Activation of Spinal Glucagon-Like Peptide-1 Receptors Specifically Suppresses Pain Hypersensitivity

Gong, Nian; Xiao, Qi; Zhu, Bingquan; Zhang, Chang-Yue; Wang, Yanchao; Fan, Hui; Ma, Aiqun; Wang, Yongxiang

doi:10.1523/jneurosci.4703-13.2014

Cited by 115 publications

(151 citation statements)

References 68 publications

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“…It has been established that spinal cord microglial cells play a crucial role in neuropathic pain by releasing mediators that activate nociceptive neurons [90]. However, they can also be a source of β -END and release it in response to diverse stimuli, such as corticotrophin-releasing hormone (CRH) or noradrenaline stimulation [91], and upon glucagon-like peptide-1 (GLP-1) receptor activation [92]. Induction of β -END by a GLP-1 receptor agonist was found to be mediated by a p38 MAPK-dependent mechanism in spinal dorsal horn microglia [93].…”

Section: Pomc-derived Peptidesmentioning

confidence: 99%

“…Induction of β -END by a GLP-1 receptor agonist was found to be mediated by a p38 MAPK-dependent mechanism in spinal dorsal horn microglia [93]. Microglial β -END, in turn, mediates GLP-1 antinociceptive effects in pain hypersensitivity states by activating opioid receptors located on neurons [92]. In addition, β -END (and other opioid receptor ligands) may act directly on microglia, although little is known about direct effects of β -END on these cells.…”

Section: Pomc-derived Peptidesmentioning

confidence: 99%

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Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

Carniglia

Ramírez

Durand

et al. 2017

Mediators of Inflammation

183

129

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Microglial cells are responsible for immune surveillance within the CNS. They respond to noxious stimuli by releasing inflammatory mediators and mounting an effective inflammatory response. This is followed by release of anti-inflammatory mediators and resolution of the inflammatory response. Alterations to this delicate process may lead to tissue damage, neuroinflammation, and neurodegeneration. Chronic pain, such as inflammatory or neuropathic pain, is accompanied by neuroimmune activation, and the role of glial cells in the initiation and maintenance of chronic pain has been the subject of increasing research over the last two decades. Neuropeptides are small amino acidic molecules with the ability to regulate neuronal activity and thereby affect various functions such as thermoregulation, reproductive behavior, food and water intake, and circadian rhythms. Neuropeptides can also affect inflammatory responses and pain sensitivity by modulating the activity of glial cells. The last decade has witnessed growing interest in the study of microglial activation and its modulation by neuropeptides in the hope of developing new therapeutics for treating neurodegenerative diseases and chronic pain. This review summarizes the current literature on the way in which several neuropeptides modulate microglial activity and response to tissue damage and how this modulation may affect pain sensitivity.

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Section: Pomc-derived Peptidesmentioning

confidence: 99%

Section: Pomc-derived Peptidesmentioning

confidence: 99%

Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

Carniglia

Ramírez

Durand

et al. 2017

Mediators of Inflammation

183

129

View full text Add to dashboard Cite

show abstract

“…In agreement with these results, we showed that female rats reduced GLP-1 hormone expression after the Zymosan injection. It was reported that GLP-1 hormone had an antinociceptive effect in formalin injected male rats [11,24]. This effect was related with the modulation of opioidergic system [25].…”

Section: Discussionmentioning

confidence: 99%

“…This process involves spinal microglia and astrocytes release of pro and anti-inflammatory mediators [10]. Hence, a recent study has shown that microglial activation has a potent antinociceptive activity by a mechanism that involves the intestinal hormone Glucagon-like peptide-1 (GLP-1) receptor [11]. The activation of GLP-1R promotes the release of anti-inflammatory Interleukin 10 and β-endorphins at the spinal circuit [11].…”

Section: Introductionmentioning

confidence: 99%

Sex differences in central inflammatory pain sensitization are associated with differential expression of glycine receptors and GLP-1 at the spinal cord

