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ARTICLE, Behavioral/Systems

The Involvement of the Tetrodotoxin-Resistant Sodium Channel Nav1.8 (PN3/SNS) in a Rat Model of Visceral Pain

Naoki Yoshimura, Satoshi Seki, Sanja D. Novakovic, Elda Tzoumaka, Vickie L. Erickson, Kristin A. Erickson, Michael B. Chancellor and William C. de Groat
Journal of Neuroscience 1 November 2001, 21 (21) 8690-8696; DOI: https://doi.org/10.1523/JNEUROSCI.21-21-08690.2001
Naoki Yoshimura
1Departments of Urology and
2Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and
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Satoshi Seki
2Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and
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Sanja D. Novakovic
3Neurobiology Unit, Roche Bioscience, Palo Alto, California 94304
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Elda Tzoumaka
3Neurobiology Unit, Roche Bioscience, Palo Alto, California 94304
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Vickie L. Erickson
2Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and
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Kristin A. Erickson
2Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and
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Michael B. Chancellor
1Departments of Urology and
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William C. de Groat
2Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and
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    Fig. 1.

    Effects of intravesical infusion of 0.1% acetic acid on cystometrograms in rats treated with mismatch or antisense oligodeoxynucleotide (ODN) for Nav1.8 sodium channels. Note that in an antisense-treated rat, acetic acid-induced bladder hyperactivity was suppressed.

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    Fig. 2.

    Effects of intravesical infusion of acetic acid on intercontraction intervals (ICI) in rats treated with mismatch (n = 8) or antisense ODN (n = 8). Note that in antisense ODN-treated rats, the ICI in the control period is significantly longer and a reduction in the ICI after acetic acid infusion is significantly smaller, when compared with mismatch ODN-treated rats. *p < 0.05, **p < 0.01.

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    Fig. 3.

    Effects of Nav1.8 antisense ODN on c-fos expression in the L6 spinal cord after intravesical infusion of acetic acid. A, Photomicrographs of Fos staining in transverse sections of the L6 spinal cord from rats treated with mismatch (left panel) and antisense (right panel) ODN. B, Histograms of the number of Fos-positive cells after intravesical acetic acid infusion.DCM, Dorsal commissure; DH, dorsal horn;SPN, sacral parasympathetic nucleus; CC, central canal. *p < 0.01.

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    Fig. 4.

    Immunolabeling of Nav1.8 TTX-resistant sodium channels in L6 DRG. A, Photomicrographs of Nav1.8 immunostaining in rat treated with mismatch (left panel) or antisense (right panel) ODN. Scale bar, 50 μm. B, Averaged Nav1.8 labeling intensity in L6 DRG neurons with small, medium, and large cross-sectional somal areas. Note that labeling intensity is greater in small-sized neurons and significantly reduced after antisense treatment in small- to medium-sized neurons. *p < 0.01.

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    Fig. 5.

    Effects of Nav1.8 antisense ODN on TTX-resistant sodium currents in bladder afferent neurons.A, Superimposed traces of TTX-resistant sodium currents elicited by depolarizing pulses to 10 mV from the holding potential of −60 mV in neurons from rats treated with mismatch and antisense ODN.B, Maximum conductance densities of TTX-resistant sodium currents. In rats treated with antisense ODN, the conductance density of TTX-resistant sodium currents (n = 15 neurons) was significantly smaller compared with rats with mismatch ODN treatment (n = 15 neurons). *p< 0.05.

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The Journal of Neuroscience: 21 (21)
Journal of Neuroscience
Vol. 21, Issue 21
1 Nov 2001
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The Involvement of the Tetrodotoxin-Resistant Sodium Channel Nav1.8 (PN3/SNS) in a Rat Model of Visceral Pain
Naoki Yoshimura, Satoshi Seki, Sanja D. Novakovic, Elda Tzoumaka, Vickie L. Erickson, Kristin A. Erickson, Michael B. Chancellor, William C. de Groat
Journal of Neuroscience 1 November 2001, 21 (21) 8690-8696; DOI: 10.1523/JNEUROSCI.21-21-08690.2001

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The Involvement of the Tetrodotoxin-Resistant Sodium Channel Nav1.8 (PN3/SNS) in a Rat Model of Visceral Pain
Naoki Yoshimura, Satoshi Seki, Sanja D. Novakovic, Elda Tzoumaka, Vickie L. Erickson, Kristin A. Erickson, Michael B. Chancellor, William C. de Groat
Journal of Neuroscience 1 November 2001, 21 (21) 8690-8696; DOI: 10.1523/JNEUROSCI.21-21-08690.2001
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Keywords

  • dorsal root ganglion
  • tetrodotoxin
  • Nav1.8 sodium channels
  • urinary bladder
  • acetic acid
  • inflammation
  • antisense oligodeoxynucleotide

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