title: Anatomical and functional characterization of a duodeno-pancreatic neural reflex that can induce acute pancreatitis.
abstract: Neural cross talk between visceral organs may play a role in mediating inflammation and pain remote from the site of the insult. We hypothesized such a cross talk exists between the duodenum and pancreas, and further it induces pancreatitis in response to intraduodenal toxins. A dichotomous spinal innervation serving both the duodenum and pancreas was examined, and splanchnic nerve responses to mechanical stimulation of these organs were detected. This pathway was then excited on the duodenal side by exposure to ethanol followed by luminal mustard oil to activate transient receptor potential subfamily A, member 1 (TRPA1). Ninety minutes later, pancreatic inflammation was examined. Ablation of duodenal afferents by resiniferatoxin (RTX) or blocking TRPA1 by Chembridge (CHEM)-5861528 was used to further investigate the duodeno-pancreatic neural reflex via TRPA1. ~40% of dorsal root ganglia (DRG) from the spinal cord originated from both duodenum and pancreas via dichotomous peripheral branches; ~50% splanchnic nerve single units responded to mechanical stimulation of both organs. Ethanol sensitized TRPA1 currents in cultured DRG neurons. Pancreatic edema and myeloperoxidase activity significantly increased after intraduodenal ethanol followed by mustard oil (but not capsaicin) but significantly decreased after ablation of duodenal afferents by using RTX or blocking TRPA1 by CHEM-5861528. We found the existence of a neural cross talk between the duodenum and pancreas that can promote acute pancreatitis in response to intraduodenal chemicals. It also proves a previously unexamined mechanism by which alcohol can induce pancreatitis, which is novel both in terms of the site (duodenum), process (neurogenic), and receptor (TRPA1).
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University, Stanford, CA, USA.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Li
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Mohan
authors.initials: M
authors.lastname: Shenoy
authors.forename: Reetesh
authors.initials: R
authors.lastname: Pai
authors.forename: Liansheng
authors.initials: L
authors.lastname: Liu
authors.forename: Pankaj Jay
authors.initials: PJ
authors.lastname: Pasricha
mesh_terms: D000208:Acute Disease; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D004386:Duodenum / Q000294:innervation* / Q000502:physiology*; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D000431:Ethanol / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D010179:Pancreas / Q000294:innervation* / Q000502:physiology*; D010195:Pancreatitis / Q000473:pathology*; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000187:drug effects; D013153:Splanchnic Nerves / Q000502:physiology; D013270:Stomach / Q000294:innervation / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D004224:Diterpenes; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat; D000431:Ethanol; C024353:resiniferatoxin; D002211:Capsaicin