PMID- 20647494
OWN - NLM
STAT- MEDLINE
DCOM- 20101021
LR  - 20211020
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 335
IP  - 1
DP  - 2010 Oct
TI  - 17beta-estradiol rapidly enhances bradykinin signaling in primary sensory neurons 
      in vitro and in vivo.
PG  - 190-6
LID - 10.1124/jpet.110.167445 [doi]
AB  - Many studies have demonstrated that premenopausal women are at increased risk for 
      various pain disorders. Pain-sensing neurons, termed "nociceptors," in the 
      trigeminal ganglia (TG) and dorsal root ganglia (DRG) express receptors for 
      inflammatory mediators and noxious physical stimuli and transmit signals for 
      central processing of pain sensation. Estrogen receptors (ERs) are also expressed 
      on nociceptors in the TG and DRG, and there is ample literature to suggest that 
      activation of ERs can influence pain mechanisms. However, the mechanism for ER 
      modulation of nociceptor activity is incompletely understood. The aim of this 
      study was to characterize the effect of 17beta-estradiol (17beta-E(2)) on signaling of 
      the inflammatory mediator bradykinin (BK) in primary cultures of rat sensory 
      neurons and a behavioral model of thermal allodynia in rats. Here, we show that 
      exposure to 17beta-E(2) rapidly (within 15 min) enhanced responses to BK in vitro 
      and in vivo. The 17beta-E(2)-mediated enhancement of BK signaling was not blocked by 
      the transcription inhibitor anisomycin and was mediated by a membrane-associated 
      ER. The effect of 17beta-E(2) to enhance BK responses required activation of 
      beta1-containing, RGD-binding integrins. These data show that 17beta-E(2) rapidly 
      enhances inflammatory mediator responses both in vitro and in vivo and suggest 
      that 17beta-E(2) acting at primary sensory pain neurons may participate in 
      regulating the sensitivity of women to painful stimuli.
FAU - Rowan, Matthew P
AU  - Rowan MP
AD  - Department of Pharmacology, University of Texas Health Science Center, San 
      Antonio, TX 78229-3900, USA.
FAU - Berg, Kelly A
AU  - Berg KA
FAU - Milam, Stephen B
AU  - Milam SB
FAU - Jeske, Nathan A
AU  - Jeske NA
FAU - Roberts, James L
AU  - Roberts JL
FAU - Hargreaves, Kenneth M
AU  - Hargreaves KM
FAU - Clarke, William P
AU  - Clarke WP
LA  - eng
GR  - T32 DE014318/DE/NIDCR NIH HHS/United States
GR  - R01-NS055835/NS/NINDS NIH HHS/United States
GR  - R01 NS061884/NS/NINDS NIH HHS/United States
GR  - T32DE14318/DE/NIDCR NIH HHS/United States
GR  - R01 NS055835/NS/NINDS NIH HHS/United States
GR  - R01-NS058655/NS/NINDS NIH HHS/United States
GR  - R01 NS058655/NS/NINDS NIH HHS/United States
GR  - R01-NS061884/NS/NINDS NIH HHS/United States
GR  - R01 NS061884-02/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100720
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Inositol Phosphates)
RN  - 0 (Integrins)
RN  - 0 (Nucleic Acid Synthesis Inhibitors)
RN  - 4TI98Z838E (Estradiol)
RN  - 6C74YM2NGI (Anisomycin)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Animals
MH  - Anisomycin/pharmacology
MH  - Behavior, Animal/drug effects
MH  - Bradykinin/*physiology
MH  - Cells, Cultured
MH  - Estradiol/*pharmacology
MH  - Female
MH  - Ganglia, Spinal/cytology/drug effects
MH  - Inositol Phosphates/metabolism
MH  - Integrins/antagonists & inhibitors/metabolism
MH  - Male
MH  - Nerve Endings/drug effects
MH  - Nucleic Acid Synthesis Inhibitors/pharmacology
MH  - Pain/psychology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sensory Receptor Cells/drug effects/*physiology
MH  - Signal Transduction/*drug effects
MH  - Trigeminal Ganglion/cytology/drug effects
MH  - Type C Phospholipases/metabolism
PMC - PMC2957773
EDAT- 2010/07/22 06:00
MHDA- 2010/10/22 06:00
PMCR- 2011/10/01
CRDT- 2010/07/22 06:00
PHST- 2010/07/22 06:00 [entrez]
PHST- 2010/07/22 06:00 [pubmed]
PHST- 2010/10/22 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - jpet.110.167445 [pii]
AID - 3627658 [pii]
AID - 10.1124/jpet.110.167445 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2010 Oct;335(1):190-6. doi: 10.1124/jpet.110.167445. Epub 
      2010 Jul 20.