The role of oxytocin, vasopressin, and their receptors at nociceptors in peripheral pain modulation

Zheng, Haiyan; Lim, Jin‐Ho; Kim, Ye‐Rin; Jung, Sang Taek; Hwang, Sun Wook

doi:10.1016/j.yfrne.2021.100942

Cited by 15 publications

(8 citation statements)

References 113 publications

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“…In this study, we demonstrated that GnRH, a central peptide hormone, can peripherally modulate nociception via receptor-dependent mechanisms in DRG neurons. A number of known peptide hormones in the CNS have been revisited recently as a peripherally acting neuropeptides, particularly on DRG neurons of which subpopulations express their own GPCRs such as corticotropin-releasing hormone receptors, somatostatin receptors, oxytocin receptors, GPR171, etc., ( Zheng et al, 2020 ; Cho et al, 2021 ; Zheng et al, 2021 ). Such versatile expression in peripheral neurons may possibly be due to the essential role of widely monitoring changes in the internal environment.…”

Section: Discussionmentioning

confidence: 99%

“…Peripheral nociceptors of dorsal root ganglia (DRG) monitor potential tissue damage and transduce and convey such information as pain signals ( Hwang and Oh, 2007 ; Dubin and Patapoutian, 2010 ). G-protein coupled receptors (GPCRs) for neurotransmitters, neurohormones, and pro- and anti-inflammatory mediators are expressed in these neurons and tune their excitability when stimulated by ligands ( Hanack et al, 2015 ; Choi et al, 2016 ; Choi and Hwang, 2016 ; Choi and Hwang, 2018 ; Cho et al, 2021 ; Zheng et al, 2021 ). Peptidergic neurohormones are considered among the important ligands playing a role in this fashion.…”

Section: Introductionmentioning

confidence: 99%

“…Peptidergic neurohormones are considered among the important ligands playing a role in this fashion. Endogenous opioids and oxytocin are the best examples that work through descending modulatory axons mainly from periaqueductal gray, rostral ventromedial medulla, and paraventricular nuclei ( Corder et al, 2018 ; Zheng et al, 2021 ). Besides such circuit-based mechanisms, the evidence for independent productions in the periphery including immune cells or nociceptors themselves and for modulatory mechanisms in paracrine and autocrine manners are currently increasing ( Pinho-Ribeiro et al, 2017 ; Zheng et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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GnRH peripherally modulates nociceptor functions, exacerbating mechanical pain

Zheng,

Kim,

Kim

et al. 2024

Front. Mol. Neurosci.

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The function of peripheral nociceptors, the neurons that relay pain signals to the brain, are frequently tuned by local and systemic modulator substances. In this context, neurohormonal effects are emerging as an important modulatory mechanism, but many aspects remain to be elucidated. Here we report that gonadotropin-releasing hormone (GnRH), a brain-specific neurohormone, can aggravate pain by acting on nociceptors in mice. GnRH and GnRHR, the receptor for GnRH, are expressed in a nociceptor subpopulation. Administration of GnRH and its analogue, localized for selectively affecting the peripheral neurons, deteriorated mechanical pain, which was reproducible in neuropathic conditions. Nociceptor function was promoted by GnRH treatment in vitro, which appears to involve specific sensory transient receptor potential ion channels. These data suggest that peripheral GnRH can positively modulate nociceptor activities in its receptor-specific manner, contributing to pain exacerbation. Our study indicates that GnRH plays an important role in neurohormonal pain modulation via a peripheral mechanism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GnRH peripherally modulates nociceptor functions, exacerbating mechanical pain

Zheng,

Kim,

Kim

et al. 2024

Front. Mol. Neurosci.

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“…The increased BBB penetration observed with the OT glycosides seems largely due to the increased stability of the lactam rings (see SI for details). In contrast, the antinociception observed with the nonglycosylated peptide 1 may be due to peripheral OT receptor stimulation by the stabilized peptide, 56 leading to antinociception, despite the poor OTR potency observed in Table 1.…”

Section: Acs Medicinalmentioning

confidence: 93%

Structure-Based Design of Glycosylated Oxytocin Analogues with Improved Selectivity and Antinociceptive Activity

Szabó

Tanguturi

Goodman

et al. 2023

ACS Med. Chem. Lett.

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Acute and chronic pain is often treated with opioids despite the negative side effects of constipation, physical dependence, respiratory depression, and overdose. The misuse of opioid analgesics has given rise to the opioid crisis/epidemic, and alternate nonaddictive analgesics are urgently needed. Oxytocin, a pituitary hormone, is an alternative to the small molecule treatments available and has been used as an analgesic as well as for the treatment and prevention of opioid use disorder (OUD). Clinical implementation is limited by its poor pharmacokinetic profile, a result of the labile disulfide bond between two cysteine residues in the native sequence. Stable brain penetrant oxytocin analogues have been synthesized by replacement of the disulfide bond with a stable lactam and glycosidation of the C-terminus. These analogues show exquisite selectivity for the oxytocin receptor and potent in vivo antinociception in mice following peripheral (i.v.) administration, supporting further study of their clinical potential.

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“…After release into the bloodstream, it is transported predominantly to kidneys and blood vessels, where it regulates physiological functions (e.g., resorption of water, vasoconstriction, …). Vasopressin has amino acid sequences and tertiary structures similar to oxytocin, probably due to the shared origin of their encoding genes [ 62 ]. In addition, it is possible that an interplay between oxytocin and vasopressin is involved in mood and stress-response regulation [ 63 ].…”

Section: Neuropeptides In Anxiety and Depressionmentioning

confidence: 99%

Anxiety and Depression: What Do We Know of Neuropeptides?

Kupcová

Danišovič

Grgac

et al. 2022

Behavioral Sciences

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In modern society, there has been a rising trend of depression and anxiety. This trend heavily impacts the population’s mental health and thus contributes significantly to morbidity and, in the worst case, to suicides. Modern medicine, with many antidepressants and anxiolytics at hand, is still unable to achieve remission in many patients. The pathophysiology of depression and anxiety is still only marginally understood, which encouraged researchers to focus on neuropeptides, as they are a vast group of signaling molecules in the nervous system. Neuropeptides are involved in the regulation of many physiological functions. Some act as neuromodulators and are often co-released with neurotransmitters that allow for reciprocal communication between the brain and the body. Most studied in the past were the antidepressant and anxiolytic effects of oxytocin, vasopressin or neuropeptide Y and S, or Substance P. However, in recent years, more and more novel neuropeptides have been added to the list, with implications for the research and development of new targets, diagnostic elements, and even therapies to treat anxiety and depressive disorders. In this review, we take a close look at all currently studied neuropeptides, their related pathways, their roles in stress adaptation, and the etiology of anxiety and depression in humans and animal models. We will focus on the latest research and information regarding these associated neuropeptides and thus picture their potential uses in the future.

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The role of oxytocin, vasopressin, and their receptors at nociceptors in peripheral pain modulation

Cited by 15 publications

References 113 publications

GnRH peripherally modulates nociceptor functions, exacerbating mechanical pain

GnRH peripherally modulates nociceptor functions, exacerbating mechanical pain

Structure-Based Design of Glycosylated Oxytocin Analogues with Improved Selectivity and Antinociceptive Activity

Anxiety and Depression: What Do We Know of Neuropeptides?

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