PMID- 21737202
OWN - NLM
STAT- MEDLINE
DCOM- 20120625
LR  - 20220316
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Print)
IS  - 0304-3959 (Linking)
VI  - 152
IP  - 10
DP  - 2011 Oct
TI  - Serotonin increases the functional activity of capsaicin-sensitive rat trigeminal 
      nociceptors via peripheral serotonin receptors.
PG  - 2267-2276
LID - 10.1016/j.pain.2011.06.002 [doi]
AB  - Peripheral serotonin (5HT) has been implicated in migraine and temporomandibular 
      pain disorders in humans and animal models and yet the mechanism(s) by which 5HT 
      evokes pain remains unclear. Trigeminal pain can be triggered by activation of 
      the transient receptor potential V1 channel (TRPV1), expressed by a subset of 
      nociceptive trigeminal ganglia (TG) neurons and gated by capsaicin, noxious heat, 
      and other noxious stimuli. As 5HT is released in the periphery during 
      inflammation and evokes thermal hyperalgesia, and TRPV1 is essential for thermal 
      hyperalgesia, we hypothesized that 5HT increases the activity of 
      capsaicin-sensitive trigeminal neurons and that this increase can be attenuated 
      by pharmacologically targeting peripheral 5HT receptors. TG cultures were 
      pretreated with 5HT (10 nM-100 muM), sumatriptan (5HT(1B/1D) agonist), ketanserin 
      (5HT(2A) antagonist), granisetron (5HT(3) antagonist), or vehicle prior to 
      capsaicin (30-50 nM). Single-cell accumulation of intracellular calcium was 
      recorded or calcitonin gene-related peptide (CGRP) release was measured following 
      each treatment. In addition, using in situ hybridization and 
      immunohistochemistry, we detected the colocalization of 5HT(1B), 5HT(1D), 
      5HT(2A), and 5HT(3A), but not 5HT(2C) mRNA with TRPV1 in TG cells. 5HT 
      pretreatment evoked a significant increase in calcium accumulation in 
      capsaicin-sensitive trigeminal neurons and enhanced capsaicin-evoked CGRP 
      release, but had no significant effect when given alone. Sumatriptan, ketanserin, 
      and granisetron treatment attenuated calcium accumulation and 5HT enhancement of 
      capsaicin-evoked CGRP release. Together these results indicate that 5HT increases 
      the activity of capsaicin-sensitive peripheral nociceptors, which can be 
      attenuated by pharmacologically targeting peripheral 5HT receptors, thereby 
      providing a mechanistic basis for peripheral craniofacial pain therapy.
CI  - Copyright (c) 2011 International Association for the Study of Pain. Published by 
      Elsevier B.V. All rights reserved.
FAU - Loyd, Dayna R
AU  - Loyd DR
AD  - Department of Endodontics, University of Texas Health Science Center at San 
      Antonio, San Antonio, TX, USA Department of Pharmacology, University of Texas 
      Health Science Center at San Antonio, San Antonio, TX, USA.
FAU - Weiss, Gabriela
AU  - Weiss G
FAU - Henry, Michael A
AU  - Henry MA
FAU - Hargreaves, Kenneth M
AU  - Hargreaves KM
LA  - eng
GR  - T32 DE014318/DE/NIDCR NIH HHS/United States
GR  - T32 DE14318/DE/NIDCR NIH HHS/United States
GR  - R01 NS072890-01/NS/NINDS NIH HHS/United States
GR  - U54RR02438/RR/NCRR NIH HHS/United States
GR  - F32 DE021309/DE/NIDCR NIH HHS/United States
GR  - R01 NS72890/NS/NINDS NIH HHS/United States
GR  - HHSN-271-2008-00025-C/PHS HHS/United States
GR  - R01 DE015576-06/DE/NIDCR NIH HHS/United States
GR  - R01 DE015576/DE/NIDCR NIH HHS/United States
GR  - F32 DE021309-01/DE/NIDCR NIH HHS/United States
GR  - R01 NS072890/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110706
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 333DO1RDJY (Serotonin)
RN  - S07O44R1ZM (Capsaicin)
SB  - IM
MH  - Animals
MH  - Capsaicin/*toxicity
MH  - Disease Models, Animal
MH  - Male
MH  - Nociceptors/drug effects/pathology/*physiology
MH  - Primary Cell Culture
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin/*physiology
MH  - Serotonin/*physiology
MH  - Serotonin Antagonists/metabolism/pharmacology
MH  - Serotonin Receptor Agonists/metabolism/pharmacology
MH  - Trigeminal Neuralgia/drug therapy/metabolism/pathology
MH  - Up-Regulation/*physiology
PMC - PMC3183408
MID - NIHMS306669
COIS- The authors report no conflicts of interest.
EDAT- 2011/07/09 06:00
MHDA- 2012/06/26 06:00
PMCR- 2012/10/01
CRDT- 2011/07/09 06:00
PHST- 2010/12/10 00:00 [received]
PHST- 2011/06/01 00:00 [revised]
PHST- 2011/06/06 00:00 [accepted]
PHST- 2011/07/09 06:00 [entrez]
PHST- 2011/07/09 06:00 [pubmed]
PHST- 2012/06/26 06:00 [medline]
PHST- 2012/10/01 00:00 [pmc-release]
AID - 00006396-201110000-00016 [pii]
AID - 10.1016/j.pain.2011.06.002 [doi]
PST - ppublish
SO  - Pain. 2011 Oct;152(10):2267-2276. doi: 10.1016/j.pain.2011.06.002. Epub 2011 Jul 
      6.