Transient receptor potential A1 mediates gastric distention-induced visceral pain in rats.
BACKGROUND
Transient receptor potential (TRP)A1, a member of the TRP family of ion channels, has been proposed to function in diverse sensory processes, including thermosensation and pain. However, TRPA1 has not been directly implicated in stomach mechanosensation, and its contribution to acute visceral pain from this organ is unknown. Here, we investigated the expression of TRPA1 in primary sensory afferents and its involvement in visceral hypersensitivity in rats.


METHODS
We examined TRPA1 expression in the dorsal root ganglion (DRG), nodose ganglion (NG), and stomach of rats by using immunohistochemistry. Electromyographic responses to gastric distention (GD) were recorded from the acromiotrapezius muscle in TRPA1 knockdown rats and in control rats.


RESULTS
TRPA1 was predominantly expressed with sensory neuropeptides in DRG and NG neurons, and in nerve fibres in the rat stomach. Gastric distention induced the activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) in DRG and NG neurons 2 min after stimulation, and most of the phosphorylated-ERK1/2-labelled DRG neurons were TRPA1-positive neurons. Intrathecal injection of TRPA1 antisense attenuated the visceromotor response, and suppressed ERK1/2 activation in the DRG, but not NG, neurons produced by GD. Furthermore, intrathecal and intraperitoneal injections of the TRPA1 inhibitor HC-03003 suppressed the response to noxious GD.


CONCLUSIONS
The activation of TRPA1 in DRG neurons by noxious GD may be involved in acute visceral pain. Our findings point to the potential blockade of TRPA1 in primary afferents as a new therapeutic target for the reduction of visceral hypersensitivity.
Kondo
T
T
Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Obata
K
K
Miyoshi
K
K
Sakurai
J
J
Tanaka
J
J
Miwa
H
H
Noguchi
K
K
D015746:Abdominal Pain / Q000378:metabolism* / Q000503:physiopathology; D000344:Afferent Pathways / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D013271:Gastric Dilatation / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013153:Splanchnic Nerves / Q000503:physiopathology; D013194:Staining and Labeling; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017833:Visceral Afferents / Q000378:metabolism*
D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D048052:Mitogen-Activated Protein Kinase 3