A possible correlation between oxytocin-induced and angiotensin IV-induced anti-hyperalgesia at the spinal level in rats

Chow, Lok-Hi; Tao, Pao‐Luh; Chen, Jin-Chung; Liao, Ruey-Ming; Chang, En-Pei; Huang, Eagle Yi‐Kung

doi:10.1016/j.peptides.2012.10.012

Cited by 15 publications

(15 citation statements)

References 46 publications

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“…Although peripheral OT has also been reported to function in anti-inflammation [ 21 ], in a previous study, we focused on the effect of OT at the spinal level [ 22 ]. We demonstrated that i.t.…”

Section: Introductionmentioning

confidence: 99%

“…We demonstrated that i.t. administration of OT produced a marked anti-hyperalgesic effect in male rats with carrageenan-induced inflammatory hyperalgesia [ 22 ]. However, the oxytocinergic system has been demonstrated to exhibit sexual dimorphism in the brain, which may cause differences in behavioral expression (e.g., social behavior) [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…We also investigated the potential effect of PVN stimulation on hyperalgesia in female rats. The PVN-stimulation model is well established and widely used [ 22 ]. Thus, the results of our experiments could verify the possible function of the descending OT pathway in anti-hyperalgesia in female rats.…”

Section: Introductionmentioning

confidence: 99%

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Sex Difference in Oxytocin-Induced Anti-Hyperalgesia at the Spinal Level in Rats with Intraplantar Carrageenan-Induced Inflammation

Chow

Chen

et al. 2016

PLoS ONE

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Previously, we demonstrated intrathecal administration of oxytocin strongly induced anti-hyperalgesia in male rats. By using an oxytocin-receptor antagonist (atosiban), the descending oxytocinergic pathway was found to regulate inflammatory hyperalgesia in our previous study using male rats. The activity of this neural pathway is elevated during hyperalgesia, but whether this effect differs in a sex-dependent manner remains unknown. We conducted plantar tests on adult male and female virgin rats in which paw inflammation was induced using carrageenan. Exogenous (i.t.) application of oxytocin exerted no anti-hyperalgesic effect in female rats, except at an extremely high dose. Female rats exhibited similar extent of hyperalgesia to male rats did when the animals received the same dose of carrageenan. When atosiban was administered alone, the severity of hyperalgesia was not increased in female rats. Moreover, insulin-regulated aminopeptidase (IRAP) was expressed at higher levels in the spinal cords of female rats compared with those of male rats. Oxytocin-induced anti-hyperalgesia exhibits a sex-dependent difference in rats. This difference can partially result from the higher expression of IRAP in the spinal cords of female rats, because IRAP functions as an enzyme that degrades oxytocin. Our study confirms the existence of a sex difference in oxytocin-induced anti-hyperalgesia at the spinal level in rats.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sex Difference in Oxytocin-Induced Anti-Hyperalgesia at the Spinal Level in Rats with Intraplantar Carrageenan-Induced Inflammation

Chow

Chen

et al. 2016

PLoS ONE

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“…For example, centrally administered Ang IV (0.1–1 μg/mouse) provides protection against pentylenetetrazol (PTZ)-induced seizures in mice, by dose-dependently increasing PTZ-seizure threshold and decreasing PTZ-seizure intensity ( Tchekalarova et al, 2001 ). Additionally, inhibition of IRAP by Ang IV has an anxiolytic ( Beyer et al, 2010 ) and anti-hyperalgesia ( Chow et al, 2013 ) effect in rats and an anti-allodynia effect in male mice ( Chow et al, 2018 ), all proposed to be due to elevated levels of oxytocin in the brain or spinal cord.…”

Section: Targeting the C-terminal Domain Of Irapmentioning

confidence: 99%

Is There an Interplay Between the Functional Domains of IRAP?

Vear

Gaspari

Thompson

et al. 2020

Front. Cell Dev. Biol.

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As a member of the M1 family of aminopeptidases, insulin regulated aminopeptidase (IRAP) is characterized by distinct binding motifs at the active site in the C-terminal domain that mediate the catalysis of peptide substrates. However, what makes IRAP unique in this family of enzymes is that it also possesses trafficking motifs at the N-terminal domain which regulate the movement of IRAP within different intracellular compartments. Research on the role of IRAP has focused predominantly on the C-terminus catalytic domain in different physiological and pathophysiological states ranging from pregnancy to memory loss. Many of these studies have utilized IRAP inhibitors, that bind competitively to the active site of IRAP, to explore the functional significance of its catalytic activity. However, it is unknown whether these inhibitors are able to access intracellular sites where IRAP is predominantly located in a basal state as the enzyme may need to be at the cell surface for the inhibitors to mediate their effects. This property of IRAP has often been overlooked. Interestingly, in some pathophysiological states, the distribution of IRAP is altered. This, together with the fact that IRAP possesses trafficking motifs, suggest the localization of IRAP may play an important role in defining its physiological or pathological functions and provide insights into the interplay between the two functional domains of the protein.

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“…OXY administered systemically or at CNS sites such as the spinal intrathecal space [112], PAG [53,54], caudate nucleus [113], nucleus accumbens [114] and amygdala [115] produces analgesia in rodents. Specifically, studies examining the effects of OXY administration have shown rats to be less sensitive to electrical, thermal, chemical and mechanical pain stimuli [49, 116–125], and to also have less pain following acute stress [75], acute inflammation [50,112,126–129], tooth pulp stimulation [108, 109, 130] and neuropathic injury [131,132]. In most cases, this analgesia was reversed with OXTR antagonists.…”

Section: Oxytocin Inhibits Somatic Nociceptionmentioning

confidence: 99%

Oxytocin - A Multifunctional Analgesic for Chronic Deep Tissue Pain

Goodin

Ness²,

Robbins³

2014

CPD

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The treatment of chronic pain arising from deep tissues is currently inadequate and there is need for new pharmacological agents to provide analgesia. The endogenous paracrine hormone/neurotransmitter oxytocin is intimately involved in the modulation of multiple physiological and psychological functions. Recent experiments have given clear evidence for a role of oxytocin in the modulation of nociception. The present article reviews the existent human and basic science data related to the direct and indirect effects of oxytocin on pain. Due to its analgesic, anxiolytic, antidepressant and other central nervous system effects, there is strong evidence that oxytocin and other drugs acting through the oxytocin receptor could act as multifunctional analgesics with unique therapeutic value.

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A possible correlation between oxytocin-induced and angiotensin IV-induced anti-hyperalgesia at the spinal level in rats

Cited by 15 publications

References 46 publications

Sex Difference in Oxytocin-Induced Anti-Hyperalgesia at the Spinal Level in Rats with Intraplantar Carrageenan-Induced Inflammation

Sex Difference in Oxytocin-Induced Anti-Hyperalgesia at the Spinal Level in Rats with Intraplantar Carrageenan-Induced Inflammation

Is There an Interplay Between the Functional Domains of IRAP?

Oxytocin - A Multifunctional Analgesic for Chronic Deep Tissue Pain

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