Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.
The vanilloid receptor-1 (VR1) is a ligand-gated, non-selective cation channel expressed predominantly by sensory neurons. VR1 responds to noxious stimuli including capsaicin, the pungent component of chilli peppers, heat and extracellular acidification, and it is able to integrate simultaneous exposure to these stimuli. These findings and research linking capsaicin with nociceptive behaviours (that is, responses to painful stimuli in animals have led to VR1 being considered as important for pain sensation. Here we have disrupted the mouse VR1 gene using standard gene targeting techniques. Small diameter dorsal root ganglion neurons isolated from VR1-null mice lacked many of the capsaicin-, acid- and heat-gated responses that have been previously well characterized in small diameter dorsal root ganglion neurons from various species. Furthermore, although the VR1-null mice appeared normal in a wide range of behavioural tests, including responses to acute noxious thermal stimuli, their ability to develop carrageenan-induced thermal hyperalgesia was completely absent. We conclude that VR1 is required for inflammatory sensitization to noxious thermal stimuli but also that alternative mechanisms are sufficient for normal sensation of noxious heat.
Davis
J B
JB
Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, UK. John_B_Davis@sbphrd.com
Gray
J
J
Gunthorpe
M J
MJ
Hatcher
J P
JP
Davey
P T
PT
Overend
P
P
Harries
M H
MH
Latcham
J
J
Clapham
C
C
Atkinson
K
K
Hughes
S A
SA
Rance
K
K
Grau
E
E
Harper
A J
AJ
Pugh
P L
PL
Rogers
D C
DC
Bingham
S
S
Randall
A
A
Sheardown
S A
SA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001522:Behavior, Animal; D002211:Capsaicin / Q000494:pharmacology; D002351:Carrageenan; D002478:Cells, Cultured; D004594:Electrophysiology; D063388:Endocannabinoids; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D018390:Gene Targeting; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D006930:Hyperalgesia / Q000209:etiology*; D007249:Inflammation / Q000139:chemically induced / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000502:physiology*; D010146:Pain; D053284:Polyunsaturated Alkamides; D011955:Receptors, Drug / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells; D050916:TRPV Cation Channels; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D002351:Carrageenan; D002211:Capsaicin; C078814:anandamide