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Open Access 01-12-2012 | Research

Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation

Authors: Lin Li, Ruihua Xie, Shufen Hu, Yongmeng Wang, Tianzhu Yu, Ying Xiao, Xinghong Jiang, Jianguo Gu, Chuang-Ying Hu, Guang-Yin Xu

Published in: Molecular Pain | Issue 1/2012

Abstract

Background

Irritable bowel syndrome (IBS) is characterized by chronic visceral hyperalgesia (CVH) that manifested with persistent or recurrent abdominal pain and altered bowel movement. However, the pathogenesis of the CVH remains unknown. The aim of this study was to investigate roles of endogenous hydrogen sulfide (H₂S) producing enzyme cystathionine beta-synthetase (CBS) and p65 nuclear factor-kappa B subunits in CVH.

Results

CVH was induced by neonatal maternal deprivation (NMD) in male rats on postnatal days 2–15 and behavioral experiments were conducted at the age of 7–15 weeks. NMD significantly increased expression of CBS in colon-innervating DRGs from the 7^th to 12^th week. This change in CBS express is well correlated with the time course of enhanced visceromoter responses to colorectal distention (CRD), an indicator of visceral pain. Administration of AOAA, an inhibitor of CBS, produced a dose-dependent antinociceptive effect on NMD rats while it had no effect on age-matched healthy control rats. AOAA also reversed the enhanced neuronal excitability seen in colon-innervating DRGs. Application of NaHS, a donor of H₂S, increased excitability of colon-innervating DRG neurons acutely dissociated from healthy control rats. Intrathecal injection of NaHS produced an acute visceral hyperalgesia. In addition, the content of p65 in nucleus was remarkably higher in NMD rats than that in age-matched controls. Intrathecal administration of PDTC, an inhibitor of p65, markedly reduced expression of CBS and attenuated nociceptive responses to CRD.

Conclusion

The present results suggested that upregulation of CBS expression, which is mediated by activation of p65, contributes to NMD-induced CVH. This pathway might be a potential target for relieving CVH in patients with IBS.

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Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Muller-Lissner SA: Functional bowel disorders and functional abdominal pain. Gut 1999,45(2):II43–47. 10.1136/gut.45.2008.ii43PubMedCentralPubMed

Coutinho SV, Plotsky PM, Sablad M, Miller JC, Zhou H, Bayati AI, McRoberts JA, Mayer EA: Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. Am J Physiol Gastrointest Liver Physiol 2002, 282: G307–316.CrossRefPubMed

Gareau MG, Jury J, Yang PC, MacQueen G, Perdue MH: Neonatal maternal separation causes colonic dysfunction in rat pups including impaired host resistance. Pediatr Res 2006, 59: 83–88. 10.1203/01.pdr.0000190577.62426.45CrossRefPubMed

Hill OW, Price JS: Childhood bereavement and adult depression. Br J Psychiatry 1967, 113: 743–751. 10.1192/bjp.113.500.743CrossRefPubMed

Lee AT, Shah JJ, Li L, Cheng Y, Moore PK, Khanna S: A nociceptive-intensity-dependent role for hydrogen sulphide in the formalin model of persistent inflammatory pain. Neuroscience 2008, 152: 89–96. 10.1016/j.neuroscience.2007.11.052CrossRefPubMed

Maeda Y, Aoki Y, Sekiguchi F, Matsunami M, Takahashi T, Nishikawa H, Kawabata A: Hyperalgesia induced by spinal and peripheral hydrogen sulfide: evidence for involvement of Cav3.2 T-type calcium channels. Pain 2009, 142: 127–132. 10.1016/j.pain.2008.12.021CrossRefPubMed

Kawabata A, Ishiki T, Nagasawa K, Yoshida S, Maeda Y, Takahashi T, Sekiguchi F, Wada T, Ichida S, Nishikawa H: Hydrogen sulfide as a novel nociceptive messenger. Pain 2007, 132: 74–81. 10.1016/j.pain.2007.01.026CrossRefPubMed

Xu GY, Winston JH, Shenoy M, Zhou S, Chen JD, Pasricha PJ: The endogenous hydrogen sulfide producing enzyme cystathionine-beta synthase contributes to visceral hypersensitivity in a rat model of irritable bowel syndrome. Mol Pain 2009, 5: 44. 10.1186/1744-8069-5-44PubMedCentralCrossRefPubMed

Martin GR, McKnight GW, Dicay MS, Coffin CS, Ferraz JG, Wallace JL: Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract. Dig Liver Dis 2010, 42: 103–109. 10.1016/j.dld.2009.05.016CrossRefPubMed

10.

Wu LC, Goettl VM, Madiai F, Hackshaw KV, Hussain SR: Reciprocal regulation of nuclear factor kappa B and its inhibitor ZAS3 after peripheral nerve injury. BMC Neurosci 2006, 7: 4. 10.1186/1471-2202-7-4PubMedCentralCrossRefPubMed

11.

