PMID- 24005250
OWN - NLM
STAT- MEDLINE
DCOM- 20131227
LR  - 20211021
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 305
IP  - 9
DP  - 2013 Nov 1
TI  - Shivering and tachycardic responses to external cooling in mice are substantially 
      suppressed by TRPV1 activation but not by TRPM8 inhibition.
PG  - R1040-50
LID - 10.1152/ajpregu.00296.2013 [doi]
AB  - Mild decrease of core temperature (32-34 degrees C), also known as therapeutic 
      hypothermia, is a highly effective strategy of neuroprotection from ischemia and 
      holds significant promise in the treatment of stroke. However, induction of 
      hypothermia in conscious stroke patients is complicated by cold-defensive 
      responses, such as shivering and tachycardia. Although multiple thermoregulatory 
      responses may be altered by modulators of thermosensitive ion channels, TRPM8 
      (transient receptor potential melastatin 8) and TRPV1 (TRP vanilloid 1), it is 
      unknown whether these agents affect cold-induced shivering and tachycardia. The 
      current study aimed to determine the effects of TRPM8 inhibition and TRPV1 
      activation on the shivering and tachycardic responses to external cooling. 
      Conscious mice were treated with TRPM8 inhibitor compound 5 or TRPV1 agonist 
      dihydrocapsaicin (DHC) and exposed to cooling at 10 degrees C. Shivering was measured by 
      electromyography using implanted electrodes in back muscles, tachycardic response 
      by electrocardiography, and core temperature by wireless transmitters in the 
      abdominal cavity. The role of TRPM8 was further determined using TRPM8 KO mice. 
      TRPM8 ablation had no effect on total electromyographic muscle activity (vehicle: 
      24.0 +/- 1.8; compound 5: 23.8 +/- 2.0; TRPM8 KO: 19.7 +/- 1.9 V.s/min), tachycardia 
      (DeltaHR = 124 +/- 31; 121 +/- 13; 121 +/- 31 beats/min) and drop in core temperature (-3.6 
      +/- 0.1; -3.4 +/- 0.4; -3.6 +/- 0.5 degrees C) during cold exposure. TRPV1 activation 
      substantially suppressed muscle activity (vehicle: 25.6 +/- 3.0 vs. DHC: 5.1 +/- 2.0 
      V.s/min), tachycardia (DeltaHR = 204 +/- 25 vs. 3 +/- 35 beats/min) and produced a 
      profound drop in core temperature (-2.2 +/- 0.6 vs. -8.9 +/- 0.6 degrees C). In conclusion, 
      external cooling-induced shivering and tachycardia are suppressed by TRPV1 
      activation, but not by TRPM8 inhibition. This suggests that TRPV1 agonists may be 
      combined with external physical cooling to achieve more rapid and effective 
      hypothermia.
FAU - Feketa, Viktor V
AU  - Feketa VV
AD  - Department of Molecular Physiology and Biophysics Graduate Program, 
      Cardiovascular Sciences Track, Baylor College of Medicine, Houston, Texas;
FAU - Balasubramanian, Adithya
AU  - Balasubramanian A
FAU - Flores, Christopher M
AU  - Flores CM
FAU - Player, Mark R
AU  - Player MR
FAU - Marrelli, Sean P
AU  - Marrelli SP
LA  - eng
GR  - R01 HL-088435/HL/NHLBI NIH HHS/United States
GR  - R21 NS-077413/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130904
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Benzimidazoles)
RN  - 0 (TRPM Cation Channels)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, mouse)
RN  - 0 (Trpm8 protein, rat)
RN  - S07O44R1ZM (Capsaicin)
RN  - W9BV32M08A (dihydrocapsaicin)
SB  - IM
MH  - Animals
MH  - Benzimidazoles/*pharmacology
MH  - Capsaicin/*analogs & derivatives/pharmacology
MH  - Heart Rate/*drug effects
MH  - Hypothermia, Induced/*adverse effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Shivering/*drug effects
MH  - TRPM Cation Channels/*antagonists & inhibitors/deficiency/genetics/metabolism
MH  - TRPV Cation Channels/*agonists/metabolism
MH  - Tachycardia/etiology/genetics/metabolism/physiopathology/*prevention & control
MH  - Time Factors
PMC - PMC3840321
OTO - NOTNLM
OT  - dihydrocapsaicin
OT  - electromyography
OT  - pharmacological hypothermia
OT  - physical cooling
OT  - shivering
OT  - therapeutic hypothermia
OT  - transient receptor potential
EDAT- 2013/09/06 06:00
MHDA- 2013/12/29 06:00
PMCR- 2014/11/01
CRDT- 2013/09/06 06:00
PHST- 2013/09/06 06:00 [entrez]
PHST- 2013/09/06 06:00 [pubmed]
PHST- 2013/12/29 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - ajpregu.00296.2013 [pii]
AID - R-00296-2013 [pii]
AID - 10.1152/ajpregu.00296.2013 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2013 Nov 1;305(9):R1040-50. doi: 
      10.1152/ajpregu.00296.2013. Epub 2013 Sep 4.