Attenuated cold sensitivity in TRPM8 null mice.
Thermosensation is an essential sensory function that is subserved by a variety of transducer molecules, including those from the Transient Receptor Potential (TRP) ion channel superfamily. One of its members, TRPM8 (CMR1), a ligand-gated, nonselective cation channel, is activated by both cold and chemical stimuli in vitro. However, its roles in cold thermosensation and pain in vivo have not been fully elucidated. Here, we show that sensory neurons derived from TRPM8 null mice lack detectable levels of TRPM8 mRNA and protein and that the number of these neurons responding to cold (18 degrees C) and menthol (100 microM) is greatly decreased. Furthermore, compared with WT mice, TRPM8 null mice display deficiencies in certain behaviors, including icilin-induced jumping and cold sensation, as well as a significant reduction in injury-induced responsiveness to acetone cooling. These results suggest that TRPM8 may play an important role in certain types of cold-induced pain in humans.
Colburn
Raymond W
RW
Analgesics Team, East Coast Research and Early Development, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Spring House, PA 19477-0776, USA.
Lubin
Mary Lou
ML
Stone
Dennis J
DJ
Wang
Yan
Y
Lawrence
Danielle
D
D'Andrea
Michael R
MR
Brandt
Michael R
MR
Liu
Yi
Y
Flores
Christopher M
CM
Qin
Ning
N
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D003080:Cold Temperature; D005727:Ganglia, Spinal / Q000166:cytology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D000432:Methanol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000379:methods; D011744:Pyrimidinones / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D050053:TRPM Cation Channels / Q000172:deficiency*; D013697:Thermosensing / Q000235:genetics*
D011744:Pyrimidinones; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; C490483:icilin; D002211:Capsaicin; D002118:Calcium; D000432:Methanol