Pharmacologic disruption of TRPV1-expressing primary sensory neurons but not genetic deletion of TRPV1 protects mice against pancreatitis.
OBJECTIVE
Transient receptor potential subtype vanilloid 1 (TRPV1) is an ion channel that is primarily expressed by primary sensory neurons where it mediates pain and heat sensation and participates in neurogenic inflammation. In this study, we examined the role of TRPV1 during neurogenic activation of pancreatic inflammation using a secretagogue-induced model in mice.


METHODS
A supramaximal dose of caerulein (50 microg/kg) was injected hourly for 12 hours. Mice lacking TRPV1 were compared to wild-type animals.


RESULTS
All the parameters: serum amylase, pancreatic myeloperoxidase activity, histological scoring, pancreatic wet weight/body weight ratio, and quantification of neurokinin-1 receptor internalization indicated that null mice were not protected from acute pancreatitis. However, when primary sensory neurons were ablated by injection of the neurotoxin and TRPV1 agonist, resiniferatoxin, pancreatitis was ameliorated in wild-type mice but not in null mice, indicating that nerves bearing TRPV1 are part of the inflammatory pathway in acute pancreatitis because disappearance significantly reduced the inflammatory response.


CONCLUSIONS
Nerves expressing TRPV1 participate in the neurogenic inflammation during acute pancreatitis. The lack of protection in TRPV1 null mice suggests that an alternate pathway to TRPV1 coexists in the same neurons.
Romac
Joelle M J
JM
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
McCall
Shannon J
SJ
Humphrey
John E
JE
Heo
Jinseok
J
Liddle
Rodger A
RA
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide / Q000494:pharmacology*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004705:Endocytosis; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010195:Pancreatitis / Q000235:genetics* / Q000517:prevention & control; D050916:TRPV Cation Channels / Q000187:drug effects / Q000235:genetics*
D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D002108:Ceruletide