Analgesic effect of central relaxin receptor activation on persistent inflammatory pain in mice: behavioral and neurochemical data

Abboud, Cynthia; Brochoire, Louison; Drouet, Adèle; Hossain, Mohammed Akhter; Hleihel, Walid; Gundlach, Andrew L.; Landry, Marc

doi:10.1097/pr9.0000000000000937

Cited by 6 publications

(6 citation statements)

References 78 publications

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“…1 D , 3 ) stimuli at 4 d post-CFA. Swiss mice thresholds were consistent with those obtained in C57/Bl6 mice in another recent study ( 31 ), although they were seemingly higher in Swiss mice than in C57/Bl6 mice due to weight/size differences ( 32 ). The 6-OHDA mice exhibited a further decrease in thermal ( Fig.…”

Section: Resultssupporting

confidence: 89%

Pain hypersensitivity in a pharmacological mouse model of attention-deficit/hyperactivity disorder

Bouchatta

Aby

Sifeddine

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Clinical evidence suggests that pain hypersensitivity develops in patients with attention-deficit/hyperactivity disorder (ADHD). However, the mechanisms and neural circuits involved in these interactions remain unknown because of the paucity of studies in animal models. We previously validated a mouse model of ADHD obtained by neonatal 6-hydroxydopamine (6-OHDA) injection. Here, we have demonstrated that 6-OHDA mice exhibit a marked sensitization to thermal and mechanical stimuli, suggesting that phenotypes associated with ADHD include increased nociception. Moreover, sensitization to pathological inflammatory stimulus is amplified in 6-OHDA mice as compared to shams. In this ADHD model, spinal dorsal horn neuron hyperexcitability was observed. Furthermore, ADHD-related hyperactivity and anxiety, but not inattention and impulsivity, are worsened in persistent inflammatory conditions. By combining in vivo electrophysiology, optogenetics, and behavioral analyses, we demonstrated that anterior cingulate cortex (ACC) hyperactivity alters the ACC–posterior insula circuit and triggers changes in spinal networks that underlie nociceptive sensitization. Altogether, our results point to shared mechanisms underlying the comorbidity between ADHD and nociceptive sensitization. This interaction reinforces nociceptive sensitization and hyperactivity, suggesting that overlapping ACC circuits may be targeted to develop better treatments.

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Section: Resultssupporting

confidence: 89%

Pain hypersensitivity in a pharmacological mouse model of attention-deficit/hyperactivity disorder

Bouchatta

Aby

Sifeddine

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…These numerous effects of relaxin are consistent with the expression pattern of its cognate receptor, RXFP1 239, 245, 246 . Notably, despite some early mapping studies of RXFP1 mRNA and binding sites in several tissues including the heart and brain, 215,247,248 few studies have explored the role of relaxin/RXFP1 signaling in brain function 249–252 …”

Section: Insulin‐like (Relaxin)‐family Peptide and Receptor Systemsmentioning

confidence: 68%

“…239,245,246 Notably, despite some early mapping studies of RXFP1 mRNA and binding sites in several tissues including the heart and brain, 215,247,248 few studies have explored the role of relaxin/RXFP1 signaling in brain function. [249][250][251][252] The INSL3/RXFP2 system was initially identified as having a clear role in male reproduction, specifically in the development of the gubernaculum and testicular descent, because INSL3 is highly expressed in testicular Leydig cells in animals and human 253 and both…”

Section: Recent Advances and Current Anatomical And Functional Knowledgementioning

confidence: 99%

“…215 Notably, recent surveys of the transcriptome of mouse and human brain has identified putative relaxin/RXFP1 circuits within cerebral cortex that warrant further investigation. 300,301 Indeed, in a recent study, central administration of relaxin and a RXFP1-selective peptide, analogue, relaxin B7-33, produced an acute analgesic action in a mouse model of inflammatory pain, 251 and further studies should reveal the regional sites and mechanisms of action. Furthermore, in light of these findings, the effect of relaxin/RXFP1 signaling on other central modalities should be explored.…”