Mariqueo

Amestica

Pino

et al. 2020

Preprint

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BackgroundFemales have higher inflammatory pain representation. However, sex differences in central pain sensitization and the regulation of nociceptive response to peripheral inflammation remain unclear. The central pain sensitization is mediated by inhibitory neurotransmission and glial cell activity dysregulation where spinal glycine and GLP-1 receptors have described play a critical role.ObjectivesThe aim of this study was to compare the mechanical withdrawal nociceptive threshold with spinal glycine receptor subunits and GLP-1 expression in adult male and female rats after inflammatory hypersensitivity.MethodsSex differences in inflammatory nociception were evaluated before and after intraplantar hindpaw Zymosan A injection in Sprague-Dawley rats. Mechanical paw withdrawal thresholds were tested using von Frey filaments.Western blot was used to measure GlyRs subunits protein levels in the spinal cord. GLP-1 was determined using the Magnetic Luminex Assay.ResultsA reduced nociceptive threshold was observed in males and females rats after 4 hours of inflammatory Zymosan A injection. However, this reduction was significantly major in females. Western blot analysis demonstrated significantly increased α1, α2, α3 and β GlyR subunit levels in male rats. Female rats only increased α3 and β GlyR subunits after Zymosan A injection. GLP-1 was reduced in female spinal tissues after an inflammatory injury.ConclusionsOur study indicates that sex differences in nociceptive threshold after inflammatory Zymosan A rat pain sensitization is related to the sex differences in glycine receptor subunits and GLP-1 expression at the spinal cord.

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“…Streptozotosin ile diyabet oluşturulan farelerde GLP-1 analoglarının sinir azalmış sinir ileti hızı ve hipoaljeziyi azaltılırken ve nörit büyümesinin arttığı gözlenmiştir (27). Periferik sinir harabiyeti sonrasında medulla spinalisde GLP-1 reseptör sayısının arttığı da saptanmıştır (28). …”

Section: Glp-1 Ve Glp-1 Reseptör Agonsitlerinin Gıda Alımı Veunclassified

The Effects of Glucagon Like Peptid-1 on Nervous System and Appetite

Özaçmak¹,

Bayraktaroğlu²

2017

Turk J Diab Obes

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ÖZET ABSTRACTGlucagon-like peptide-1(GLP-1) is a gut hormone secreted from L cells of the small intestine in response to food ingestion, and facilitates glucose-dependent insülin secretion. GLP-1 is also a neurotransmitter synthesized by a small population of neurons in the nucleus of the solitary tract in the caudal brainstem. Currently, the GLP-1 receptor agonists exendin-4, liraglutide and lixisenatide are approved for treatment of Type 2 diabetes mellitus (T2DM). The distribution of GLP-1 receptors in the brain suggests they play a central role in the regulation of neuronal activity and protect the brain tissue. Several studies have demonstrated the therapeutic effect of GLP-1 analog on animal models of Alzheimer disease, Parkinson disease and stroke. GLP-1 acts as a growth factor in the brain, and has been shown to induce neurite outgrowth and to protect against oxidative stress and reduces apoptosis. GLP-1 receptor agonists that cross the bloodbrain barrier can directly impact brain function independent of vagal afferent stimulation. It is clear that the central GLP-1 system plays a role in the regulation of food intake. Increasing evidence shows that central or peripheral GLP-1 administration reduces food intake in rodents and man. Furthermore, because of the suppression of appetite also induced by GLP-1 and the subsequent bodyweight loss in response to the prolonged administration of the peptide, GLP-1-derivative drugs have also been approved for the treatment of obesity. In this review, the neuroprotective effects of GLP-1 in the nervous system and central effects on appetite were discussed.

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Activation of Spinal Glucagon-Like Peptide-1 Receptors Specifically Suppresses Pain Hypersensitivity

Cited by 115 publications

References 68 publications

Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

Sex differences in central inflammatory pain sensitization are associated with differential expression of glycine receptors and GLP-1 at the spinal cord

The Effects of Glucagon Like Peptid-1 on Nervous System and Appetite

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