Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.26.4 (
RNase H
)
2,751
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To examine the role of the vanilloid receptor
TRPV1
in neuropathic pain, we assessed the effects of the receptor antagonist thioxo-BCTC and antisense oligonucleotides against the
TRPV1
mRNA in a rat model of spinal nerve ligation. In order to identify accessible sites on the mRNA of
TRPV1
, the
RNase H
assay was used, leading to the successful identification of binding sites for antisense oligonucleotides. Cotransfection studies using Cos-7 cells were employed to identify the most effective antisense oligonucleotide efficiently inhibiting the expression of a fusion protein consisting of
TRPV1
and the green fluorescent protein in a specific and concentration-dependent manner. In an in vivo rat model of spinal nerve ligation, intravenous application of the
TRPV1
antagonist thioxo-BCTC reduced mechanical hypersensitivity yielding an ED(50) value of 10.6mg/kg. Intrathecal administration of the antisense oligonucleotide against
TRPV1
, but not the mismatch oligonucleotide or a vehicle control, reduced mechanical hypersensitivity in rats with spinal nerve ligation in a similar manner. Immunohistochemical analysis revealed neuropathy- and antisense-associated regulation of
TRPV1
protein expression in spinal cord and dorsal root ganglia. Our data demonstrate comparative analgesic effects of a
TRPV1
anatagonist and a rationally designed
TRPV1
antisense oligonucleotide in a spinal nerve ligation model of neuropathic pain and thus, lend support to the validation of
TRPV1
as a promising target for the treatment of neuropathic pain.
...
PMID:Antinociceptive effect of antisense oligonucleotides against the vanilloid receptor VR1/TRPV1. 1704 2
