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Query: UMLS:C0000737 (
abdominal pain
)
31,184
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Abdominal pain
is one of the major symptoms in bowel obstruction (BO); its cellular mechanisms remain incompletely understood. We tested the hypothesis that mechanical stress in obstruction upregulates expression of nociception mediator nerve growth factor (NGF) in gut smooth muscle cells (SMCs), and NGF sensitizes primary sensory nerve to contribute to pain in BO. Partial colon obstruction was induced with a silicon band implanted in the distal bowel of Sprague-Dawley rats. Colon-projecting sensory neurons in the dorsal root ganglia (T13 to L2) were identified for patch-clamp and gene expression studies. Referred visceral sensitivity was assessed by measuring withdrawal response to stimulation by von Frey filaments in the lower abdomen. Membrane excitability of colon-projecting dorsal root ganglia neurons was significantly enhanced, and the withdrawal response to von Frey filament stimulation markedly increased in BO rats. The expression of NGF mRNA and protein was increased in a time-dependent manner (day 1-day 7) in colonic SMC but not in mucosa/submucosa of the obstructed colon. Mechanical stretch in vitro caused robust NGF mRNA and protein expression in colonic SMC. Treatment with anti-NGF antibody attenuated colon neuron hyperexcitability and referred hypersensitivity in BO rats. Obstruction led to significant increases of tetrodotoxin-resistant Na currents and mRNA expression of
Nav1.8
but not Nav1.6 and Nav1.7 in colon neurons; these changes were abolished by anti-NGF treatment. In conclusion, mechanical stress-induced upregulation of NGF in colon SMC underlies the visceral hypersensitivity in BO through increased gene expression and activity of tetrodotoxin-resistant Na channels in sensory neurons.
...
PMID:Pathogenesis of abdominal pain in bowel obstruction: role of mechanical stress-induced upregulation of nerve growth factor in gut smooth muscle cells. 2807 57
Background:
Hypoalgesic inflammatory bowel disease (IBD), a condition in which patients with active disease do not perceive and/or report
abdominal pain
, is associated with serious complications and there is a lack of cost-effective, reliable diagnostic methods to identify "at-risk" patients. The voltage-gated sodium channels (VGSC's), Na
v
1.7, Na
v
1.8, and Na
v
1.9, are preferentially expressed on nociceptive neurons, and have been implicated in visceral inflammatory pain. At least 29 VGSC single nucleotide polymorphisms (SNPs) have been implicated in chronic somatic pain syndromes, but little is known about their role in human visceral sensation. We hypothesized that disruptive VGSC polymorphisms result in anti-nociceptive behavior in IBD.
Methods and Findings:
We performed targeted exome sequencing and/or TaqMan genotyping to evaluate the Na
v
1.7, Na
v
1.8, and Na
v
1.9 genes (SCN9A,
SCN10A
and SCN11A) in 121 IBD patients (including 41 "hypoalgesic" IBD patients) and 86 healthy controls. Allelic and genotypic frequencies of polymorphisms were compared among study groups who had undergone characterization of intestinal inflammatory status and
abdominal pain
experience. Forty-nine total exonic SNPs were identified. The allelic frequency of only one non-synonymous SNP (rs6795970 [
SCN10A
]) approached significance in hypoalgesic IBD patients when compared to other IBD patients (
p
= 0.096, Fisher's exact test). Hypoalgesic IBD patients were more likely to be homozygous for this polymorphism (46 vs. 22%,
p
= 0.01, Fisher's exact test).
Conclusions:
This is the first human study to demonstrate a link between a genetic variant of
SCN10A
and
abdominal pain
perception in IBD. These findings provide key insights into visceral nociceptive physiology and new diagnostic and therapeutic targets to consider in IBD and other gastrointestinal conditions associated with chronic
abdominal pain
. Further studies are required to elucidate the precise pathophysiological impact of the rs6795970 polymorphism on human gastrointestinal nociception.
...
PMID:Homozygosity for the SCN10A Polymorphism rs6795970 Is Associated With Hypoalgesic Inflammatory Bowel Disease Phenotype. 3053 88
Na
V
1.8 channels play a crucial role in regulating the action potential in nociceptive neurons. A single nucleotide polymorphism in the human Na
V
1.8 gene
SCN10A
, A1073V (rs6795970, G>A), has been linked to the diminution of mechanical pain sensation as well as cardiac conduction abnormalities. Furthermore, studies have suggested that this polymorphism may result in a "loss-of-function" phenotype. In the present study, we performed genomic analysis of A1073V polymorphism presence in a cohort of patients undergoing sigmoid colectomy who provided information regarding perioperative pain and analgesic use. Homozygous carriers reported significantly reduced severity in postoperative
abdominal pain
compared with heterozygous and wild-type carriers. Homozygotes also trended toward using less analgesic/opiates during the postoperative period. We also heterologously expressed the wild-type and A1073V variant in rat superior cervical ganglion neurons. Electrophysiological testing demonstrated that the mutant Na
V
1.8 channels activated at more depolarized potentials compared with wild-type channels. Our study revealed that postoperative
abdominal pain
is diminished in homozygous carriers of A1073V and that this is likely due to reduced transmission of action potentials in nociceptive neurons. Our findings reinforce the importance of Na
V
1.8 and the A1073V polymorphism to pain perception. This information could be used to develop new predictive tools to optimize patient pain experience and analgesic use in the perioperative setting.
NEW & NOTEWORTHY
We present evidence that in a cohort of patients undergoing sigmoid colectomy, those homozygous for the Na
V
1.8 polymorphism (rs6795970) reported significantly lower
abdominal pain
scores than individuals with the homozygous wild-type or heterozygous genotype. In vitro electrophysiological recordings also suggest that the mutant Na
V
1.8 channel activates at more depolarizing potentials than the wild-type Na
+
channel, characteristic of hypoactivity. This is the first report linking the rs6795970 mutation with postoperative
abdominal pain
in humans.
...
PMID:Impact of the Na
V
1.8 variant, A1073V, on post-sigmoidectomy pain and electrophysiological function in rat sympathetic neurons. 3164 3
