Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation.

The transient receptor potential (TRP) channels TRPV1 and TRPA1 have each been associated with regulation of efferent properties of primary afferent neurons that initiate neurogenic inflammation and are required for the development of inflammatory hyperalgesia. To evaluate the role of these channels in producing pain during pancreatic inflammation, we studied pancreatic nodose ganglion (NG) and dorsal root ganglion (DRG) sensory neurons (identified by content of retrograde tracer) and behavioral outcomes in a mouse model of acute pancreatitis. Pancreatic inflammation was induced by 8 hourly injections of cerulein (50 μg/kg). The extent of inflammation, pancreatic neuron TRP channel expression and function and excitability, and pain-related behaviors were evaluated over the course of the following week. Histology and myeloperoxidase activity confirmed pancreatic inflammation that was associated with increased excitability and messenger RNA expression of the TRP channels in NG and DRG pancreatic neurons. Calcium imaging of pancreatic NG and DRG neurons from mice given cerulein revealed increased responses to TRP agonists. TRPV1 and TRPA1 antagonists attenuated cerulein-induced pain behaviors and pancreatic inflammation; they had a synergistic effect. Pancreatic inflammation significantly increased the expression and functional properties of TRPV1 and TRPA1, as well as the excitability of pancreatic sensory neurons in vagal and spinal pathways. TRP channel antagonists acted synergistically to reverse pancreatic inflammation and associated pain behaviors; reagents that target interactions between these channels might be developed to reduce pain in patients with acute pancreatitis.

Schwartz ES ，Christianson JA ，Chen X ，La JH ，Davis BM ，Albers KM ，Gebhart GF ... -  《-》

TRPV1 and TRPA1 antagonists prevent the transition of acute to chronic inflammation and pain in chronic pancreatitis.

Schwartz ES ，La JH ，Scheff NN ，Davis BM ，Albers KM ，Gebhart GF ... -  《-》

Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice.

Ceppa E ，Cattaruzza F ，Lyo V ，Amadesi S ，Pelayo JC ，Poole DP ，Vaksman N ，Liedtke W ，Cohen DM ，Grady EF ，Bunnett NW ，Kirkwood KS ... -  《-》

Excitation and modulation of TRPA1, TRPV1, and TRPM8 channel-expressing sensory neurons by the pruritogen chloroquine.

Than JY ，Li L ，Hasan R ，Zhang X ... -  《-》

TRPV1 and TRPA1 Channels Are Both Involved Downstream of Histamine-Induced Itch.

Wilzopolski J ，Kietzmann M ，Mishra SK ，Stark H ，Bäumer W ，Rossbach K ... -  《Biomolecules》