Intrathecal PLC(β3) oligodeoxynucleotides antisense potentiates acute morphine efficacy and attenuates chronic morphine tolerance
- PMID: 22771399
- DOI: 10.1016/j.brainres.2012.06.030
Intrathecal PLC(β3) oligodeoxynucleotides antisense potentiates acute morphine efficacy and attenuates chronic morphine tolerance
Abstract
Morphine is a mainstay for chronic pain treatment, but its efficacy has been hampered by physical tolerance. The underlying mechanism for chronic morphine induced tolerance is complicated and not well understood. PLC(β3) is regarded as an important factor in the morphine tolerance signal pathway. In this study, we determined intrathecal (i.t.) administration of an antisense oligodeoxynucleotide (ODN) of PLC(β3) could quicken the on-set antinociceptive efficacy of acute morphine treatment and prolong the maximum effect up to 4h. The antisense could also attenuate the development of morphine-induced tolerance and left shift the ED50 after 7 day of coadministration with morphine. These results probably were contributed by the PLC(β3) antisense ODN as they successfully knocked down protein expression levels and reduced activity of PLC(β3) in spinal cord in rats. The mismatch group had no such effects. The results confirmed the important involvement of PLC(β3) in both acute morphine efficacy and chronic morphine tolerance at spinal level in rats. This study may provide an idea for producing a novel adjuvant for morphine treatment.
Copyright © 2012 Elsevier B.V. All rights reserved.
Similar articles
-
Antisense oligonucleotide knockdown of mGlu₅ receptor attenuates the antinociceptive tolerance and up-regulated expression of spinal protein kinase C associated with chronic morphine treatment.Eur J Pharmacol. 2012 May 15;683(1-3):78-85. doi: 10.1016/j.ejphar.2012.02.046. Epub 2012 Mar 12. Eur J Pharmacol. 2012. PMID: 22429573
-
Role of G(i)alpha2-protein in opioid tolerance and mu-opioid receptor downregulation in vivo.Synapse. 2003 Feb;47(2):109-16. doi: 10.1002/syn.10149. Synapse. 2003. PMID: 12454948
-
Attenuation of morphine tolerance after antisense oligonucleotide knock-down of spinal mGluR1.Br J Pharmacol. 2002 Jul;136(6):865-72. doi: 10.1038/sj.bjp.0704792. Br J Pharmacol. 2002. PMID: 12110611 Free PMC article.
-
Inhibitory effect of spinal mGlu(5) receptor antisense oligonucleotide on the up-regulated expression of spinal G protein associated with chronic morphine treatment.Eur J Pharmacol. 2014 Jan 15;723:253-8. doi: 10.1016/j.ejphar.2013.11.024. Epub 2013 Dec 1. Eur J Pharmacol. 2014. PMID: 24296320
-
Lipoxin A4 analog attenuates morphine antinociceptive tolerance, withdrawal-induced hyperalgesia, and glial reaction and cytokine expression in the spinal cord of rat.Neuroscience. 2012 Apr 19;208:1-10. doi: 10.1016/j.neuroscience.2012.02.009. Epub 2012 Feb 14. Neuroscience. 2012. PMID: 22366510
Cited by
-
Distinct terminal and cell body mechanisms in the nociceptor mediate hyperalgesic priming.J Neurosci. 2015 Apr 15;35(15):6107-16. doi: 10.1523/JNEUROSCI.5085-14.2015. J Neurosci. 2015. PMID: 25878283 Free PMC article.
-
Systemic Morphine Produces Dose-dependent Nociceptor-mediated Biphasic Changes in Nociceptive Threshold and Neuroplasticity.Neuroscience. 2019 Feb 1;398:64-75. doi: 10.1016/j.neuroscience.2018.11.051. Epub 2018 Dec 7. Neuroscience. 2019. PMID: 30529265 Free PMC article.
-
Contribution of G-Protein α-Subunits to Analgesia, Hyperalgesia, and Hyperalgesic Priming Induced by Subanalgesic and Analgesic Doses of Fentanyl and Morphine.J Neurosci. 2022 Feb 16;42(7):1196-1210. doi: 10.1523/JNEUROSCI.1982-21.2021. Epub 2021 Dec 29. J Neurosci. 2022. PMID: 34965973 Free PMC article.
-
G-protein-coupled estrogen receptor 30 regulation of signaling downstream of protein kinase Cε mediates sex dimorphism in hyaluronan-induced antihyperalgesia.Pain. 2025 Mar 1;166(3):539-556. doi: 10.1097/j.pain.0000000000003419. Epub 2024 Oct 10. Pain. 2025. PMID: 39787533
-
Role of nociceptor αCaMKII in transition from acute to chronic pain (hyperalgesic priming) in male and female rats.J Neurosci. 2013 Jul 3;33(27):11002-11. doi: 10.1523/JNEUROSCI.1785-13.2013. J Neurosci. 2013. PMID: 23825405 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources