TREK-1, a K+ channel involved in polymodal pain perception.
The TREK-1 channel is a temperature-sensitive, osmosensitive and mechano-gated K+ channel with a regulation by Gs and Gq coupled receptors. This paper demonstrates that TREK-1 qualifies as one of the molecular sensors involved in pain perception. TREK-1 is highly expressed in small sensory neurons, is present in both peptidergic and nonpeptidergic neurons and is extensively colocalized with TRPV1, the capsaicin-activated nonselective ion channel. Mice with a disrupted TREK-1 gene are more sensitive to painful heat sensations near the threshold between anoxious warmth and painful heat. This phenotype is associated with the primary sensory neuron, as polymodal C-fibers were found to be more sensitive to heat in single fiber experiments. Knockout animals are more sensitive to low threshold mechanical stimuli and display an increased thermal and mechanical hyperalgesia in conditions of inflammation. They display a largely decreased pain response induced by osmotic changes particularly in prostaglandin E2-sensitized animals. TREK-1 appears as an important ion channel for polymodal pain perception and as an attractive target for the development of new analgesics.
Alloui
Abdelkrim
A
Laboratoire de Pharmacologie Médicale EA 3848 INSERM/Faculté de Médecine/CHU, Clermont-Ferrand, France.
Zimmermann
Katharina
K
Mamet
Julien
J
Duprat
Fabrice
F
Noël
Jacques
J
Chemin
Jean
J
Guy
Nicolas
N
Blondeau
Nicolas
N
Voilley
Nicolas
N
Rubat-Coudert
Catherine
C
Borsotto
Marc
M
Romey
Georges
G
Heurteaux
Catherine
C
Reeh
Peter
P
Eschalier
Alain
A
Lazdunski
Michel
M