Fu ES, Zhang YP, Sagen J, Candiotti KA, Morton PD, Liebl DJ, Bethea JR, Brambilla R: Transgenic inhibition of glial NF-kappa B reduces pain behavior and inflammation after peripheral nerve injury. Pain 2010, 148: 509–518. 10.1016/j.pain.2010.01.001PubMedCentralCrossRefPubMed

12.

O'Rielly DD, Loomis CW: Spinal nerve ligation-induced activation of nuclear factor kappaB is facilitated by prostaglandins in the affected spinal cord and is a critical step in the development of mechanical allodynia. Neuroscience 2008, 155: 902–913. 10.1016/j.neuroscience.2008.04.077CrossRefPubMed

13.

Wei XH, Zang Y, Wu CY, Xu JT, Xin WJ, Liu XG: Peri-sciatic administration of recombinant rat TNF-alpha induces mechanical allodynia via upregulation of TNF-alpha in dorsal root ganglia and in spinal dorsal horn: the role of NF-kappa B pathway. Exp Neurol 2007, 205: 471–484. 10.1016/j.expneurol.2007.03.012CrossRefPubMed

14.

Chou CW, Wong GT, Lim G, Wang S, Irwin MG, Mao J: Spatiotemporal pattern of concurrent spinal and supraspinal NF-kappaB expression after peripheral nerve injury. J Pain 2011, 12: 13–21. 10.1016/j.jpain.2010.03.018PubMedCentralCrossRefPubMed

15.

Ma W, Bisby MA: Increased activation of nuclear factor kappa B in rat lumbar dorsal root ganglion neurons following partial sciatic nerve injuries. Brain Res 1998, 797: 243–254. 10.1016/S0006-8993(98)00380-1CrossRefPubMed

16.

Bethea JR, Castro M, Keane RW, Lee TT, Dietrich WD, Yezierski RP: Traumatic spinal cord injury induces nuclear factor-kappaB activation. J Neurosci 1998, 18: 3251–3260.PubMed

17.

Yang L, Tao LY, Chen XP: Roles of NF-kappaB in central nervous system damage and repair. Neurosci Bull 2007, 23: 307–313. 10.1007/s12264-007-0046-6CrossRefPubMed

18.

Zelenka M, Schafers M, Sommer C: Intraneural injection of interleukin-1beta and tumor necrosis factor-alpha into rat sciatic nerve at physiological doses induces signs of neuropathic pain. Pain 2005, 116: 257–263. 10.1016/j.pain.2005.04.018CrossRefPubMed

19.

Tegeder I, Niederberger E, Schmidt R, Kunz S, Guhring H, Ritzeler O, Michaelis M, Geisslinger G: Specific Inhibition of IkappaB kinase reduces hyperalgesia in inflammatory and neuropathic pain models in rats. J Neurosci 2004, 24: 1637–1645. 10.1523/JNEUROSCI.3118-03.2004CrossRefPubMed

20.

Laughlin TM, Bethea JR, Yezierski RP, Wilcox GL: Cytokine involvement in dynorphin-induced allodynia. Pain 2000, 84: 159–167. 10.1016/S0304-3959(99)00195-5CrossRefPubMed

21.

Pan YD, Guo QL, Wang E, Ye Z, He ZH, Zou WY, Cheng ZG, Wang YJ: Intrathecal infusion of pyrrolidine dithiocarbamate for the prevention and reversal of neuropathic pain in rats using a sciatic chronic constriction injury model. Reg Anesth Pain Med 2010, 35: 231–237. 10.1097/AAP.0b013e3181df245bCrossRefPubMed

22.

Zang Y, He XH, Xin WJ, Pang RP, Wei XH, Zhou LJ, Li YY, Liu XG: Inhibition of NF-kappaB prevents mechanical allodynia induced by spinal ventral root transection and suppresses the re-expression of Nav1.3 in DRG neurons in vivo and in vitro. Brain Res 2010, 1363: 151–158.CrossRefPubMed

23.

Baeuerle PA, Baichwal VR: NF-kappa B as a frequent target for immunosuppressive and anti-inflammatory molecules. Adv Immunol 1997, 65: 111–137.CrossRefPubMed

24.

Barnes PJ, Karin M: Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997, 336: 1066–1071. 10.1056/NEJM199704103361506CrossRefPubMed

25.

Zhang J, Li L, Lu Q, Xiao R, Wen H, Yan K, Li Y, Zhou Y, Su Y, Zhang G, et al.: Acute stress enhances contact dermatitis by promoting nuclear factor-kappaB DNA-binding activity and interleukin-18 expression in mice. J Dermatol 2010, 37: 512–521. 10.1111/j.1346-8138.2009.00771.xCrossRefPubMed

26.

