TY - JOUR
T1 - PACAP and other neuropeptide targets link chronic migraine and opioid-induced hyperalgesia in mouse models
AU - Anapindi, Krishna D.B.
AU - Yang, Ning
AU - Romanova, Elena V.
AU - Rubakhin, Stanislav S.
AU - Tipton, Alycia
AU - Dripps, Isaac
AU - Sheets, Zoie
AU - Sweedler, Jonathan V.
AU - Pradhan, Amynah A.
N1 - Funding Information:
* This project was supported by the National Institute on Drug Abuse under Award No. P30 DA018310 (J.V.S.), and DA040688 (A.A.P.). The authors declare that they have no conflicts of interest with the contents of this article. □S This article contains supplemental Figures and Tables. ‖ To whom correspondence should be addressed: Department of Psychiatry, University of Illinois at Chicago, 1601 W Taylor St. (MC 912), Chicago, IL 60612. Tel.: 312-355-1557; Fax: 312-996-7658; E-mail: [email protected].
Publisher Copyright:
© 2019 Anapindi et al.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85075959721&partnerID=8YFLogxK
U2 - 10.1074/mcp.RA119.001767
DO - 10.1074/mcp.RA119.001767
M3 - Article
C2 - 31649062
AN - SCOPUS:85075959721
SN - 1535-9476
VL - 18
SP - 2447
EP - 2458
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
IS - 12
ER -