PMID- 33990108
OWN - NLM
STAT- MEDLINE
DCOM- 20220323
LR  - 20230818
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Print)
IS  - 0304-3959 (Linking)
VI  - 163
IP  - 2
DP  - 2022 Feb 1
TI  - Inhibition of transient receptor potential vanilloid 1 and transient receptor 
      potential ankyrin 1 by mosquito and mouse saliva.
PG  - 299-307
LID - 10.1097/j.pain.0000000000002337 [doi]
AB  - Arthropods are the largest group of living organisms, and among them, mosquitoes 
      spread parasites and viruses causing deadly diseases. They can easily spread 
      these pathogens because of their painless skin piercing. Although the lack of 
      pain is mainly due to the thinness of their fascicle, it is possible that 
      mosquito saliva, which is discharged during their piercing, might also contribute 
      to it. If mosquito saliva contains antinociceptive substances, it should act on 
      the sensory neurons innervating the epidermis where there are several ion 
      channels that can detect noxious stimuli, such as the transient receptor 
      potential (TRP) channels. We found that mosquito head homogenates and mouse 
      saliva inhibit TRP vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) channels, either 
      heterologously expressed in HEK293T cells or endogenously expressed in native 
      mouse sensory neurons. Among the different substances contained in mosquito head 
      homogenates or mouse saliva, we have also identified sialorphin as a candidate 
      antinociceptive peptide because it showed similar inhibition effects on TRPV1 and 
      TRPA1. Finally, we confirmed the antinociceptive effects of mosquito head 
      homogenates, mouse saliva, and sialorphin in vivo by observing decreased 
      pain-related behaviors in mice coinjected with these substances. Similar 
      inhibitory effects of mosquito head homogenates and mouse saliva on TRPV1 and 
      TRPA1 suggest that the antinociceptive effects of saliva are universal, which 
      could explain why many animals including humans often lick their wounds. These 
      findings would lead to the development of novel and safe antinociceptive agents.
CI  - Copyright (c) 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on 
      behalf of the International Association for the Study of Pain.
FAU - Derouiche, Sandra
AU  - Derouiche S
AUID- ORCID: 0000-0002-5808-8303
AD  - Division of Cell Signaling, National Institute for Physiological Sciences, 
      National Institutes of Natural Sciences (NIPS), Okazaki, Japan.
AD  - Thermal Biology Group, Exploratory Research Center on Life and Living Systems 
      (ExCELLS), National Institutes of Natural Sciences, Okazaki, Japan.
AD  - Department of Physiological Sciences, School of Life Science, SOKENDAI (The 
      Graduate University for Advanced Studies), Okazaki, Japan.
FAU - Li, Tianbang
AU  - Li T
AUID- ORCID: 0000-0001-6189-1861
AD  - Division of Cell Signaling, National Institute for Physiological Sciences, 
      National Institutes of Natural Sciences (NIPS), Okazaki, Japan.
AD  - Thermal Biology Group, Exploratory Research Center on Life and Living Systems 
      (ExCELLS), National Institutes of Natural Sciences, Okazaki, Japan.
FAU - Sakai, Yuya
AU  - Sakai Y
AUID- ORCID: 0000-0001-6249-3654
AD  - Faculty of Engineering Science, Kansai University, Osaka, Japan.
FAU - Uta, Daisuke
AU  - Uta D
AD  - Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, 
      University of Toyama, Toyama, Japan.
FAU - Aoyagi, Seiji
AU  - Aoyagi S
AUID- ORCID: 0000-0003-0177-7316
AD  - Faculty of Engineering Science, Kansai University, Osaka, Japan.
FAU - Tominaga, Makoto
AU  - Tominaga M
AUID- ORCID: 0000-0003-3111-3772
AD  - Division of Cell Signaling, National Institute for Physiological Sciences, 
      National Institutes of Natural Sciences (NIPS), Okazaki, Japan.
AD  - Thermal Biology Group, Exploratory Research Center on Life and Living Systems 
      (ExCELLS), National Institutes of Natural Sciences, Okazaki, Japan.
AD  - Department of Physiological Sciences, School of Life Science, SOKENDAI (The 
      Graduate University for Advanced Studies), Okazaki, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (Analgesics)
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (TRPA1 protein, human)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, human)
SB  - IM
MH  - *Analgesics/metabolism
MH  - Animals
MH  - *Culicidae/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Mice
MH  - *Pain/metabolism
MH  - *Saliva/metabolism
MH  - Sensory Receptor Cells/metabolism
MH  - *TRPA1 Cation Channel/antagonists & inhibitors/metabolism
MH  - *TRPV Cation Channels/antagonists & inhibitors/metabolism
PMC - PMC8756345
COIS- The authors have no conflicts of interest to declare. Sponsorships or competing 
      interests that may be relevant to content are disclosed at the end of this 
      article.
EDAT- 2021/05/15 06:00
MHDA- 2022/03/24 06:00
PMCR- 2022/01/13
CRDT- 2021/05/14 20:27
PHST- 2020/11/02 00:00 [received]
PHST- 2021/04/28 00:00 [accepted]
PHST- 2021/05/15 06:00 [pubmed]
PHST- 2022/03/24 06:00 [medline]
PHST- 2021/05/14 20:27 [entrez]
PHST- 2022/01/13 00:00 [pmc-release]
AID - 00006396-202202000-00007 [pii]
AID - PAIN-D-20-01410 [pii]
AID - 10.1097/j.pain.0000000000002337 [doi]
PST - ppublish
SO  - Pain. 2022 Feb 1;163(2):299-307. doi: 10.1097/j.pain.0000000000002337.