course of dextran sodium sulfate (DSS)-induced intestinal inflammation. The DSS-induced colitis model was generated in C57BL/6 mice. Changes in colitis induced the injury of intestinal mucosal barrier and hyperalgesia after a 6-day treatment of pioglitazone (25 mg/kg, IP injection) were assessed through immunofluorescent, hematoxylin and eosin (H&E) staining, western blot analysis, and determination of paw withdrawal mechanical threshold. A significant reduction of paw withdrawal mechanical threshold occurred after DSS treatment. Follow-up data showed that systematic administration of PPARγ agonist pioglitazone ameliorated the DSS-induced colitis and the development of colitis-associated hyperalgesia by repairing the intestinal mucosal barrier. The tight junction proteins ZO-1 and Claudin-5 were upregulated by PPARγ signaling, which in turn promoted the improvement of intestinal barrier function. Moreover, pioglitazone inhibited phosphorylation of ERK and NF-κB in the colon and decreased the levels of inflammatory cytokines in both colon spine tissues. Furthermore, systemically pioglitazone treatment inhibited the activation of microglia and astrocytes, as well as DSSinduced phosphorylation of NR2B subunit in spinal cord, which was correspondingly consistent with the pain behavior. Pioglitazone ameliorates DSS-induced colitis and attenuates colitis-associated mechanical hyperalgesia, with improving integrity of the Yulin Huang and Chenchen Wang contributed equally to this work.

show abstract

Section: Acute Colonic Inflammation Leads To Persistent Pain Increassupporting

confidence: 73%

Pioglitazone Attenuates Experimental Colitis-Associated Hyperalgesia through Improving the Intestinal Barrier Dysfunction

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The migraine rat model in our study was similar to that employed in previous studies, [15][16][17][22][23][24][25] where IS was applied to produce a significant and stable reduction of the cutaneous receptive field pain threshold by activating the trigeminovascular system. Interestingly, this effect shows no bilateral facial difference.…”

Section: Discussionmentioning

confidence: 99%

“…Otherwise, a dural inflammatory soup (IS) injection is used to initiate migraine attacks and induce hyperalgesia and allodynia in the receptive field of the periorbital region of trigeminal nerve, using mechanical pain threshold test with a Von-Frey filament. 15,[22][23][24][25] Mechanical CCH may develop solely within the periorbital region and may spread throughout the face, scalp, limbs, and body. In addition to this, mechanical stimulation can induce skin pain, including hyperresponsiveness and hypersensitivity, which is either accompanied by a migraine attack or is interictal to it.…”

Section: Introductionmentioning

confidence: 99%

<p>Prophylactic Electroacupuncture on the Upper Cervical Segments Decreases Neuronal Discharges of the Trigeminocervical Complex in Migraine-Affected Rats: An in vivo Extracellular Electrophysiological Experiment</p>

Liu

Zhao

et al. 2020

JPR

View full text Add to dashboard Cite

Purpose: This rat experiment aims to demonstrate the efficacy of electrical acupuncture in preventing migraine attacks by stimulating the acupoint GB20. Introduction: Migraine, which takes 2ed at level four causes of GBD's disease hierarchy, becomes a public health issue. It is important for physicians to supplement their knowledge of its treatment and consider alternative methods of therapy, such as acupuncture. However, the neurobiological and pathophysiological mechanisms of this prophylactic effect were unclear. The trigeminocervical complex is thought to be an important relay station in migraine pathophysiology as the key nuclei of the trigeminovascular system and the brainstem descending pain modulation system. Methods: There were six groups involved in this study: control, model, electroacupuncture, non-acupoint electroacupuncture, saline+electroacupuncture and saline+non-acupoint electroacupuncture. We injected saline or inflammatory soup into dura mater to induce control or migraine in the rats. The mechanical pain threshold and the single-cell extraneural neurophysiology of the C1 spinal dorsal horn neurons in the trigeminocervical complex were detected. Results: Pre-electroacupuncture could significantly increase the mechanical pain threshold of the periorbital region receptive field of the trigeminal nerve and decrease the discharges of neurons in the trigeminocervical complex. Acupuncture also reversed the abnormal skin pain response of the periorbital region receptive field of the trigeminal nerve caused by lowintensity stimulation. Discussion: We believe that our study makes a significant contribution to the literature because it is the first of its kind to use GB20 to provide relief from migraine attacks and mechanical cephalic cutaneous hypersensitivity by regulating the neuronal discharge from trigeminocervical complex.

show abstract

“…NTG, as a NO donor, injected in mice can excite trigeminal nociceptors and also promote the release of CGRP from trigeminal terminals to promote sensitization of TG neurons. The release of CGRP from the central terminals of TG neurons could repetitively excite second-order neurons in the TNC where the trigeminal ganglion projects to, leading to central sensitization and the manifestation of hyperalgesia and allodynia [20]. CGRP and NO can amplify each other's activity in a reciprocal fashion throughout the trigeminovascular system,thereby maintaining central sensitization and continuous hyperalgesia.…”

Section: The Roles Of Cgrp In the Therapeutic Effects Of Bont/a On Chmentioning

confidence: 99%

Botulinum Neurotoxin A Prevents the Development of Nitroglycerin-Induced Chronic Migraine via Inhibition of CGRP and NLRP3 Inflammasomes in Mice

Tao

Niu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background This study was designed to examine the therapeutic effects of Botulinum neurotoxin A (BoNT/A) on chronic migraine and to explore the potential mechanisms by using a mouse model of chronic migraine, which was established by repeated intraperitoneal (i.p.) injection with nitroglycerin (NTG).Methods NTG-induced basal and evoked mechanical hypersensitivity were evaluated using the von Frey filament test. Before the first injection of NTG, a single facial injection of BoNT/A was administered in the supraorbital region to explore its preventive effects on the development of chronic migraine in mice. The expression of calcitonin gene-related peptide (CGRP) and synaptosomal-associated protein25 (SNAP25) in the trigeminal ganglia (TG) and the trigeminal nucleus caudalis (TNC) were detected by Western blotting and immunostaining. Results Repeated administration of NTG resulted in basal and evoked mechanical hypersensitivity in mice. Single facial BoNT/A injection prevented the development of NTG-induced mechanical hypersensitivity in mice. Western blotting results revealed that peripheral BoNT/A injection decreased the NTG-induced upregulation of expression of CGRP and SNAP25 in the TGs and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes in the TNC. Immunostaining results revealed peripheral BoNT/A injection also decreased the NTG-induced upregulation of CGRP expression in the TNC.Conclusions Thus, these results indicate that single facial injection of BoNT/A may be a preventive treatment of chronic migraine, possible due to the inhibitory effect of BoNT/A on the expression of CGRP and SNAP25 in the TGs and NLRP3 inflammasomes in the TNC.

show abstract

NR2B-Tyr phosphorylation regulates synaptic plasticity in central sensitization in a chronic migraine rat model

Cited by 59 publications

References 40 publications

Pioglitazone Attenuates Experimental Colitis-Associated Hyperalgesia through Improving the Intestinal Barrier Dysfunction

Pioglitazone Attenuates Experimental Colitis-Associated Hyperalgesia through Improving the Intestinal Barrier Dysfunction

<p>Prophylactic Electroacupuncture on the Upper Cervical Segments Decreases Neuronal Discharges of the Trigeminocervical Complex in Migraine-Affected Rats: An in vivo Extracellular Electrophysiological Experiment</p>

Botulinum Neurotoxin A Prevents the Development of Nitroglycerin-Induced Chronic Migraine via Inhibition of CGRP and NLRP3 Inflammasomes in Mice

Contact Info

Product

Resources

About