Section: Current Neurochemical-anatomicalfunctional Knowledge Gaps An...mentioning

confidence: 99%

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History of key regulatory peptide systems and perspectives for future research

Chen

Rehfeld

Watts

et al. 2023

J Neuroendocrinology

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Throughout the 20th Century, regulatory peptide discovery advanced from the identification of gut hormones to the extraction and characterization of hypothalamic hypophysiotropic factors, and to the isolation and cloning of multiple brain neuropeptides. These discoveries were followed by the discovery of G‐protein‐coupled and other membrane receptors for these peptides. Subsequently, the systems physiology associated with some of these multiple regulatory peptides and receptors has been comprehensively elucidated and has led to improved therapeutics and diagnostics and their approval by the US Food and Drug Administration. In light of this wealth of information and further potential, it is truly a time of renaissance for regulatory peptides. In this perspective, we review what we have learned from the pioneers in exemplified fields of gut peptides, such as cholecystokinin, enterochromaffin‐like‐cell peptides, and glucagon, from the trailblazing studies on the key stress hormone, corticotropin‐releasing factor, as well as from more recently characterized relaxin‐family peptides and receptors. The historical viewpoints are based on our understanding of these topics in light of the earliest phases of research and on subsequent studies and the evolution of knowledge, aiming to sharpen our vision of the current state‐of‐the‐art and those studies that should be prioritized in the future.

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“…However, we observed that several genes exhibited noticeable batch-related variance, though it tended to be smaller in magnitude compared to cell-type variance ( Supplementary Figure 3A ). To begin, we analyzed the effect of Crescendo on three genes that were cell-type specific: Gpr34 in microglia cells 40,41 , Rxfp1 42,43 in cortical excitatory neurons, and Epha8 44 in striatal inhibitory neurons. Each of these genes were subject to technical effects ( Figure 2D, 2G , Supplementary Figure 4A-E ).…”

Section: Resultsmentioning

confidence: 99%

Integrating spatial transcriptomics count data with Crescendo improves visualization and detection of spatial gene patterns

Millard,

Chen,

Palshikar

et al. 2024

Preprint

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Spatial transcriptomics allows for the analysis of a cell's gene expression in the context of its physical location. With spatial transcriptomics data, investigators often want to find genes of interest whose spatial patterns are biologically relevant in multiple samples. However, due to confounding factors in spatial data that produce noise across samples, datasets, and technologies, it is challenging to visualize genes and their spatial patterns across samples. We present Crescendo, an integration algorithm that performs correction directly on gene expression counts to reduce variation from technical confounders. We first apply Crescendo to a 3-sample spatial transcriptomics mouse brain dataset to show how Crescendo enables accurate visualization of gene expression across these spatial transcriptomic samples. We then demonstrate Crescendo's scalability by integrating a 16-sample immuno-oncology dataset of 7 million cells. Finally, we show that Crescendo can perform cross-technology integration by merging a colorectal cancer (CRC) scRNA-seq dataset with two CRC spatial transcriptomics samples. By transferring information between technologies, Crescendo can impute poorly expressed genes to improve detection of gene-gene colocalization, such as ligand-receptor interactions.

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Analgesic effect of central relaxin receptor activation on persistent inflammatory pain in mice: behavioral and neurochemical data

Abstract: Supplemental Digital Content is Available in the Text. Relaxin peptide analogues produce strong but transient analgesia in inflammatory pain in mouse. Relaxin and its RXFP1 receptor represent a new peptidergic system that modulates pain processing in the forebrain areas.

Cited by 6 publications

References 78 publications

Pain hypersensitivity in a pharmacological mouse model of attention-deficit/hyperactivity disorder

Pain hypersensitivity in a pharmacological mouse model of attention-deficit/hyperactivity disorder

History of key regulatory peptide systems and perspectives for future research

Integrating spatial transcriptomics count data with Crescendo improves visualization and detection of spatial gene patterns

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