title: Neonatal colon insult alters growth factor expression and TRPA1 responses in adult mice.
abstract: Inflammation or pain during neonatal development can result in long-term structural and functional alterations of nociceptive pathways, ultimately altering pain perception in adulthood. We have developed a mouse model of neonatal colon irritation (NCI) to investigate the plasticity of pain processing within the viscerosensory system. Mouse pups received an intracolonic administration of 2% mustard oil (MO) on postnatal days 8 and 10. Distal colons were processed at subsequent timepoints for myeloperoxidase (MPO) activity and growth factor expression. Adult mice were assessed for visceral hypersensitivity by measuring the visceromotor response during colorectal distension. Dorsal root ganglion (DRG) neurons from adult mice were retrogradely labeled from the distal colon and calcium imaging was used to measure transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) responses to acute application of capsaicin and MO, respectively. Despite the absence of inflammation (as indicated by MPO activity), neonatal exposure to intracolonic MO transiently maintained a higher expression level of growth factor messenger RNA (mRNA). Adult NCI mice displayed significant visceral hypersensitivity, as well as increased sensitivity to mechanical stimulation of the hindpaw, compared to control mice. The percentage of TRPA1-expressing colon afferents was significantly increased in NCI mice, however they displayed no increase in the percentage of TRPV1-immunopositive or capsaicin-sensitive colon DRG neurons. These results suggest that early neonatal colon injury results in a long-lasting visceral hypersensitivity, possibly driven by an early increase in growth factor expression and maintained by permanent changes in TRPA1 function.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Christianson
authors.forename: Klaus
authors.initials: K
authors.lastname: Bielefeldt
authors.forename: Sacha A
authors.initials: SA
authors.lastname: Malin
authors.forename: Brian M
authors.initials: BM
authors.lastname: Davis
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000166:cytology / Q000187:drug effects; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009149:Mustard Plant / Q000009:adverse effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000378:metabolism; D010938:Plant Oils / Q000009:adverse effects; D012333:RNA, Messenger / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*; D017833:Visceral Afferents / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010938:Plant Oils; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C048617:myelopeptides; D002772:Cholera Toxin; D002211:Capsaicin; D002118:Calcium; C027793:mustard oil