vasoactive-intestinal-peptide and Constriction--Pathologic

Vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) in dorsal root ganglia (DRGs) are known to be upregulated and to contribute to the mechanisms of neuropathic pain following peripheral nerve injury. Moreover, transcription factor c-Jun regulates the expressions of both VIP and NPY in cultured DRG neurons. To elucidate the role of c-Jun in the induction of neuropathic pain hypersensitivity, we examined whether activated c-Jun affects pain behavior and the expressions of VIP and NPY following chronic constriction injury (CCI) of rat sciatic nerve. Intrathecal treatment with c-jun antisense oligodeoxynucleotides (AS-ODN) significantly reduced mechanical allodynia, but not thermal hyperalgesia following CCI. In addition, c-jun AS-ODN also suppressed the remarkable elevations of VIP and NPY mRNAs and the percentages of phosphorylated c-Jun-, VIP-, and NPY-immunoreactive neurons observed in DRGs following CCI. These results show that the activation of c-Jun in DRGs induces VIP and NPY upregulation and contributes to the pathogenesis of neuropathic pain following CCI.

Topics: Animals; Constriction, Pathologic; Ganglia, Spinal; Hot Temperature; Hypesthesia; Immunohistochemistry; Male; Neuralgia; Neurons; Neuropeptide Y; Oligonucleotides, Antisense; Phosphorylation; Physical Stimulation; Proto-Oncogene Proteins c-jun; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sciatic Nerve; Time Factors; Up-Regulation; Vasoactive Intestinal Peptide

Colonic strictures are rare in patients who have cystic fibrosis, but recently have developed in those who have been treated with delayed-release high-dose pancreatic enzyme supplements. Colonic strictures from eight such pediatric patients showed neural abnormalities consisting of ganglion cell hyperplasia and ectopia, and intermyenteric plexus hyperplasia. Cholinergic and adrenergic stains of mucosal nerve fibers were more prominent in histological sections of the cystic fibrosis strictures than in sections from colons of children without cystic fibrosis. The mean grade of staining with acetylcholinesterase in the lamina propria of the strictured cystic fibrosis colons was 2.38 +/- 1.25, compared with .93 +/- .93 (P < .055) in bowels from children without cystic fibrosis. The mean grade for tyrosine hydroxylase staining in the lamina propria was 2 +/- .97 in the strictures and was .79 +/- .81 (P < .05) in the bowels of children who did not have cystic fibrosis. Vasoactive intestinal peptide staining in bowels from children with cystic fibrosis with and without stricture did not differ significantly from that of children without cystic fibrosis. Vasculopathy consisting of fibrointimal hyperplasia in submucosal veins and mesenteric arteries was found only in colonic strictures owing to cystic fibrosis. Colonic strictures in patients with cystic fibrosis who received high-dose pancreatic enzyme supplements contain ganglion cell abnormalities, and mucosal cholinergic and adrenergic activity may be increased in these strictures. The stricture vasculopathy may be drug-related and/or related to increased catecholamine activity.

Topics: Acetylcholinesterase; Adolescent; Adrenergic Fibers; Catecholamines; Child; Child, Preschool; Cholinergic Fibers; Choristoma; Colon; Colonic Diseases; Constriction, Pathologic; Cystic Fibrosis; Female; Ganglia; Humans; Hyperplasia; Infant, Newborn; Intestinal Mucosa; Male; Mesenteric Arteries; Pancreas; Pancreatic Extracts; Peripheral Nervous System Diseases; Tunica Intima; Tyrosine 3-Monooxygenase; Vascular Diseases; Vasoactive Intestinal Peptide

We studied in vivo the effects of pre-inhalations of vasoactive intestinal polypeptide (VIP) and a precursor analogue of VIP (Leu17 VIP-Gly-Lys: preVIP) in mongrel dogs bronchoconstricted by ascaris. An inhalation of preVIP solution (2 mg/5 ml saline) gave significant protection for 120 min against increases in respiratory resistance (Rrs) and decreases in dynamic compliance (Cdyn) induced by ascaris challenges. An inhalation of VIP solution (2 mg/ml saline) also gave significant protection for 120 min against increases in Rrs induced by ascaris challenges. Protective effect of the inhalation of preVIP against ascaris-induced bronchoconstriction was more potent than that of VIP. The inhalations of preVIP and VIP solution did not change systemic blood pressure or heart rate. These results indicate that inhalations of preVIP or VIP solution would attenuate ascaris-induced bronchoconstriction in dogs without affecting cardiovascular dynamics.

Topics: Administration, Inhalation; Airway Resistance; Animals; Antigens, Helminth; Ascaris; Bronchi; Constriction, Pathologic; Dogs; Peptide PHI; Protein Precursors; Vasoactive Intestinal Peptide