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

Krishna D.B. Anapindi, Ning Yang, Elena V. Romanova, Stanislav S. Rubakhin, Alycia Tipton, Isaac Dripps, Zoie Sheets, Jonathan V. Sweedler, Amynah A. Pradhan

Research output: Contribution to journalArticle

Abstract

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 between the two conditions. The known pro-migraine molecule, calcitonin-gene related peptide, was among seven peptides associated with chronic migraine, with several pain-processing neuropeptides among the nine other peptides affected in OIH. Further, composite peptide complements Pituitary adenylate cyclase- activating polypeptide (PACAP), Vasoactive intestinal peptide (VIP) and Secretogranin (SCG) showed significant changes in both chronic migraine and OIH. In a follow-up pharmacological study, we confirmed the role of PACAP in models of these two disorders, validating the effectiveness of our peptidomic approach, and identifying PACAP as a mechanistic link between chronic migraine and OIH. Data are available via ProteomeXchange with identifier PXD013362.

Original languageEnglish (US)
Pages (from-to)2447-2458
Number of pages12
JournalMolecular and Cellular Proteomics
Volume18
Issue number12
DOIs
StatePublished - Jan 1 2019

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Pituitary Adenylate Cyclase-Activating Polypeptide
Hyperalgesia
Neuropeptides
Migraine Disorders
Opioid Analgesics
Peptides
Chromogranins
Pain
Calcitonin Gene-Related Peptide
Vasoactive Intestinal Peptide
Liquid chromatography
Liquid Chromatography
Mass spectrometry
Headache
Labels
Mass Spectrometry
Pharmacology
Molecules
Composite materials
Processing

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Cite this

PACAP and other neuropeptide targets link chronic migraine and opioid-induced hyperalgesia in mouse models. / Anapindi, Krishna D.B.; Yang, Ning; Romanova, Elena V.; Rubakhin, Stanislav S.; Tipton, Alycia; Dripps, Isaac; Sheets, Zoie; Sweedler, Jonathan V.; Pradhan, Amynah A.

In: Molecular and Cellular Proteomics, Vol. 18, No. 12, 01.01.2019, p. 2447-2458.

Research output: Contribution to journalArticle

Anapindi, Krishna D.B. ; Yang, Ning ; Romanova, Elena V. ; Rubakhin, Stanislav S. ; Tipton, Alycia ; Dripps, Isaac ; Sheets, Zoie ; Sweedler, Jonathan V. ; Pradhan, Amynah A. / PACAP and other neuropeptide targets link chronic migraine and opioid-induced hyperalgesia in mouse models. In: Molecular and Cellular Proteomics. 2019 ; Vol. 18, No. 12. pp. 2447-2458.
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