scholarly journals Microbiota regulates visceral pain in the mouse

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Pauline Luczynski ◽  
Monica Tramullas ◽  
Maria Viola ◽  
Fergus Shanahan ◽  
Gerard Clarke ◽  
...  

The perception of visceral pain is a complex process involving the spinal cord and higher order brain structures. Increasing evidence implicates the gut microbiota as a key regulator of brain and behavior, yet it remains to be determined if gut bacteria play a role in visceral sensitivity. We used germ-free mice (GF) to assess visceral sensitivity, spinal cord gene expression and pain-related brain structures. GF mice displayed visceral hypersensitivity accompanied by increases in Toll-like receptor and cytokine gene expression in the spinal cord, which were normalized by postnatal colonization with microbiota from conventionally colonized (CC). In GF mice, the volumes of the anterior cingulate cortex (ACC) and periaqueductal grey, areas involved in pain processing, were decreased and enlarged, respectively, and dendritic changes in the ACC were evident. These findings indicate that the gut microbiota is required for the normal visceral pain sensation.

2021 ◽  
Vol 33 (3) ◽  
Author(s):  
Lars Wilmes ◽  
James M. Collins ◽  
Kenneth J. O'Riordan ◽  
Siobhain M. O’Mahony ◽  
John F. Cryan ◽  
...  

2019 ◽  
Vol 117 (38) ◽  
pp. 23311-23316 ◽  
Author(s):  
Julia M. George ◽  
Zachary W. Bell ◽  
Daniel Condliffe ◽  
Kirstin Dohrer ◽  
Teresa Abaurrea ◽  
...  

Prolonged social isolation has negative effects on brain and behavior in humans and other social organisms, but neural mechanisms leading to these effects are not understood. Here we tested the hypothesis that even brief periods of social isolation can alter gene expression and DNA methylation in higher cognitive centers of the brain, focusing on the auditory/associative forebrain of the highly social zebra finch. Using RNA sequencing, we first identified genes that individually increase or decrease expression after isolation and observed general repression of gene sets annotated for neurotrophin pathways and axonal guidance functions. We then pursued 4 genes of large effect size: EGR1 and BDNF (decreased by isolation) and FKBP5 and UTS2B (increased). By in situ hybridization, each gene responded in different cell subsets, arguing against a single cellular mechanism. To test whether effects were specific to the social component of the isolation experience, we compared gene expression in birds isolated either alone or with a single familiar partner. Partner inclusion ameliorated the effect of solo isolation on EGR1 and BDNF, but not on FKBP5 and UTS2B nor on circulating corticosterone. By bisulfite sequencing analysis of auditory forebrain DNA, isolation caused changes in methylation of a subset of differentially expressed genes, including BDNF. Thus, social isolation has rapid consequences on gene activity in a higher integrative center of the brain, triggering epigenetic mechanisms that may influence processing of ongoing experience.


2003 ◽  
Vol 184 (1) ◽  
pp. 313-325 ◽  
Author(s):  
Masaya Nakamura ◽  
Richard A Houghtling ◽  
Linda MacArthur ◽  
Barbara M Bayer ◽  
Barbara S Bregman

2016 ◽  
Vol 19 (8) ◽  
pp. pyw020 ◽  
Author(s):  
Pauline Luczynski ◽  
Karen-Anne McVey Neufeld ◽  
Clara Seira Oriach ◽  
Gerard Clarke ◽  
Timothy G. Dinan ◽  
...  

Author(s):  
Songxue Su ◽  
Mengqi Li ◽  
Di Wu ◽  
Jing Cao ◽  
Xiuhua Ren ◽  
...  

Chronic neuropathic pain caused by nerve damage is a most common clinical symptom, often accompanied by anxiety- and depression-like symptoms. Current treatments are very limited at least in part due to incompletely understanding mechanisms underlying this disorder. Changes in gene expression in the dorsal root ganglion (DRG) have been acknowledged to implicate in neuropathic pain genesis, but how peripheral nerve injury alters the gene expression in other pain-associated regions remains elusive. The present study carried out strand-specific next-generation RNA sequencing with a higher sequencing depth and observed the changes in whole transcriptomes in the spinal cord (SC), anterior cingulate cortex (ACC), and amygdala (AMY) following unilateral fourth lumbar spinal nerve ligation (SNL). In addition to providing novel transcriptome profiles of long non-coding RNAs (lncRNAs) and mRNAs, we identified pain- and emotion-related differentially expressed genes (DEGs) and revealed that numbers of these DEGs displayed a high correlation to neuroinflammation and apoptosis. Consistently, functional analyses showed that the most significant enriched biological processes of the upregulated mRNAs were involved in the immune system process, apoptotic process, defense response, inflammation response, and sensory perception of pain across three regions. Moreover, the comparisons of pain-, anxiety-, and depression-related DEGs among three regions present a particular molecular map among the spinal cord and supraspinal structures and indicate the region-dependent and region-independent alterations of gene expression after nerve injury. Our study provides a resource for gene transcript expression patterns in three distinct pain-related regions after peripheral nerve injury. Our findings suggest that neuroinflammation and apoptosis are important pathogenic mechanisms underlying neuropathic pain and that some DEGs might be promising therapeutic targets.


2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Dana Tilley ◽  
Ricardo Vallejo ◽  
Ramsin Benyamin ◽  
Laura Vogel ◽  
Jeffery Kramer

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