Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction.
Quantitative trait locus mapping of chemical/inflammatory pain in the mouse identified the Avpr1a gene, which encodes the vasopressin-1A receptor (V1AR), as being responsible for strain-dependent pain sensitivity to formalin and capsaicin. A genetic association study in humans revealed the influence of a single nucleotide polymorphism (rs10877969) in AVPR1A on capsaicin pain levels, but only in male subjects reporting stress at the time of testing. The analgesic efficacy of the vasopressin analog desmopressin revealed a similar interaction between the drug and acute stress, as desmopressin inhibition of capsaicin pain was only observed in nonstressed subjects. Additional experiments in mice confirmed the male-specific interaction of V1AR and stress, leading to the conclusion that vasopressin activates endogenous analgesia mechanisms unless they have already been activated by stress. These findings represent, to the best of our knowledge, the first explicit demonstration of analgesic efficacy depending on the emotional state of the recipient, and illustrate the heuristic power of a bench-to-bedside-to-bench translational strategy.
Department of Psychology and Centre for Research on Pain, McGill University, Montreal, Quebec, Canada. jeffrey.mogil@mcgill.ca
Jeffrey S
JS
Mogil
Robert E
RE
Sorge
Michael L
ML
LaCroix-Fralish
Shad B
SB
Smith
Anny
A
Fortin
Susana G
SG
Sotocinal
Jennifer
J
Ritchie
Jean-Sebastien
JS
Austin
Ara
A
Schorscher-Petcu
Kara
K
Melmed
Jan
J
Czerminski
Rosalie A
RA
Bittong
J Brad
JB
Mokris
John K
JK
Neubert
Claudia M
CM
Campbell
Robert R
RR
Edwards
James N
JN
Campbell
Jacqueline N
JN
Crawley
William R
WR
Lariviere
Margaret R
MR
Wallace
Wendy F
WF
Sternberg
Carey D
CD
Balaban
Inna
I
Belfer
Roger B
RB
Fillingim
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000009:adverse effects; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D056726:Genetic Association Studies; D006185:Habituation, Psychophysiologic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008970:Molecular Weight; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci; D017483:Receptors, Vasopressin / Q000172:deficiency / Q000235:genetics; D012737:Sex Factors; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology; D014667:Vasopressins / Q000627:therapeutic use*
D000700:Analgesics; D017483:Receptors, Vasopressin; D014667:Vasopressins; D003894:Deamino Arginine Vasopressin; D002211:Capsaicin