title: Acute colitis induces neurokinin 1 receptor internalization in the rat lumbosacral spinal cord.
abstract: Substance P (SP) and its receptor, the neurokinin 1 receptor (NK1R), play important roles in transmitting and regulating somatosensory nociceptive information. However, their roles in visceral nociceptive transmission and regulation remain to be elucidated. In the previous study, moderate SP immunoreactive (SP-ir) terminals and NK1R-ir neurons were observed in the dorsal commissural nucleus (DCN) of the lumbosacral spinal cord. Thus we hypothesized that the SP-NK1R system is involved in visceral pain transmission and control within the DCN. The acute visceral pain behaviors, the colon histological changes and the temporal and spatial changes of NK1R-ir structures and Fos expression in the neurons of the DCN were observed in rats following lower colon instillation with 5% formalin. The formalin instillation induced significant acute colitis as revealed by the histological changes in the colon. NK1R internalization in the DCN was obvious at 8 min. It reached a peak (75.3%) at 30 min, began to decrease at 90 min (58.1%) and finally reached the minimum (19.7%) at 3 h after instillation. Meanwhile, formalin instillation induced a biphasic visceral pain response as well as a strong expression of Fos protein in the nuclei of neurons in the DCN. Finally, intrathecal treatment with the NK1R antagonist L732138 attenuated the NK1R internalization, Fos expression and visceral nociceptive responses. The present results suggest that the visceral nociceptive information arising from inflamed pelvic organs, such as the lower colon, might be mediated by the NK1R-ir neurons in the DCN of the lumbosacral spinal cord.
authors.affiliation: Department of Anatomy, Histology, Embryology & K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Pei
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Sheng-Xi
authors.initials: SX
authors.lastname: Wu
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000208:Acute Disease; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005557:Formaldehyde; D015870:Gene Expression / Q000187:drug effects; D008161:Lumbosacral Region / Q000294:innervation / Q000503:physiopathology; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D059225:Nociception / Q000187:drug effects*; D059226:Nociceptive Pain / Q000378:metabolism* / Q000503:physiopathology; D021381:Protein Transport / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000235:genetics / Q000378:metabolism; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D016760:Proto-Oncogene Proteins c-fos; D018040:Receptors, Neurokinin-1; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D005557:Formaldehyde; D013373:Substance P; D014364:Tryptophan
references.citation: Neuroscience. 2009 Jun 30;161(2):538-53
references.pmid: 19336248
references.citation: Pain. 1990 May;41(2):167-234
references.pmid: 2195438
references.citation: J Neurosci. 2002 May 15;22(10):4103-13
references.pmid: 12019329
references.citation: J Neurosci Methods. 2000 Jul 31;100(1-2):71-8
references.pmid: 11040368
references.citation: Neurosci Lett. 1998 Apr 24;246(2):73-6
references.pmid: 9627183
references.citation: Pain. 2002 Feb;95(3):277-285
references.pmid: 11839427
references.citation: Pain. 2001 Jun;92(3):335-342
references.pmid: 11376906
references.citation: J Neurosci. 1999 Sep 1;19(17):7670-8
references.pmid: 10460273
references.citation: Neuroscience. 1998 Dec;87(4):925-31
references.pmid: 9759980
references.citation: Neurosci Lett. 1995 Sep 29;198(2):139-42
references.pmid: 8592640
references.citation: Nature. 1997 Apr 17;386(6626):721-4
references.pmid: 9109489
references.citation: Neuroscience. 2005;131(1):209-17
references.pmid: 15680704
references.citation: Neuroscience. 2010 Mar 31;166(3):924-34
references.pmid: 20074620
references.citation: Pain Physician. 2012 Jul-Aug;15(4):311-26
references.pmid: 22828685
references.citation: Eur J Neurosci. 2001 Aug;14(3):426-34
references.pmid: 11553293
references.citation: Gastroenterology. 2006 May;130(6):1729-42
references.pmid: 16697737
references.citation: Somatosens Mot Res. 1998;15(1):5-12
references.pmid: 9583573
references.citation: Int Immunopharmacol. 2003 Nov;3(12):1563-8
references.pmid: 14555281
references.citation: Prog Brain Res. 1995;104:283-98
references.pmid: 8552774
references.citation: Brain Res. 1988 May 31;450(1-2):153-69
references.pmid: 3401708
references.citation: Neuroscience. 2003;116(2):565-72
references.pmid: 12559111
references.citation: J Comp Neurol. 1981 Sep 20;201(3):415-40
references.pmid: 7276258
references.citation: J Chem Neuroanat. 2004 Jul;27(4):251-66
references.pmid: 15261332
references.citation: Open Pain J. 2009 Jan 1;2:11-17
references.pmid: 19898681
references.citation: Science. 1995 Jun 16;268(5217):1629-32
references.pmid: 7539937
references.citation: Neuroscience. 2011 Mar 17;177:308-20
references.pmid: 21215796
references.citation: J Pain. 2002 Feb;3(1):3-11
references.pmid: 14622848
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11086-91
references.pmid: 10995467
references.citation: J Neurosci. 1997 Aug 1;17(15):5921-7
references.pmid: 9221788
references.citation: Eur J Pharmacol. 2011 Sep 30;667(1-3):169-74
references.pmid: 21645509
references.citation: Pain. 1994 Jun;57(3):327-334
references.pmid: 7524010
references.citation: Proc Natl Acad Sci U S A. 1988 Oct;85(20):7820-4
references.pmid: 2459717
references.citation: Neuroscience. 2003;118(2):535-45
references.pmid: 12699788
references.citation: Brain Res. 2002 Jul 19;944(1-2):239-47
references.pmid: 12106686
references.citation: Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2622-6
references.pmid: 7535928
references.citation: Neuroscience. 2000;98(2):345-52
references.pmid: 10854767
references.citation: J Neurosci. 1997 Oct 15;17(20):8049-60
references.pmid: 9315923
references.citation: J Comp Neurol. 1984 Jun 20;226(2):238-45
references.pmid: 6736301
references.citation: Brain Res Bull. 1993;30(3-4):239-43
references.pmid: 7681350
references.citation: Brain Res. 2004 Jun 4;1010(1-2):117-26
references.pmid: 15126124
references.citation: Pain. 2003 Jul;104(1-2):249-57
references.pmid: 12855335
references.citation: Cancers (Basel). 2010 Apr 20;2(2):611-23
references.pmid: 24281084
references.citation: Brain Res Bull. 1998;45(1):1-8
references.pmid: 9434195
references.citation: Science. 1997 Oct 10;278(5336):275-9
references.pmid: 9323204
references.citation: Pharmacol Biochem Behav. 2003 Mar;74(4):1005-13
references.pmid: 12667916
references.citation: J Neurosci. 2006 Nov 15;26(46):12033-42
references.pmid: 17108177