Dataset Information

PACAP and other neuropeptide targets link chronic migraine and opioid-induced hyperalgesia in mouse models

ABSTRACT: Understanding the precise molecular mechanisms behind chronic pain disorders such as migraine and opioid induced hyperalgesia (OIH) has been a long-standing goal met with limited success. Neuropeptides, which play a vital role in several physiological processes are also hypothesized to be involved in mediating these pain mechanisms. Here we show that change in levels of several neuropeptides and neuropeptide-precursor proteins (prohormones) correlate with migraine and OIH in mice. We also identified common prohormones that are significantly changed in both migraine and OIH. These results suggest that neuropeptides have an important role in these chronic pain disorders and might be key towards unlocking their mechanisms. This knowledge could eventually be utilized in developing an effective cure for these disorders.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Migraine

SUBMITTER: Krishna Anapindi

LAB HEAD: Jonathan V. Sweedler

PROVIDER: PXD013362 | Pride | 2019-11-06

REPOSITORIES: Pride

ACCESS DATA

Publications

PACAP and Other Neuropeptide Targets Link Chronic Migraine and Opioid-induced Hyperalgesia in Mouse Models.

Anapindi Krishna D. B. KDB Yang Ning N Romanova Elena V EV Rubakhin Stanislav S SS Tipton Alycia A Dripps Isaac I Sheets Zoie Z Sweedler Jonathan V JV Pradhan Amynah A AA

Molecular & cellular proteomics : MCP 20191024 12

Chronic use of opioids can produce opioid-induced hyperalgesia (OIH), and when used to treat migraine, these drugs can result in increased pain and headache chronicity. We hypothesized that overlapping mechanisms between OIH and chronic migraine occur through neuropeptide dysregulation. Using label-free, non-biased liquid chromatography-mass spectrometry to identify and measure changes in more than 1500 neuropeptides under these two conditions, we observed only 16 neuropeptides that were altered ...[more]

PMID: 31649062

Similar Datasets

Project description:Genetic association studies, pharmacological investigations and analysis of mice-lacking individual genes have made it clear that Cocaine administration and Withdrawal have a profound impact on multiple neurotransmitter systems. The GABAergic medium spiny neurons of the nucleus accumbens (NAc) exhibit changes in the expression of genes encoding receptors for glutamate and in the signaling pathways triggered by dopamine binding to G-protein-coupled dopamine receptors. Deep sequence analysis provides a sensitive, quantitative and global analysis of the effects of Cocaine on the NAc transcriptome. RNA prepared from the NAc of adult male mice receiving daily injections of Saline or Cocaine, or Cocaine followed by a period of Withdrawal, was used for high-throughput sequence analysis. Changes were validated by quantitative polymerase chain reaction or Western blot. On the basis of pathway analysis, a preponderance of the genes affected by Cocaine and Withdrawal was involved in the cadherin, heterotrimeric G-protein and Wnt signaling pathways. Distinct subsets of cadherins and protocadherins exhibited a sustained increase or decrease in expression. Sustained down-regulation of several heterotrimeric G-protein β- and γ-subunits was observed. In addition to altered expression of receptors for small molecule neurotransmitters, neuropeptides and endocannabinoids, changes in the expression of plasma membrane transporters and vesicular neurotransmitter transporters were also observed. The effects of chronic Cocaine and Withdrawal on the expression of genes essential to cholinergic, glutamatergic, GABAergic, peptidergic and endocannabinoid signaling are as profound as their effects on dopaminergic transmission. Simultaneous targeting of multiple Withdrawal-specific changes in gene expression may facilitate development of new therapeutic approaches that are better able to prevent relapse. High-throughput sequence analysis of RNA prepared from the nucleus accumbens of adult male mice receiving daily injections of Saline or Cocaine, or Cocaine followed by a period of Withdrawal. Nucleus accumbens libraries were sequenced in nine lanes (three technical replicates per sample) on an Illumina GAIIx using a 37-cycle paired-end sequencing protocol. Replicates were analyzed for intra-sample disparity and read data from all three lanes were then merged into one composite data file per sample; intra-sample coefficient of determination, R2 ≥ 0.98. The composite file was used for subsequent analyses.

Dataset Information

PACAP and other neuropeptide targets link chronic migraine and opioid-induced hyperalgesia in mouse models

Publications

PACAP and Other Neuropeptide Targets Link Chronic Migraine and Opioid-induced Hyperalgesia in Mouse Models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure