PMID- 29430557
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2452-073X (Print)
IS  - 2452-073X (Electronic)
IS  - 2452-073X (Linking)
VI  - 1
DP  - 2017 Jan-Jul
TI  - Environmental Toxin Acrolein Alters Levels of Endogenous Lipids, Including TRP 
      Agonists: A Potential Mechanism for Headache Driven by TRPA1 Activation.
PG  - 28-36
LID - 10.1016/j.ynpai.2017.03.001 [doi]
AB  - Exposure to airborne toxins can trigger headaches, but the mechanisms are not 
      well understood. Some environmental toxins, such as acrolein, activate transient 
      receptor potential ankyrin 1 (TRPA1), a receptor involved in pain sensation that 
      is highly expressed in the trigeminovascular system. It has been shown in rat 
      models that repeated exposure to acrolein induces trigeminovascular sensitization 
      to both TRPA1 and TRP vanilloid 1 (TRPV1) agonists, a phenomenon linked to 
      headache. In this study, we test the hypothesis that the sensitization of 
      trigeminovascular responses in rats after acrolein exposure via inhalation is 
      associated with changes in levels of endogenous lipids, including TRPV1 agonists, 
      in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics 
      analysis of 80 lipids was performed on each tissue after acute acrolein, chronic 
      acrolein, or room air control. Both acute and chronic acrolein exposure drove 
      widespread alterations in lipid levels. After chronic acrolein exposure, levels 
      of all 6 N-acyl ethanolamines in the screening library, including the endogenous 
      cannabinoid and TRPV1 agonist, N-arachidonoyl ethanolamine, were elevated in 
      trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by 
      acrolein exposure may indicate further downstream signaling, in that we also show 
      here that a combination of these TRPV1 endogenous agonists increases the potency 
      of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 
      agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and 
      down regulated after acrolein exposure. These data support the hypothesis that 
      lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 
      agonist and environmental toxin, acrolein, drives trigeminovascular 
      sensitization.
FAU - Leishman, Emma
AU  - Leishman E
AD  - Department of Psychological and Brain Sciences, Indiana University, 1101 East 10 
      Street, Bloomington, IN, 47405, USA.
FAU - Kunkler, Phillip E
AU  - Kunkler PE
AD  - Stark Neurosciences Institute, Indiana University School of Medicine, 320 West 15 
      Street, Indianapolis, IN, 46202, USA.
FAU - Manchanda, Meera
AU  - Manchanda M
AD  - Department of Psychological and Brain Sciences, Indiana University, 1101 East 10 
      Street, Bloomington, IN, 47405, USA.
FAU - Sangani, Kishan
AU  - Sangani K
AD  - Department of Psychological and Brain Sciences, Indiana University, 1101 East 10 
      Street, Bloomington, IN, 47405, USA.
FAU - Stuart, Jordyn M
AU  - Stuart JM
AD  - Department of Psychological and Brain Sciences, Indiana University, 1101 East 10 
      Street, Bloomington, IN, 47405, USA.
FAU - Oxford, Gerry S
AU  - Oxford GS
AD  - Stark Neurosciences Institute, Indiana University School of Medicine, 320 West 15 
      Street, Indianapolis, IN, 46202, USA.
FAU - Hurley, Joyce H
AU  - Hurley JH
AD  - Stark Neurosciences Institute, Indiana University School of Medicine, 320 West 15 
      Street, Indianapolis, IN, 46202, USA.
FAU - Bradshaw, Heather B
AU  - Bradshaw HB
AD  - Department of Psychological and Brain Sciences, Indiana University, 1101 East 10 
      Street, Bloomington, IN, 47405, USA.
LA  - eng
GR  - R01 DA006668/DA/NIDA NIH HHS/United States
GR  - T32 DA024628/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20170517
PL  - United States
TA  - Neurobiol Pain
JT  - Neurobiology of pain (Cambridge, Mass.)
JID - 101705141
PMC - PMC5802349
MID - NIHMS871884
OTO - NOTNLM
OT  - Lipidomics
OT  - TRPA1
OT  - TRPV1
OT  - acrolein
OT  - endogenous cannabinoid
OT  - lipoamine
OT  - migraine
EDAT- 2018/02/13 06:00
MHDA- 2018/02/13 06:01
PMCR- 2017/04/01
CRDT- 2018/02/13 06:00
PHST- 2018/02/13 06:00 [entrez]
PHST- 2018/02/13 06:00 [pubmed]
PHST- 2018/02/13 06:01 [medline]
PHST- 2017/04/01 00:00 [pmc-release]
AID - S2452-073X(17)30002-8 [pii]
AID - 10.1016/j.ynpai.2017.03.001 [doi]
PST - ppublish
SO  - Neurobiol Pain. 2017 Jan-Jul;1:28-36. doi: 10.1016/j.ynpai.2017.03.001. Epub 2017 
      May 17.