Alvarez S, Blanco A, Fresno M, Munoz-Fernandez MA: Nuclear factor-kappaB activation regulates cyclooxygenase-2 induction in human astrocytes in response to CXCL12: role in neuronal toxicity. J Neurochem 2010, 113: 772–783. 10.1111/j.1471-4159.2010.06646.xCrossRefPubMed

27.

Sun T, Luo J, Jia M, Li H, Li K, Fu Z: Small interfering RNA-mediated knockdown of NF-kappaBp65 attenuates neuropathic pain following peripheral nerve injury in rats. Eur J Pharmacol 2012, 682: 79–85. 10.1016/j.ejphar.2012.02.017CrossRefPubMed

28.

Bian ZX, Zhang M, Han QB, Xu HX, Sung JJ: Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats. World J Gastroenterol 2010, 16: 837–845.PubMedCentralPubMed

29.

Al-Chaer ED, Kawasaki M, Pasricha PJ: A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. Gastroenterology 2000, 119: 1276–1285. 10.1053/gast.2000.19576CrossRefPubMed

30.

Xu GY, Shenoy M, Winston JH, Mittal S, Pasricha PJ: P2X receptor-mediated visceral hyperalgesia in a rat model of chronic visceral hypersensitivity. Gut 2008, 57: 1230–1237. 10.1136/gut.2007.134221CrossRefPubMed

31.

Xu GY, Huang LY: Peripheral inflammation sensitizes P2X receptor-mediated responses in rat dorsal root ganglion neurons. J Neurosci 2002, 22: 93–102.PubMed

32.

Hu S, Yang J, Li L, Zhu L, Zhou Y, Xiao Y, Xu GY: Upregulation of Endogenous Cystathionine-beta-Synthase Contributes to Visceral Hypersensitivity in Adult Rats Following Neonatal Maternal Deprivation. DDW abstract 2012,142(5 Supplement 1):S-702. Mo1861

33.

Winston JH, Xu GY, Sarna SK: Adrenergic stimulation mediates visceral hypersensitivity to colorectal distension following heterotypic chronic stress. Gastroenterology 2010, 138: 294–304. e293 10.1053/j.gastro.2009.09.054PubMedCentralCrossRefPubMed

34.

Berti-Mattera LN, Larkin B, Hourmouzis Z, Kern TS, Siegel RE: NF-kappaB subunits are differentially distributed in cells of lumbar dorsal root ganglia in naive and diabetic rats. Neurosci Lett 2011, 490: 41–45. 10.1016/j.neulet.2010.12.022PubMedCentralCrossRefPubMed

35.

Luo JL, Qin HY, Wong CK, Tsang SY, Huang Y, Bian ZX: Enhanced excitability and down-regulated voltage-gated potassium channels in colonic drg neurons from neonatal maternal separation rats. J Pain 2011, 12: 600–609. 10.1016/j.jpain.2010.11.005CrossRefPubMed

36.

Ren TH, Wu J, Yew D, Ziea E, Lao L, Leung WK, Berman B, Hu PJ, Sung JJ: Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2007, 292: G849–856.CrossRefPubMed

37.

Kaneko H, Imamura H, Konagaya T: [Visceral hypersensitivity]. Nihon Rinsho 2006, 64: 1446–1451.PubMed

38.

Xu GY, Winston JH, Chen JD: Electroacupuncture attenuates visceral hyperalgesia and inhibits the enhanced excitability of colon specific sensory neurons in a rat model of irritable bowel syndrome. Neurogastroenterol Motil 2009, 21: 1302-e1125. 10.1111/j.1365-2982.2009.01354.xCrossRefPubMed

39.

Kataoka H, Horiyama S, Yamaki M, Oku H, Ishiguro K, Katagi T, Takayama M, Semma M, Ito Y: Anti-inflammatory and anti-allergic activities of hydroxylamine and related compounds. Biol Pharm Bull 2002, 25: 1436–1441. 10.1248/bpb.25.1436CrossRefPubMed

40.

Qi F, Zhou Y, Xiao Y, Tao J, Gu J, Jiang X, Xu G-Y: Promoter demethylation of cystathionine-b-synthetase gene contributes to inflammatory pain in rats. Pain 2012. 10.1016/j.pain.2012.1007.1031

41.

Gushchina SV, Volkova OV, Krugliakov PP, Magoulas CB: [Transcriptional activity of nuclear factor kappa B (NFkappaB) in posttraumatic sensory neurons (histochemical study)]. Morfologiia 2010, 137: 18–22.PubMed

Title: Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation
Authors: Lin Li
Ruihua Xie
Shufen Hu
Yongmeng Wang
Tianzhu Yu
Ying Xiao
Xinghong Jiang
Jianguo Gu
Chuang-Ying Hu
Guang-Yin Xu
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2012
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-8-89

2024 ASCO Annual Meeting

Springer Medicine

Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation

Abstract

Background

Results

Conclusion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Results

Conclusion

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