scholarly journals Spared nerve injury causes sexually dimorphic mechanical allodynia and differential gene expression in spinal cords and dorsal root ganglia in rats

2020 ◽  
Author(s):  
Fredrik H.G. Ahlström ◽  
Kert Mätlik ◽  
Hanna Viisanen ◽  
Kim B. Blomkvist ◽  
Xiaonan Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Nerve Injury ◽  
Differential Gene Expression ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Sexually Dimorphic ◽  
Spared Nerve Injury ◽  
Cell Counts ◽  
Differential Gene

Abstract BACKGROUND Neuropathic pain (NP) is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. Using the spared nerve injury (SNI) model in rats, we characterized sex differences in behaviour, analysed dorsal root ganglion (DRG) and spinal cord (SC) tissues with transcriptomics and immunohistochemistry assays, and examined the proteome of cerebrospinal fluid (CSF). METHODS The study comprised two experiments, with male and female Sprague-Dawley rats subjected to SNI- and sham-surgeries. Mechanical and cold allodynias were assessed using von Frey filaments and the acetone test, respectively. Samples were extracted on Day 21 for CSF proteome and DRG and SC analysis for neuronal markers (IB4 and CGRP) and glial cell markers (IBA1 and GFAP), respectively, in Experiment I. Lumbar 4-5 DRGs and SC segments were collected for RNA-seq analysis on Day 7 in Experiment II. Differential gene expression in DRG and SC was calculated using DESeq2, and pathway analyses were conducted using iPathwayguide. RESULTS Females developed stronger mechanical allodynia in both experiments. Equivalent decreases in CGRP and IB-4 positive cell counts in DRG and increases in glial cells markers in the SC were seen in both sexes. No CSF protein showed change following SNI in any group. RNASeq of DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). Analyses of biological processes revealed differences in T and B cell functions in DRG and neuronal processes in both DRG and SC. CONCLUSIONS We observed significantly stronger mechanical allodynia in females and many sexually dimorphic changes in gene expression, following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP and underline the importance of investigating NP in both sexes.

scholarly journals Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats

2021 ◽  
Author(s):  
F.H.G. Ahlström ◽  
K. Mätlik ◽  
H. Viisanen ◽  
K.J. Blomqvist ◽  
X. Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Nerve Injury ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Female Rats ◽  
Sexually Dimorphic ◽  
Spared Nerve Injury ◽  
Rna Seq

AbstractNeuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.

Differential gene expression changes in the dorsal root versus trigeminal ganglia following peripheral nerve injury in rats

2020 ◽  
Vol 24 (5) ◽  
pp. 967-982 ◽  
Author(s):  
Olga A. Korczeniewska ◽  
Giannina Katzmann Rider ◽  
Sheetal Gajra ◽  
Vivek Narra ◽  
Vaishnavi Ramavajla ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Differential Gene Expression ◽  
Peripheral Nerve Injury ◽  
Dorsal Root ◽  
Trigeminal Ganglia ◽  
Differential Gene

scholarly journals DNA Microarray Analysis of Differential Gene Expression in the Dorsal Root Ganglia of Four Different Neuropathic Pain Mouse Models

2020 ◽  
Vol Volume 13 ◽  
pp. 3031-3043
Author(s):  
Hiroyuki Yokoyama ◽  
Takashi Hirai ◽  
Tetsuya Nagata ◽  
Mitsuhiro Enomoto ◽  
Hidetoshi Kaburagi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neuropathic Pain ◽  
Mouse Models ◽  
Differential Gene Expression ◽  
Microarray Analysis ◽  
Dna Microarray ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Dna Microarray Analysis ◽  
Differential Gene

scholarly journals Pulsed Radiofrequency Modulates Pain Regulatory Gene Expression Along the Nociceptive Pathway

2013 ◽  
Vol 5;16 (5;9) ◽  
pp. E601-E613
Author(s):  
Ricardo Vallejo
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Mechanical Allodynia ◽  
Spared Nerve Injury ◽  
Pulsed Radiofrequency ◽  
Sprague Dawley ◽  
Tnf Α ◽  
Nociceptive Pathway

Background: Pulsed radiofrequency (PRF) therapy is a clinical treatment utilizing electromagnetic energy aimed to relieve neuropathic pain. This is the first study examining the modulated expression of pain regulatory genes following the induction of the spared nerve injury (SNI) pain model and subsequently treated with PRF therapy. Objectives: The present study investigated the behavioral efficacy of PRF therapy in rats exhibiting sciatic nerve injury and examined gene expression changes in the sciatic nerve, ipsilateral L5 dorsal root ganglia (DRG), and spinal cord. Study Design: A randomized, experimental trial. Setting: Department of Biological Sciences, Illinois State University and Department of Psychology, Illinois Wesleyan University. Methods: An SNI model was used in male Sprague-Dawley rats (weight 260-310 g). A sham surgery was also performed as a control group. After 3 days development of the SNI model, an RF electrode was applied to the sciatic nerve proximal to the site of injury and stimulated for 3 minutes. The response to mechanical stimuli was assessed throughout the duration of the study. Furthermore, changes in gene expression along the nociceptive tract (sciatic nerve, DRG, and spinal cord) were assessed 24 hours post-PRF therapy. Results: It was observed that the mechanical allodynia, induced by SNI model, was reversed to control values within 24 hours post-PRF therapy. Additionally, modulated expression of pain regulatory genes was observed after induction of the SNI model. Following PRF therapy, expression of many of these genes returned to control values (sham) in each of the tissues tested. Increased proinflammatory gene expression, such as TNF-α and IL-6, observed in the sciatic nerve (site of injury) in the SNI group was returned to baseline values following PRF therapy. Up-regulation of GABAB-R1, Na/K ATPase, and 5-HT3r as well as down regulation of TNF-α and IL-6 were also observed in the DRG in the SNI-PRF group relative to the SNI group. Up-regulation of Na/K ATPase and c-Fos was found in the spinal cord following PRF treatment relative to the SNI group. Limitations: Immediate changes in gene expression were observed at 24 hours to better determine the mechanism with no long-term data at this time. Protein expression was not assessed in addition to gene expression changes. Conclusion: These results indicate that the electromagnetic energy applied via PRF therapy influences the reversal of behavioral and molecular effects of hypersensitivity developed from a peripheral nerve injury. Key words: Pulsed radiofrequency, PRF; spared nerve injury, SNI; electromagnetic stimulation; Sprague-Dawley, rat; withdrawal threshold; mechanical allodynia, Von Frey; gene expression; nociceptive pathway; electroneuromodulation; cytokines

scholarly journals Assessment of differential gene expression in human peripheral nerve injury

BMC Genomics ◽  
2002 ◽  
Vol 3 (1) ◽  
Author(s):  
Yuanyuan Xiao ◽  
Mark R Segal ◽  
Douglas Rabert ◽  
Andrew H Ahn ◽  
Praveen Anand ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Differential Gene Expression ◽  
Peripheral Nerve Injury ◽  
Differential Gene

scholarly journals Differential gene expression and alternative splicing of survivin following mouse sciatic nerve injury

Spinal Cord ◽  
2009 ◽  
Vol 47 (10) ◽  
pp. 739-744 ◽  
Author(s):  
S Amiri ◽  
M Movahedin ◽  
S J Mowla ◽  
Z Hajebrahimi ◽  
M Tavallaei
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Differential Gene Expression ◽  
Sciatic Nerve Injury ◽  
Differential Gene
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