Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons: A strategy to increase opioid antinociception

Y. Xu, Yanping Gu, G. Y. Xu, Ping Wu, G. W. Li, Li-Yen Huang

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

To develop a genetic approach for the treatment of pain, we introduced a recombinant adeno-associated viral (rAAV) vector containing the cDNA for the μ-opioid receptor (μOR) into primary afferent neurons in dorsal root ganglia (DRGs) of rats, which resulted in a long-lasting (>6 months) increase in μOR expression in DRG neurons. The increase greatly potentiated the antinociceptive effects of morphine in rAAV-μOR-infected rats with and without inflammation. Perforated patch recordings indicated that the efficacy and potency of opioid inhibition of voltage-dependent Ca2+ channels were enhanced in infected neurons, which may underlie the increase in opiate efficacy. These data suggest that transfer of opioid receptor genes into DRG cells with rAAV vectors may offer a new therapeutic strategy for pain management.

Original languageEnglish (US)
Pages (from-to)6204-6209
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number10
DOIs
StatePublished - May 13 2003

Fingerprint

Opioid Receptors
Sensory Receptor Cells
Opioid Analgesics
Spinal Ganglia
Genes
Opiate Alkaloids
Neurons
Afferent Neurons
Pain Management
Morphine
Complementary DNA
Inflammation
Pain
Transfer (Psychology)
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{57cf9ba0243c4f25a41f463027dbbeb2,
title = "Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons: A strategy to increase opioid antinociception",
abstract = "To develop a genetic approach for the treatment of pain, we introduced a recombinant adeno-associated viral (rAAV) vector containing the cDNA for the μ-opioid receptor (μOR) into primary afferent neurons in dorsal root ganglia (DRGs) of rats, which resulted in a long-lasting (>6 months) increase in μOR expression in DRG neurons. The increase greatly potentiated the antinociceptive effects of morphine in rAAV-μOR-infected rats with and without inflammation. Perforated patch recordings indicated that the efficacy and potency of opioid inhibition of voltage-dependent Ca2+ channels were enhanced in infected neurons, which may underlie the increase in opiate efficacy. These data suggest that transfer of opioid receptor genes into DRG cells with rAAV vectors may offer a new therapeutic strategy for pain management.",
author = "Y. Xu and Yanping Gu and Xu, {G. Y.} and Ping Wu and Li, {G. W.} and Li-Yen Huang",
year = "2003",
month = "5",
day = "13",
doi = "10.1073/pnas.0930324100",
language = "English (US)",
volume = "100",
pages = "6204--6209",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "10",

}

TY - JOUR

T1 - Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons

T2 - A strategy to increase opioid antinociception

AU - Xu, Y.

AU - Gu, Yanping

AU - Xu, G. Y.

AU - Wu, Ping

AU - Li, G. W.

AU - Huang, Li-Yen

PY - 2003/5/13

Y1 - 2003/5/13

N2 - To develop a genetic approach for the treatment of pain, we introduced a recombinant adeno-associated viral (rAAV) vector containing the cDNA for the μ-opioid receptor (μOR) into primary afferent neurons in dorsal root ganglia (DRGs) of rats, which resulted in a long-lasting (>6 months) increase in μOR expression in DRG neurons. The increase greatly potentiated the antinociceptive effects of morphine in rAAV-μOR-infected rats with and without inflammation. Perforated patch recordings indicated that the efficacy and potency of opioid inhibition of voltage-dependent Ca2+ channels were enhanced in infected neurons, which may underlie the increase in opiate efficacy. These data suggest that transfer of opioid receptor genes into DRG cells with rAAV vectors may offer a new therapeutic strategy for pain management.

AB - To develop a genetic approach for the treatment of pain, we introduced a recombinant adeno-associated viral (rAAV) vector containing the cDNA for the μ-opioid receptor (μOR) into primary afferent neurons in dorsal root ganglia (DRGs) of rats, which resulted in a long-lasting (>6 months) increase in μOR expression in DRG neurons. The increase greatly potentiated the antinociceptive effects of morphine in rAAV-μOR-infected rats with and without inflammation. Perforated patch recordings indicated that the efficacy and potency of opioid inhibition of voltage-dependent Ca2+ channels were enhanced in infected neurons, which may underlie the increase in opiate efficacy. These data suggest that transfer of opioid receptor genes into DRG cells with rAAV vectors may offer a new therapeutic strategy for pain management.

UR - http://www.scopus.com/inward/record.url?scp=0038623685&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038623685&partnerID=8YFLogxK

U2 - 10.1073/pnas.0930324100

DO - 10.1073/pnas.0930324100

M3 - Article

C2 - 12719538

AN - SCOPUS:0038623685

VL - 100

SP - 6204

EP - 6209

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 10

ER -