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Polymorphisms in gene encoding TRPV1-receptor involved in pain perception are unrelated to chronic pancreatitis.

ABSTRACT: BACKGROUND: The major clinical feature in chronic pancreatitis is pain, but the genetic basis of pancreatic pain in chronic pancreatitis is poorly understood. The transient receptor potential vanilloid receptor 1 (TRPV1) gene has been associated with pain perception, and genetic variations in TRPV1 may modify the presence and phenotype of chronic pancreatitis. The aim of our study was to investigate the genetic variation of TRPV1 in Dutch patients with chronic pancreatitis and healthy controls. METHODS: We genotyped 4 SNPs (rs222749, rs222747, rs224534 and rs8065080) in 228 chronic pancreatitis-patients and 207 healthy controls by PCR, followed by restriction-fragment-length-polymorphism analysis and DNA sequencing. We generated 27 diplotypes and compared prevalence between patients and controls. RESULTS: There was no significant difference in allele frequency of the 4 TRPV1 gene SNPs in patients with chronic pancreatitis and healthy controls. Distribution of diplotypes was not statistically significantly different between patients and controls. CONCLUSION: TRPV1 diplotypes are not associated with chronic pancreatitis.

SUBMITTER: van Esch AA

PROVIDER: S-EPMC2813232 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Polymorphisms in gene encoding TRPV1-receptor involved in pain perception are unrelated to chronic pancreatitis.

van Esch Aura A J AA Lamberts Mark P MP te Morsche René H M RH van Oijen Martijn G H MG Jansen Jan B M J JB Drenth Joost P H JP

BMC gastroenterology 20091224

<h4>Background</h4>The major clinical feature in chronic pancreatitis is pain, but the genetic basis of pancreatic pain in chronic pancreatitis is poorly understood. The transient receptor potential vanilloid receptor 1 (TRPV1) gene has been associated with pain perception, and genetic variations in TRPV1 may modify the presence and phenotype of chronic pancreatitis. The aim of our study was to investigate the genetic variation of TRPV1 in Dutch patients with chronic pancreatitis and healthy con ...[more]

PMID: 20034385

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Project description:The parabrachial (PB) complex mediates both ascending nociceptive signaling and descending pain modulatory information in the affective/emotional pain pathway. We have recently reported that chronic pain is associated with amplified activity of PB neurons in a rat model of neuropathic pain. Here we demonstrate that similar activity amplification occurs in mice, and that this is related to suppressed inhibition to lateral parabrachial (LPB) neurons from the CeA in animals of either sex. Animals with pain after chronic constriction injury of the infraorbital nerve (CCI-Pain) displayed higher spontaneous and evoked activity in PB neurons, and a dramatic increase in after-discharges, responses that far outlast the stimulus, compared with controls. LPB neurons in CCI-Pain animals showed a reduction in inhibitory, GABAergic inputs. We show that, in both rats and mice, LPB contains few GABAergic neurons, and that most of its GABAergic inputs arise from CeA. These CeA GABA neurons express dynorphin, somatostatin, and/or corticotropin releasing hormone. We find that the efficacy of this CeA-LPB pathway is suppressed in chronic pain. Further, optogenetically stimulating this pathway suppresses acute pain, and inhibiting it, in naive animals, evokes pain behaviors. These findings demonstrate that the CeA-LPB pathway is critically involved in pain regulation, and in the pathogenesis of chronic pain.SIGNIFICANCE STATEMENT We describe a novel pathway, consisting of inhibition by dynorphin, somatostatin, and corticotropin-releasing hormone-expressing neurons in the CeA that project to the parabrachial nucleus. We show that this pathway regulates the activity of pain-related neurons in parabrachial nucleus, and that, in chronic pain, this inhibitory pathway is suppressed, and that this suppression is causally related to pain perception. We propose that this amygdalo-parabrachial pathway is a key regulator of both chronic and acute pain, and a novel target for pain relief.

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Polymorphisms in gene encoding TRPV1-receptor involved in pain perception are unrelated to chronic pancreatitis.

Publications

Polymorphisms in gene encoding TRPV1-receptor involved in pain perception are unrelated to chronic pancreatitis.

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