TRPA1 Contributes to Cold Hypersensitivity

被引：222

作者：

del Camino, Donato ^{[1
]}

Murphy, Sarah ^{[1
]}

Heiry, Melissa ^{[1
]}

Barrett, Lee B. ^{[4
,5
]}

Earley, Taryn J. ^{[3
]}

Cook, Colby A. ^{[1
]}

Petrus, Matt J. ^{[2
]}

Zhao, Michael ^{[1
]}

D'Amours, Marc ^{[1
]}

Deering, Nate ^{[1
]}

Brenner, Gary J. ^{[6
,7
]}

Costigan, Michael ^{[4
,5
]}

Hayward, Neil J. ^{[1
]}

Chong, Jayhong A. ^{[1
]}

Fanger, Christopher M. ^{[1
]}

Woolf, Clifford J. ^{[4
,5
]}

Patapoutian, Ardem ^{[2
,3
]}

Moran, Magdalene M. ^{[1
]}

机构：

[1] Hydra Biosci Inc, Cambridge, MA 02139 USA

[2] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA

[3] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA

[4] Childrens Hosp Boston, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[6] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neuronal Plast Res Grp, Charlestown, MA 02129 USA

[7] Harvard Univ, Sch Med, Charlestown, MA 02129 USA

来源：

JOURNAL OF NEUROSCIENCE | 2010年 / 30卷 / 45期

基金：

美国国家卫生研究院;

关键词：

RECEPTOR POTENTIAL A1; ION-CHANNEL TRPA1; SENSORY NEURONS; COVALENT MODIFICATION; NOCICEPTIVE NEURONS; NERVE INJURY; CALCIUM-IONS; PAIN; ACTIVATION; TRPM8;

D O I：

10.1523/JNEUROSCI.2580-10.2010

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

TRPA1 is a nonselective cation channel expressed by nociceptors. Although it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions in which reactive oxygen species and proinflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but not Trpa1(-/-) mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide] reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain.

引用

页码：15165 / 15174

页数：10

共 39 条

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