Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats

Nishimura, Haruki; Yoshimura, Mitsuhiro; Shimizu, Makiko; Sanada, Kenya; Sonoda, Shozo; Nishimura, Kazuaki; Baba, Kazuhiko; Ikeda, Naofumi; Motojima, Yasuhito; Maruyama, Takashi; Nonaka, Yuki; Baba, Ryoko; Onaka, Tatsushi; Horishita, Takafumi; Morimoto, Hiroyuki; Yoshida, Yasuhiro; Kawasaki, Makoto; Sakai, Akinori; Muratani, Masafumi; Conway-Campbell, Becky; Lightman, Stafford L.; Ueta, Yoichi

doi:10.1038/s42003-022-03879-8

Cited by 18 publications

(17 citation statements)

References 75 publications

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“…DCZ (MedChemExpress LLC, NJ, USA) was initially dissolved in DMSO to achieve a concentration of 10 mg/mL and then further diluted in saline to a concentration of 0.1 mg/mL. The dosages of CNO and DCZ were determined based on previous studies ( Nagai et al, 2020 ; Nishimura et al, 2022 ). All solutions were adjusted to ensure a final concentration of 1% DMSO.…”

Section: Methodsmentioning

confidence: 99%

“…In our previous research, we employed CNO (1 mg/kg) to investigate the analgesic and anti-inflammatory properties of endogenous oxytocin (OXT) using OXT-hM3Dq-mCherry transgenic rats, which express hM3Dq and mCherry specifically in OXT neurons ( Nishimura et al, 2022 ). Although DCZ has shown promise in previous studies, most of them have been conducted in mice or monkeys ( Nagai et al, 2020 ; Matsumura et al, 2022 ; Perez et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Deschloroclozapine exhibits an exquisite agonistic effect at lower concentration compared to clozapine-N-oxide in hM3Dq expressing chemogenetically modified rats

Shimizu,

Yoshimura,

Baba

et al. 2023

Front. Neurosci.

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IntroductionWithin the realm of chemogenetics, a particular form of agonists targeting designer receptors exclusively activated by designer drugs (DREADDs) has emerged. Deschloroclozapine (DCZ), a recently introduced DREADDs agonist, demonstrates remarkable potency in activating targeted neurons at a lower dosage compared to clozapine-N-oxide (CNO).MethodsWe conducted a comparative analysis of the effects of subcutaneously administered CNO (1 mg/kg) and DCZ (0.1 mg/kg) in our transgenic rats expressing hM3Dq and mCherry exclusively in oxytocin (OXT) neurons.Results and DiscussionNotably, DCZ exhibited a swift and robust elevation of serum OXT, surpassing the effects of CNO, with a significant increase in the area under the curve (AUC) up to 3 hours post-administration. Comprehensive assessment of brain neuronal activity, using Fos as an indicator, revealed comparable effects between CNO and DCZ. Additionally, in a neuropathic pain model, both CNO and DCZ increased the mechanical nociceptive and thermal thresholds; however, the DCZ-treated group exhibited a significantly accelerated onset of the effects, aligning harmoniously with the observed alterations in serum OXT concentration following DCZ administration. These findings emphasize the remarkable efficacy of DCZ in rats, suggesting its equivalent or potentially superior performance to CNO at considerably lower dosages, thus positioning it as a promising contender among DREADDs agonists.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Deschloroclozapine exhibits an exquisite agonistic effect at lower concentration compared to clozapine-N-oxide in hM3Dq expressing chemogenetically modified rats

Shimizu,

Yoshimura,

Baba

et al. 2023

Front. Neurosci.

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“… 93 In a recent study, chemogenic activation of oxytocin neurons in the PVN promotes the activation of GABAergic neurons in the SDH and alleviates hyperalgesia in inflammatory pain rats. 94 Accordingly, it is highly likely that the regulation of spinal WDR neurons by PVN and the consequent analgesic effects are achieved through the descending oxytocinergic pathway mediated by GABAergic transmission.…”

Section: Wdr Neurons Regulated By Descending Pathwaysmentioning

confidence: 99%

Understanding of Spinal Wide Dynamic Range Neurons and Their Modulation on Pathological Pain

Zhang,

Zheng,

et al. 2024

JPR

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The spinal dorsal horn (SDH) transmits sensory information from the periphery to the brain. Wide dynamic range (WDR) neurons within this relay site play a critical role in modulating and integrating peripheral sensory inputs, as well as the process of central sensitization during pathological pain. This group of spinal multi-receptive neurons has attracted considerable attention in pain research due to their capabilities for encoding the location and intensity of nociception. Meanwhile, transmission, processing, and modulation of incoming afferent information in WDR neurons also establish the underlying basis for investigating the integration of acupuncture and pain signals. This review aims to provide a comprehensive examination of the distinctive features of WDR neurons and their involvement in pain. Specifically, we will examine the regulation of diverse supraspinal nuclei on these neurons and analyze their potential in elucidating the mechanisms of acupuncture analgesia.

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“…Interestingly, there is a possibility that this modulation is in fact mediated by OT. Namely, OT shows a high positive correlation with serotonin levels, in that OT, provokes the release of serotonin in several brain regions of the limbic system, including the amygdala [ 176 , 177 ]. OT also upregulates the availability of the 5-HT1A receptor [ 178 ].…”

Section: The Underlying Mechanisms For the Neuroprotective Effect Of ...mentioning

confidence: 99%

The Role of Oxytocin in Abnormal Brain Development: Effect on Glial Cells and Neuroinflammation

Knoop

Possovre

Jacquens

et al. 2022

Cells

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The neonatal period is critical for brain development and determinant for long-term brain trajectory. Yet, this time concurs with a sensitivity and risk for numerous brain injuries following perinatal complications such as preterm birth. Brain injury in premature infants leads to a complex amalgam of primary destructive diseases and secondary maturational and trophic disturbances and, as a consequence, to long-term neurocognitive and behavioral problems. Neuroinflammation is an important common factor in these complications, which contributes to the adverse effects on brain development. Mediating this inflammatory response forms a key therapeutic target in protecting the vulnerable developing brain when complications arise. The neuropeptide oxytocin (OT) plays an important role in the perinatal period, and its importance for lactation and social bonding in early life are well-recognized. Yet, novel functions of OT for the developing brain are increasingly emerging. In particular, OT seems able to modulate glial activity in neuroinflammatory states, but the exact mechanisms underlying this connection are largely unknown. The current review provides an overview of the oxytocinergic system and its early life development across rodent and human. Moreover, we cover the most up-to-date understanding of the role of OT in neonatal brain development and the potential neuroprotective effects it holds when adverse neural events arise in association with neuroinflammation. A detailed assessment of the underlying mechanisms between OT treatment and astrocyte and microglia reactivity is given, as well as a focus on the amygdala, a brain region of crucial importance for socio-emotional behavior, particularly in infants born preterm.

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Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats

Cited by 18 publications

References 75 publications

Deschloroclozapine exhibits an exquisite agonistic effect at lower concentration compared to clozapine-N-oxide in hM3Dq expressing chemogenetically modified rats

Deschloroclozapine exhibits an exquisite agonistic effect at lower concentration compared to clozapine-N-oxide in hM3Dq expressing chemogenetically modified rats

Understanding of Spinal Wide Dynamic Range Neurons and Their Modulation on Pathological Pain

The Role of Oxytocin in Abnormal Brain Development: Effect on Glial Cells and Neuroinflammation

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