ArticlePloS one2012
Upregulation of cystathionine β-synthetase expression contributes to visceral hyperalgesia induced by heterotypic intermittent stress in rats.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.Frontiers in pharmacology · 2025Review
- The roles of hydrogen sulfide in renal physiology and disease states.Renal failure · 2022Review
- Hydrogen Sulfide Biomedical Research in China-20 Years of Hindsight.Antioxidants (Basel, Switzerland) · 2022Review
- Upregulation of Nav1.7 by endogenous hydrogen sulfide contributes to maintenance of neuropathic pain.International journal of molecular medicine · 2020Article
- CBS-Induced HEvidence-based complementary and alternative medicine : eCAM · 2020Article
- Neonatal Maternal Deprivation Followed by Adult Stress Enhances Adrenergic Signaling to Advance Visceral Hypersensitivity.Neuroscience bulletin · 2019Article
- International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of HPharmacological reviews · 2017Review
- α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats.Journal of pain research · 2017Article
- Neonatal Colonic Inflammation Increases Spinal Transmission and Cystathionine β-Synthetase Expression in Spinal Dorsal Horn of Rats with Visceral Hypersensitivity.Frontiers in pharmacology · 2017Article
- Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin.Frontiers in systems neuroscience · 2017Review
- Inhibition of cystathionine β-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation.Scientific reports · 2016Article
- A Genome-Wide Association Study Identifies a Novel Locus for Bortezomib-Induced Peripheral Neuropathy in European Patients with Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes.Journal of neurogastroenterology and motility · 2016Article
- Sensitization of P2X3 receptors by cystathionine β-synthetase mediates persistent pain hypersensitivity in a rat model of lumbar disc herniation.Molecular pain · 2015Article
- Upregulation of nav1.7 through high salt loading: (mol pain 2013;9:39).Journal of neurogastroenterology and motility · 2014Article
- Adrenergic β2-receptors mediates visceral hypersensitivity induced by heterotypic intermittent stress in rats.PloS one · 2014Article
- Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: role of TRPA1 receptors.American journal of physiology. Regulatory, integrative and comparative physiology · 2013Article
- PKCγ receptor mediates visceral nociception and hyperalgesia following exposure to PTSD-like stress in the spinal cord of rats.Molecular pain · 2013Article
- Promoted interaction of nuclear factor-κB with demethylated cystathionine-β-synthetase gene contributes to gastric hypersensitivity in diabetic rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHydrogen sulfide (H₂S) functions as a neuromodulator, but whether it modulates visceral pain is not well known. This study was designed to determine the role for the endogenous H₂S producing enzyme cystathionine β-synthetase (CBS) and cystathionine γ-lyase (CSE) in a validated rat model of visceral hyperalgesia (VH).
methodsVH was induced by nine-day heterotypic intermittent stress (HIS). Abdominal withdrawal reflex (AWR) scores were determined by measuring the visceromoter responses to colorectal distension (CRD). Dorsal root ganglia (DRG) neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate) into the colon wall. Patch clamp recording techniques were employed to examine excitability and sodium channel currents of colon specific DRG neurons. Tissues from colon related thoracolumbar DRGs were analyzed for CBS, CSE and sodium channel expression.
resultsHIS significantly increased the visceromotor responses to CRD in association with an upregulated expression of CBS not CSE proteins in colon related DRGs. Administration of O-(Carboxymethyl)hydroxylamine hemihydrochloride (AOAA), an inhibitor of CBS, attenuated the AWR scores in HIS-treated rats, in a dose dependent fashion. In contrast, AOAA did not produce any effect on AWR scores in healthy control rats. AOAA reversed the potentiation of sodium channel current densities of colon specific DRG neurons of HIS rats. To further confirm the role for CBS-H₂S signaling, NaHS was used to mimic the production of H₂S by CBS. Application of NaHS significantly enhanced neuronal excitability and potentiated sodium channel current densities of colon DRG neurons from healthy control rats. Furthermore, AOAA reversed the upregulation of Na(V)1.7 and Na(V)1.8 in colon related DRGs of HIS rats.
conclusionOur results suggest that upregulation of CBS expression might play an important role in developing VH via sensitization of sodium channels in peripheral nociceptors, thus identifying a specific neurobiological target for the treatment of VH in functional bowel syndromes.
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