Spinal neurokinin NK1 receptor down-regulation and antinociception: Effects of spinal NK1 receptor antisense oligonucleotides and nk1 receptor occupancy

Xiao Ying Hua, Ping Chen, Erika Polgar, I. Nagy, Martin Marsala, Elsa Phillips, Laura Wollaston, Laszlo Urban, Tony L. Yaksh, Michael Webb

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

To define the effects of antisense oligonucleotides on spinal neurokinin 1 (NK1) receptor function in nociceptive processing, several antisense oligonucleotides directed against the NK1 receptor mRNA were intrathecally injected into rats via an implanted catheter, and their effect on the behavioural response to formalin injected into the paw was assessed. We observed that there was no significant reduction of pain behaviour or immunostaining of spinal NK1 receptors after repeated daily intrathecal treatment with an antisense oligonucleotide. However, spinal application of substance P (SP) in the antisense oligonucleotide-treated animals resulted in a profound and long-lasting reduction in the behavioural response to formalin injection, and a parallel reduction in the NK1 receptor immunoreactivity normally observed in spinal dorsal horn. Intrathecal SP in the control groups, i.e., rats treated with an oligonucleotide containing four mismatched bases, the corresponding sense oligonucleotide, a mixture of the sense and the antisense oligonucleotides, in each case had no effect. The effects of SP were blocked by NK1 receptor antagonists and were not mimicked by NMDA. The mechanism underlying these effects is not clear. It may be due to partial degradation of the internalised receptors, which cannot be replaced by newly synthesised receptors because of the action of the NK1 antisense oligonucleotide.

Original languageEnglish
Pages (from-to)688-698
Number of pages11
JournalJournal of Neurochemistry
Volume70
Issue number2
Publication statusPublished - Feb 1998

Fingerprint

Neurokinin-1 Receptors
Antisense Oligonucleotides
Down-Regulation
Substance P
Oligonucleotides
Formaldehyde
Rats
Neurokinin-1 Receptor Antagonists
Catheters
N-Methylaspartate
Animals
Pain
Degradation
Control Groups
Messenger RNA
Injections
Processing

Keywords

  • Antinociception
  • Antisense oligonucleotide
  • NK1 receptor
  • Spinal cord
  • Substance P

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Spinal neurokinin NK1 receptor down-regulation and antinociception : Effects of spinal NK1 receptor antisense oligonucleotides and nk1 receptor occupancy. / Hua, Xiao Ying; Chen, Ping; Polgar, Erika; Nagy, I.; Marsala, Martin; Phillips, Elsa; Wollaston, Laura; Urban, Laszlo; Yaksh, Tony L.; Webb, Michael.

In: Journal of Neurochemistry, Vol. 70, No. 2, 02.1998, p. 688-698.

Research output: Contribution to journalArticle

Hua, XY, Chen, P, Polgar, E, Nagy, I, Marsala, M, Phillips, E, Wollaston, L, Urban, L, Yaksh, TL & Webb, M 1998, 'Spinal neurokinin NK1 receptor down-regulation and antinociception: Effects of spinal NK1 receptor antisense oligonucleotides and nk1 receptor occupancy', Journal of Neurochemistry, vol. 70, no. 2, pp. 688-698.
Hua, Xiao Ying ; Chen, Ping ; Polgar, Erika ; Nagy, I. ; Marsala, Martin ; Phillips, Elsa ; Wollaston, Laura ; Urban, Laszlo ; Yaksh, Tony L. ; Webb, Michael. / Spinal neurokinin NK1 receptor down-regulation and antinociception : Effects of spinal NK1 receptor antisense oligonucleotides and nk1 receptor occupancy. In: Journal of Neurochemistry. 1998 ; Vol. 70, No. 2. pp. 688-698.
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